Pub Date : 2024-10-11DOI: 10.1186/s12885-024-13009-8
Augustin Nzitakera, Delphine Uwamariya, Hisami Kato, Jean Bosco Surwumwe, André Mbonigaba, Ella Larissa Ndoricyimpaye, Schifra Uwamungu, Felix Manirakiza, Marie Claire Ndayisaba, Gervais Ntakirutimana, Benoit Seminega, Vincent Dusabejambo, Eric Rutaganda, Placide Kamali, François Ngabonziza, Rei Ishikawa, Hirofumi Watanabe, Belson Rugwizangoga, Satoshi Baba, Hidetaka Yamada, Katsuhiro Yoshimura, Yasuhiro Sakai, Haruhiko Sugimura, Kazuya Shinmura
Background: Mutations in the TP53 tumor suppressor gene are well-established drivers of colorectal cancer (CRC) development. However, data on the prevalence of TP53 variants and their association with consensus molecular subtype (CMS) classification in patients with CRC from Rwanda are currently lacking. This study addressed this knowledge gap by investigating TP53 mutation status concerning CMS classification in a CRC cohort from Rwanda.
Methods: Formalin-fixed paraffin-embedded (FFPE) tissue blocks were obtained from 51 patients with CRC at the University Teaching Hospital of Kigali, Rwanda. Exons 4 to 11 and their flanking intron-exon boundaries in the TP53 gene were sequenced using Sanger sequencing to identify potential variants. The recently established immunohistochemistry-based classifier was employed to determine the CMS of each tumor.
Results: Sequencing analysis of cancerous tissue DNA revealed TP53 pathogenic variants in 23 of 51 (45.1%) patients from Rwanda. These variants were predominantly missense types (18/23, 78.3%). The most frequent were c.455dup (p.P153Afs*28), c.524G > A (p.R175H), and c.733G > A (p.G245S), each identified in three tumors. Trinucleotide sequence context analysis of the 23 mutations (20 of which were single-base substitutions) revealed a predominance of the [C > N] pattern among single-base substitutions (SBSs) (18/20; 90.0%), with C[C > T]G being the most frequent mutation (5/18, 27.8%). Furthermore, pyrimidine bases (C and T) were preferentially found at the 5' flanking position of the mutated cytosine (13/18; 72.2%). Analysis of CMS subtypes revealed the following distribution: CMS1 (microsatellite instability-immune) (6/51, 11.8%), CMS2 (canonical) (28/51, 54.9%), CMS3 (metabolic) (9/51, 17.6%), and CMS4 (mesenchymal) (8/51, 15.7%). Interestingly, the majority of TP53 variants were in the CMS2 subgroup (14/23; 60.1%).
Conclusion: Our findings indicate a high frequency of TP53 variants in CRC patients from Rwanda. Importantly, these variants are enriched in the CMS2 subtype. This study, representing the second investigation into molecular alterations in patients with CRC from Rwanda and the first to explore TP53 mutations and CMS classification, provides valuable insights into the molecular landscape of CRC in this understudied population.
{"title":"TP53 mutation status and consensus molecular subtypes of colorectal cancer in patients from Rwanda.","authors":"Augustin Nzitakera, Delphine Uwamariya, Hisami Kato, Jean Bosco Surwumwe, André Mbonigaba, Ella Larissa Ndoricyimpaye, Schifra Uwamungu, Felix Manirakiza, Marie Claire Ndayisaba, Gervais Ntakirutimana, Benoit Seminega, Vincent Dusabejambo, Eric Rutaganda, Placide Kamali, François Ngabonziza, Rei Ishikawa, Hirofumi Watanabe, Belson Rugwizangoga, Satoshi Baba, Hidetaka Yamada, Katsuhiro Yoshimura, Yasuhiro Sakai, Haruhiko Sugimura, Kazuya Shinmura","doi":"10.1186/s12885-024-13009-8","DOIUrl":"10.1186/s12885-024-13009-8","url":null,"abstract":"<p><strong>Background: </strong>Mutations in the TP53 tumor suppressor gene are well-established drivers of colorectal cancer (CRC) development. However, data on the prevalence of TP53 variants and their association with consensus molecular subtype (CMS) classification in patients with CRC from Rwanda are currently lacking. This study addressed this knowledge gap by investigating TP53 mutation status concerning CMS classification in a CRC cohort from Rwanda.</p><p><strong>Methods: </strong>Formalin-fixed paraffin-embedded (FFPE) tissue blocks were obtained from 51 patients with CRC at the University Teaching Hospital of Kigali, Rwanda. Exons 4 to 11 and their flanking intron-exon boundaries in the TP53 gene were sequenced using Sanger sequencing to identify potential variants. The recently established immunohistochemistry-based classifier was employed to determine the CMS of each tumor.</p><p><strong>Results: </strong>Sequencing analysis of cancerous tissue DNA revealed TP53 pathogenic variants in 23 of 51 (45.1%) patients from Rwanda. These variants were predominantly missense types (18/23, 78.3%). The most frequent were c.455dup (p.P153Afs*28), c.524G > A (p.R175H), and c.733G > A (p.G245S), each identified in three tumors. Trinucleotide sequence context analysis of the 23 mutations (20 of which were single-base substitutions) revealed a predominance of the [C > N] pattern among single-base substitutions (SBSs) (18/20; 90.0%), with C[C > T]G being the most frequent mutation (5/18, 27.8%). Furthermore, pyrimidine bases (C and T) were preferentially found at the 5' flanking position of the mutated cytosine (13/18; 72.2%). Analysis of CMS subtypes revealed the following distribution: CMS1 (microsatellite instability-immune) (6/51, 11.8%), CMS2 (canonical) (28/51, 54.9%), CMS3 (metabolic) (9/51, 17.6%), and CMS4 (mesenchymal) (8/51, 15.7%). Interestingly, the majority of TP53 variants were in the CMS2 subgroup (14/23; 60.1%).</p><p><strong>Conclusion: </strong>Our findings indicate a high frequency of TP53 variants in CRC patients from Rwanda. Importantly, these variants are enriched in the CMS2 subtype. This study, representing the second investigation into molecular alterations in patients with CRC from Rwanda and the first to explore TP53 mutations and CMS classification, provides valuable insights into the molecular landscape of CRC in this understudied population.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Angiogenesis is associated with tumour growth, infiltration, and metastasis. This study aimed to detect the mechanisms of angiogenesis-related genes (ARGs) in multiple myeloma (MM) and to construct a new prognostic model.
Methods: MM research foundation (MMRF)-CoMMpass cohort, GSE47552, GSE57317, and ARGs were sourced from public databases. Differentially expressed genes (DEGs) in the tumour and control cohorts in GSE47552 were determined through differential expression analysis and were enriched with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Weighted gene coexpression network analysis (WGCNA) was applied to derive modules linked to the ARG scores and obtain module genes in GSE47552. Differentially expressed ARGs (DE-ARGs) were selected for subsequent analyses by overlapping DEGs and module genes. Furthermore, prognostic genes were selected using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. Depending on the prognostic genes, a risk model was constructed, and risk scores were determined. Moreover, MM samples from MMRF-CoMMpass were sorted into high- and low-risk teams on account of the median risk score. Additionally, correlations among clinical characteristics, gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), immune analysis, immunotherapy predictions and the mRNA‒miRNA‒lncRNA network were carried out.
Results: A total of 898 DEGs, 211 module genes, 24 DE-ARGs and three prognostic genes (AKAP12, C11orf80 and EMP1) were selected for this study. Enrichment analysis revealed that the DEGs were related to 86 GO terms, such as 'cytoplasmic translation', and 41 KEGG pathways, such as 'small cell lung cancer'. A prognostic gene-based risk model was created in MMRF-CoMMpass and confirmed with the GSE57317 dataset. Moreover, a nomogram was established on the basis of independent prognostic factors that have proven to be good predictors. In addition, the immune cell infiltration results suggested that memory B cells were enriched in the high-risk group and that immature B cells were enriched in the low-risk group. Finally, the mRNA‒miRNA‒lncRNA network demonstrated that hsa-miR-508-5p was tightly associated with EMP1 and AKAP12. RT‒qPCR was used to validate the expression of the genes associated with prognosis.
Conclusion: A new prognostic model of MM associated with ARGs was created and validated, providing a new perspective for exploring the connection between ARGs and MM.
背景:血管生成与肿瘤的生长、浸润和转移有关。本研究旨在检测多发性骨髓瘤(MM)中血管生成相关基因(ARGs)的机制,并构建一个新的预后模型:方法:MM研究基金会(MMRF)-CoMMpass队列、GSE47552、GSE57317和ARGs均来自公共数据库。通过差异表达分析确定了GSE47552中肿瘤队列和对照队列中的差异表达基因(DEGs),并通过基因本体(GO)和京都基因与基因组百科全书(KEGG)分析进行了富集。应用加权基因共表达网络分析(WGCNA)得出与 ARG 评分相关的模块,并获得 GSE47552 中的模块基因。通过重叠的 DEGs 和模块基因,筛选出差异表达的 ARGs(DE-ARGs)用于后续分析。此外,还利用单变量 Cox 和最小绝对收缩和选择算子(LASSO)回归分析筛选出了预后基因。根据预后基因构建了风险模型,并确定了风险评分。此外,MMRF-CoMMpass 中的 MM 样本根据中位风险评分分为高风险和低风险组。此外,还进行了临床特征、基因组变异分析(GSVA)、基因组富集分析(GSEA)、免疫分析、免疫疗法预测和mRNA-miRNA-lncRNA网络之间的相关性分析:本研究共筛选出898个DEGs、211个模块基因、24个DE-ARGs和3个预后基因(AKAP12、C11orf80和EMP1)。富集分析表明,这些 DEGs 与 86 个 GO 术语(如 "细胞质翻译")和 41 个 KEGG 通路(如 "小细胞肺癌")相关。在 MMRF-CoMMpass 中建立了基于预后基因的风险模型,并通过 GSE57317 数据集进行了确认。此外,还根据已被证明具有良好预测作用的独立预后因素建立了一个提名图。此外,免疫细胞浸润结果表明,记忆 B 细胞富集于高风险组,而未成熟 B 细胞富集于低风险组。最后,mRNA-miRNA-lncRNA 网络显示,hsa-miR-508-5p 与 EMP1 和 AKAP12 紧密相关。RT-qPCR用于验证预后相关基因的表达:结论:建立并验证了与ARGs相关的MM新预后模型,为探索ARGs与MM之间的联系提供了新的视角。
{"title":"Construction and validation of a prognostic model of angiogenesis-related genes in multiple myeloma.","authors":"Rui Hu, Fengyu Chen, Xueting Yu, Zengzheng Li, Yujin Li, Shuai Feng, Jianqiong Liu, Huiyuan Li, Chengmin Shen, Xuezhong Gu, Zhixiang Lu","doi":"10.1186/s12885-024-13024-9","DOIUrl":"10.1186/s12885-024-13024-9","url":null,"abstract":"<p><strong>Background: </strong>Angiogenesis is associated with tumour growth, infiltration, and metastasis. This study aimed to detect the mechanisms of angiogenesis-related genes (ARGs) in multiple myeloma (MM) and to construct a new prognostic model.</p><p><strong>Methods: </strong>MM research foundation (MMRF)-CoMMpass cohort, GSE47552, GSE57317, and ARGs were sourced from public databases. Differentially expressed genes (DEGs) in the tumour and control cohorts in GSE47552 were determined through differential expression analysis and were enriched with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Weighted gene coexpression network analysis (WGCNA) was applied to derive modules linked to the ARG scores and obtain module genes in GSE47552. Differentially expressed ARGs (DE-ARGs) were selected for subsequent analyses by overlapping DEGs and module genes. Furthermore, prognostic genes were selected using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. Depending on the prognostic genes, a risk model was constructed, and risk scores were determined. Moreover, MM samples from MMRF-CoMMpass were sorted into high- and low-risk teams on account of the median risk score. Additionally, correlations among clinical characteristics, gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), immune analysis, immunotherapy predictions and the mRNA‒miRNA‒lncRNA network were carried out.</p><p><strong>Results: </strong>A total of 898 DEGs, 211 module genes, 24 DE-ARGs and three prognostic genes (AKAP12, C11orf80 and EMP1) were selected for this study. Enrichment analysis revealed that the DEGs were related to 86 GO terms, such as 'cytoplasmic translation', and 41 KEGG pathways, such as 'small cell lung cancer'. A prognostic gene-based risk model was created in MMRF-CoMMpass and confirmed with the GSE57317 dataset. Moreover, a nomogram was established on the basis of independent prognostic factors that have proven to be good predictors. In addition, the immune cell infiltration results suggested that memory B cells were enriched in the high-risk group and that immature B cells were enriched in the low-risk group. Finally, the mRNA‒miRNA‒lncRNA network demonstrated that hsa-miR-508-5p was tightly associated with EMP1 and AKAP12. RT‒qPCR was used to validate the expression of the genes associated with prognosis.</p><p><strong>Conclusion: </strong>A new prognostic model of MM associated with ARGs was created and validated, providing a new perspective for exploring the connection between ARGs and MM.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-11DOI: 10.1186/s12885-024-13025-8
Ling Wang, Meixin Zhen, Lulu Liao, Hui Li, Huang Yan, James A Wiley, Qing Lu, Xuemei Chen, Jun Yv, Boni Ding
Background: Understanding the factors that contribute to variability in breast cancer-related lymphedema (BCRL) is an important first step in developing targeted interventions to improve quality of life in breast cancer patients. Although previous research studies have has identified many risk factors for BCRL, dietary habits and catheterization type have rarely been studied until the present.
Aim: This study aims to explore the effects of nursing factors such as dietary habits and catheterization type on breast cancer-related lymphedema (BCRL).
Methods: This retrospective cohort study included 1,476 breast cancer patients who underwent surgery between January 1, 2012, and September 1, 2020. Lymphedema was assessed with a validated self-report questionnaire. All research data were obtained from medical records and a follow-up database. Multivariate Cox regression was conducted to explore the effects of dietary habits and catheterization type on BCRL.
Results: The results showed an increased risk for BCRL among breast cancer patients who followed a high-fat diet prehospitalization (HR = 2.47; 95% CI = 1.55-3.94; P < 0.001), indwelling totally implantable venous access ports (TIVAPs) compared with indwelling needles (HR = 0.56; 95% CI = 0.35-0.90;P = 0.017) or indwelling peripherally inserted central catheters (PICCs) (HR = 0.69; 95% CI = 0.45-1.05; P = 0.086).
Conclusion: High-fat diet pre-hospitalization was an independent risk factor for lymphedema. The TIVAPs did not exert a protective effect on lymphedema compared with the PICC and indwelling needle. This study finding offers new insights to develop targeted interventions to decrease the incidence of lymphedema.
{"title":"Effects of dietary habits and catheterization type on breast cancer-related lymphedema: a retrospective cohort study.","authors":"Ling Wang, Meixin Zhen, Lulu Liao, Hui Li, Huang Yan, James A Wiley, Qing Lu, Xuemei Chen, Jun Yv, Boni Ding","doi":"10.1186/s12885-024-13025-8","DOIUrl":"10.1186/s12885-024-13025-8","url":null,"abstract":"<p><strong>Background: </strong>Understanding the factors that contribute to variability in breast cancer-related lymphedema (BCRL) is an important first step in developing targeted interventions to improve quality of life in breast cancer patients. Although previous research studies have has identified many risk factors for BCRL, dietary habits and catheterization type have rarely been studied until the present.</p><p><strong>Aim: </strong>This study aims to explore the effects of nursing factors such as dietary habits and catheterization type on breast cancer-related lymphedema (BCRL).</p><p><strong>Methods: </strong>This retrospective cohort study included 1,476 breast cancer patients who underwent surgery between January 1, 2012, and September 1, 2020. Lymphedema was assessed with a validated self-report questionnaire. All research data were obtained from medical records and a follow-up database. Multivariate Cox regression was conducted to explore the effects of dietary habits and catheterization type on BCRL.</p><p><strong>Results: </strong>The results showed an increased risk for BCRL among breast cancer patients who followed a high-fat diet prehospitalization (HR = 2.47; 95% CI = 1.55-3.94; P < 0.001), indwelling totally implantable venous access ports (TIVAPs) compared with indwelling needles (HR = 0.56; 95% CI = 0.35-0.90;P = 0.017) or indwelling peripherally inserted central catheters (PICCs) (HR = 0.69; 95% CI = 0.45-1.05; P = 0.086).</p><p><strong>Conclusion: </strong>High-fat diet pre-hospitalization was an independent risk factor for lymphedema. The TIVAPs did not exert a protective effect on lymphedema compared with the PICC and indwelling needle. This study finding offers new insights to develop targeted interventions to decrease the incidence of lymphedema.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-11DOI: 10.1186/s12885-024-12977-1
Hana Hemead, Rania Gaber Aly, Mostafa Kotb, Ahmed Abdelaziz
Background: Pleuropulmonary Blastoma (PPB) is an extremely uncommon, highly aggressive tumor that arises from either the lungs or pleura. According to Dehner, PPB was classified into three groups: type I (cystic), type II (mixed), and type III (solid). Type I tends to occur more commonly in infants and has a more favorable prognosis compared to types II and III. This tumor is very rare in pediatric age group; hence, there is no consensus on the optimal treatment regimen for it to date. Type I tumors, which resemble congenital lung cysts, can eventually progress to more aggressive type II and type III tumors. This article aims to increase general awareness of this pathology, clinical presentation, and differential diagnosis in order to identify this rare entity early in its course. By presenting 4 such cases, we highlight that PPB can be missed early in diagnosis and it is important to be alert when putting this rare tumor in differential diagnosis of cystic lung lesions.
Methods: A retrospective study was conducted between 2015 and 2020 involving patients who had a definitive diagnosis of PPB with emphasis on clinical presentation, preoperative imaging studies, intra-operative findings, pathological reports, ancillary treatment, and outcomes. All patients were followed up every 6 months to monitor local recurrence and distant metastasis by undergoing physical exam and non-contrast enhanced CT of the chest. The primary outcome is to identify the mortality and morbidity (recurrence and distant metastasis) of PPB for cases admitted in our institute.
Results: Four children were diagnosed with PPB during the study period. Clinically, patients presented with manifestations ranging from respiratory distress, fever to obstructive shock and radiologically, 2 cases were presented with mediastinal mass and the other 2 presented with pneumothorax. Regrettably, none of the cases were diagnosed pre-operatively. One lesion proved to be type I, 2 were type II and one was type III. All cases underwent chemotherapy using the combination of vincristine, Adriamycin and cyclophosphamide (VAC regimen). Recurrence was detected in a type II case, around 2 years after operation, and the other type II case developed brain metastasis that was discovered 3 years after operation. Type I case showed no local or distant metastasis.
Conclusion: A prompt preoperative diagnosis and workup of cases of PPB is crucial to enable optimal intervention intraoperatively and early postoperative treatment. Though it is uncommon, PPB should be considered in the differential diagnosis of cystic lung lesions.
背景:胸膜肺母细胞瘤(PPB胸膜肺母细胞瘤(PPB)是一种极为罕见、侵袭性极强的肿瘤,可发生于肺部或胸膜。根据 Dehner 的观点,PPB 可分为三类:I 型(囊性)、II 型(混合型)和 III 型(实性)。I 型多见于婴儿,与 II 型和 III 型相比,预后较好。这种肿瘤在儿童年龄组中非常罕见,因此迄今为止还没有就其最佳治疗方案达成共识。I 型肿瘤类似于先天性肺囊肿,最终会发展为侵袭性更强的 II 型和 III 型肿瘤。本文旨在提高人们对这种病理学、临床表现和鉴别诊断的普遍认识,以便在病程早期发现这种罕见的实体瘤。通过介绍4例此类病例,我们强调PPB在早期诊断时可能会被漏诊,因此在将这种罕见肿瘤纳入肺囊性病变的鉴别诊断时必须提高警惕:我们在2015年至2020年期间开展了一项回顾性研究,涉及明确诊断为PPB的患者,研究重点包括临床表现、术前影像学检查、术中发现、病理报告、辅助治疗和预后。所有患者每 6 个月随访一次,通过体格检查和胸部非对比增强 CT 监测局部复发和远处转移。主要结果是确定我院收治的 PPB 病例的死亡率和发病率(复发和远处转移):研究期间有四名儿童被确诊为 PPB。临床表现包括呼吸困难、发热和阻塞性休克,放射学检查中,2 例出现纵隔肿块,另外 2 例出现气胸。遗憾的是,所有病例均未在术前确诊。一个病例被证实为 I 型,两个为 II 型,一个为 III 型。所有病例都接受了长春新碱、阿霉素和环磷酰胺联合化疗(VAC 方案)。一个 II 型病例在术后 2 年左右发现复发,另一个 II 型病例在术后 3 年发现脑转移。I型病例没有出现局部或远处转移:结论:对 PPB 病例进行及时的术前诊断和检查对于实现术中最佳干预和术后早期治疗至关重要。尽管 PPB 并不常见,但仍应在肺部囊性病变的鉴别诊断中予以考虑。
{"title":"Pediatric pleuropulmonary blastoma: analysis of four cases.","authors":"Hana Hemead, Rania Gaber Aly, Mostafa Kotb, Ahmed Abdelaziz","doi":"10.1186/s12885-024-12977-1","DOIUrl":"10.1186/s12885-024-12977-1","url":null,"abstract":"<p><strong>Background: </strong>Pleuropulmonary Blastoma (PPB) is an extremely uncommon, highly aggressive tumor that arises from either the lungs or pleura. According to Dehner, PPB was classified into three groups: type I (cystic), type II (mixed), and type III (solid). Type I tends to occur more commonly in infants and has a more favorable prognosis compared to types II and III. This tumor is very rare in pediatric age group; hence, there is no consensus on the optimal treatment regimen for it to date. Type I tumors, which resemble congenital lung cysts, can eventually progress to more aggressive type II and type III tumors. This article aims to increase general awareness of this pathology, clinical presentation, and differential diagnosis in order to identify this rare entity early in its course. By presenting 4 such cases, we highlight that PPB can be missed early in diagnosis and it is important to be alert when putting this rare tumor in differential diagnosis of cystic lung lesions.</p><p><strong>Methods: </strong>A retrospective study was conducted between 2015 and 2020 involving patients who had a definitive diagnosis of PPB with emphasis on clinical presentation, preoperative imaging studies, intra-operative findings, pathological reports, ancillary treatment, and outcomes. All patients were followed up every 6 months to monitor local recurrence and distant metastasis by undergoing physical exam and non-contrast enhanced CT of the chest. The primary outcome is to identify the mortality and morbidity (recurrence and distant metastasis) of PPB for cases admitted in our institute.</p><p><strong>Results: </strong>Four children were diagnosed with PPB during the study period. Clinically, patients presented with manifestations ranging from respiratory distress, fever to obstructive shock and radiologically, 2 cases were presented with mediastinal mass and the other 2 presented with pneumothorax. Regrettably, none of the cases were diagnosed pre-operatively. One lesion proved to be type I, 2 were type II and one was type III. All cases underwent chemotherapy using the combination of vincristine, Adriamycin and cyclophosphamide (VAC regimen). Recurrence was detected in a type II case, around 2 years after operation, and the other type II case developed brain metastasis that was discovered 3 years after operation. Type I case showed no local or distant metastasis.</p><p><strong>Conclusion: </strong>A prompt preoperative diagnosis and workup of cases of PPB is crucial to enable optimal intervention intraoperatively and early postoperative treatment. Though it is uncommon, PPB should be considered in the differential diagnosis of cystic lung lesions.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-11DOI: 10.1186/s12885-024-12989-x
Lan Feng, Qun Shi, Shujuan Wang, Ye Zhao, Haiyan Wu, Lei Wei, Qing Hao, Zhaojun Cui, Lin Wang, Jing Zhang, Dan Zhang, Xinxin Zhan, Jingwen Jiang
Objective: Immune checkpoint inhibitor (ICI) therapy activates the immune system to recognize and eliminate cancer cells that have escaped surveillance. This study aimed to compare the treatment outcome of advanced and recurrent cervical cancer patients treated with first-line platinum and paclitaxel with or without ICI.
Methods: Data from 69 advanced and recurrent cervical cancer patients treated with first-line ICI plus platinum and paclitaxel (N = 33) or first-line platinum and paclitaxel (N = 36) were reviewed between March 2020 and January 2023 in this retrospective study. Patients chose treatment based on the actual disease condition, patient willingness, and medical advice. Additionally, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were calculated, and adverse events were gained.
Results: There was no difference in baseline data between patients receiving the two different treatments (all P > 0.05). Complete response rate (18.2% vs. 8.3%; P = 0.294), ORR (48.5% vs. 30.6%; P = 0.127), and DCR (81.8% vs. 72.2%; P = 0.345) tended to ascend in patients treated with ICI plus platinum and paclitaxel compared to those treated with platinum and paclitaxel, although there was no statistical significance. In patients treated with ICI plus platinum and paclitaxel, the median PFS was 10.3 months and the median OS was not reached. Meanwhile, the median PFS and OS were 7.7 and 16.9 months in patients treated with platinum and paclitaxel. PFS (P = 0.036) and OS (P = 0.033) were increased in patients treated with ICI plus platinum and paclitaxel versus those treated with platinum and paclitaxel, which was verified by multivariate Cox regression analyses (both P < 0.05). No difference was observed in the occurrence of adverse events between patients receiving the two different treatments (all P > 0.05).
Conclusion: First-line ICI plus platinum and paclitaxel yields better treatment responses, longer survival, and non-differential adverse events versus first-line platinum and paclitaxel in advanced and recurrent cervical cancer patients.
目的:免疫检查点抑制剂(ICI)疗法可激活免疫系统,识别并消除逃避监控的癌细胞。本研究旨在比较接受一线铂类和紫杉醇治疗的晚期和复发性宫颈癌患者接受 ICI 或不接受 ICI 治疗的疗效:在这项回顾性研究中,回顾了2020年3月至2023年1月期间接受一线ICI加铂类和紫杉醇(33例)或一线铂类和紫杉醇(36例)治疗的69例晚期和复发性宫颈癌患者的数据。患者根据实际病情、患者意愿和医嘱选择治疗方法。此外,还计算了客观反应率(ORR)、疾病控制率(DCR)、无进展生存期(PFS)和总生存期(OS),并获得了不良事件:结果:接受两种不同治疗方法的患者在基线数据上没有差异(P>0.05)。与接受铂类和紫杉醇治疗的患者相比,接受ICI加铂类和紫杉醇治疗的患者的完全反应率(18.2% vs. 8.3%;P = 0.294)、ORR(48.5% vs. 30.6%;P = 0.127)和DCR(81.8% vs. 72.2%;P = 0.345)呈上升趋势,但无统计学意义。在接受 ICI 加铂和紫杉醇治疗的患者中,中位 PFS 为 10.3 个月,中位 OS 未达到。与此同时,接受铂和紫杉醇治疗的患者的中位 PFS 和 OS 分别为 7.7 个月和 16.9 个月。ICI联合铂类和紫杉醇治疗患者的PFS(P = 0.036)和OS(P = 0.033)较铂类和紫杉醇治疗患者有所增加,多变量Cox回归分析证实了这一点(均为P 0.05):结论:在晚期和复发性宫颈癌患者中,一线 ICI 加铂和紫杉醇与一线铂和紫杉醇相比,可获得更好的治疗反应、更长的生存期和无差异的不良反应。
{"title":"The outcome of advanced and recurrent cervical cancer patients treated with first-line platinum and paclitaxel with or without indication for immune checkpoint inhibitors: the comparative study.","authors":"Lan Feng, Qun Shi, Shujuan Wang, Ye Zhao, Haiyan Wu, Lei Wei, Qing Hao, Zhaojun Cui, Lin Wang, Jing Zhang, Dan Zhang, Xinxin Zhan, Jingwen Jiang","doi":"10.1186/s12885-024-12989-x","DOIUrl":"10.1186/s12885-024-12989-x","url":null,"abstract":"<p><strong>Objective: </strong>Immune checkpoint inhibitor (ICI) therapy activates the immune system to recognize and eliminate cancer cells that have escaped surveillance. This study aimed to compare the treatment outcome of advanced and recurrent cervical cancer patients treated with first-line platinum and paclitaxel with or without ICI.</p><p><strong>Methods: </strong>Data from 69 advanced and recurrent cervical cancer patients treated with first-line ICI plus platinum and paclitaxel (N = 33) or first-line platinum and paclitaxel (N = 36) were reviewed between March 2020 and January 2023 in this retrospective study. Patients chose treatment based on the actual disease condition, patient willingness, and medical advice. Additionally, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were calculated, and adverse events were gained.</p><p><strong>Results: </strong>There was no difference in baseline data between patients receiving the two different treatments (all P > 0.05). Complete response rate (18.2% vs. 8.3%; P = 0.294), ORR (48.5% vs. 30.6%; P = 0.127), and DCR (81.8% vs. 72.2%; P = 0.345) tended to ascend in patients treated with ICI plus platinum and paclitaxel compared to those treated with platinum and paclitaxel, although there was no statistical significance. In patients treated with ICI plus platinum and paclitaxel, the median PFS was 10.3 months and the median OS was not reached. Meanwhile, the median PFS and OS were 7.7 and 16.9 months in patients treated with platinum and paclitaxel. PFS (P = 0.036) and OS (P = 0.033) were increased in patients treated with ICI plus platinum and paclitaxel versus those treated with platinum and paclitaxel, which was verified by multivariate Cox regression analyses (both P < 0.05). No difference was observed in the occurrence of adverse events between patients receiving the two different treatments (all P > 0.05).</p><p><strong>Conclusion: </strong>First-line ICI plus platinum and paclitaxel yields better treatment responses, longer survival, and non-differential adverse events versus first-line platinum and paclitaxel in advanced and recurrent cervical cancer patients.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: This study aims to investigate how the impact of preoperative sarcopenia and inflammatory markers for laryngeal cancer patients and develop a new scoring system to predict their prognosis.
Materials and methods: Patients who underwent laryngectomy for laryngeal cancer (LC) from December 2015 to December 2020 at the Second Affiliated Hospital of Fujian Medical University were included. Independent prognostic factors were determined using univariate and multivariate analyses. A new scoring system (SFAR) was established based on FAR and preoperative sarcopenia, and statistically analyzed.
Results: 198 cases included in this study that met the admission criteria. Multivariate analysis shown that preoperative sarcopenia, pTNM stage, and FAR were independent prognostic factors for laryngeal cancer. Based on these three indicators, we developed the SFAR scoring system. Multivariate analysis showed that SFAR was an independent predictor of laryngeal cancer (p < 0.001). SFAR was then incorporated into a prognostic model that included T-stage and N-stage, and a column-line graph was generated to accurately predict its survival.
Conclusion: Systemic inflammation and sarcopenia are significantly associated with postoperative prognosis in laryngeal cancer. A new scoring system (SFAR) had implications for improving the prognosis of patients undergoing surgery for laryngeal cancer.
{"title":"Study of the significance of the combination of the fibrinogen-albumin ratio and sarcopenia in predicting the prognosis of laryngeal cancer patients undergoing radical surgery.","authors":"Yizheng Zhang, Zhiyong Meng, Ming Lu, Shenjiong Ruan, Jiao Zhou, Mingchen Zhang, Yanjun Huang, Kehui Chen, Xinyuan Luo, Cheng-Ke Xie, Chaohui Zheng","doi":"10.1186/s12885-024-13039-2","DOIUrl":"10.1186/s12885-024-13039-2","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to investigate how the impact of preoperative sarcopenia and inflammatory markers for laryngeal cancer patients and develop a new scoring system to predict their prognosis.</p><p><strong>Materials and methods: </strong>Patients who underwent laryngectomy for laryngeal cancer (LC) from December 2015 to December 2020 at the Second Affiliated Hospital of Fujian Medical University were included. Independent prognostic factors were determined using univariate and multivariate analyses. A new scoring system (SFAR) was established based on FAR and preoperative sarcopenia, and statistically analyzed.</p><p><strong>Results: </strong>198 cases included in this study that met the admission criteria. Multivariate analysis shown that preoperative sarcopenia, pTNM stage, and FAR were independent prognostic factors for laryngeal cancer. Based on these three indicators, we developed the SFAR scoring system. Multivariate analysis showed that SFAR was an independent predictor of laryngeal cancer (p < 0.001). SFAR was then incorporated into a prognostic model that included T-stage and N-stage, and a column-line graph was generated to accurately predict its survival.</p><p><strong>Conclusion: </strong>Systemic inflammation and sarcopenia are significantly associated with postoperative prognosis in laryngeal cancer. A new scoring system (SFAR) had implications for improving the prognosis of patients undergoing surgery for laryngeal cancer.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Gliomas are the highly aggressive brain tumor and also the most devastating human tumors. The latent TGF binding proteins (LTBP) had been found to be involved in malignant biological process and could be used as potent biomarkers in several solid tumors. While the role of LTBP family in human glioma remain to be elucidated.
Methods: Normalized gene expression and corresponding clinical data of 2407 gliomas samples in public datasets were downloaded from Gliovis. Kaplan-Meier methods and Cox regression analysis was used for survival analyses.Western blot (WB) and Immunohistochemical (IHC) testing were employed to test LTBPs protein level in 154 gliomas samples. Correlation between LTBP2 expression and immune infiltration was evaluated by immunofluorescence (IF) and IHC in glioma tissues. CCK8 and flow cytometric analysis were used to detect the effect of LTBP2 on glioma cells. Orthotopic glioma- mouse models were utilized to evaluate effects in vivo.
Results: LTBP2 mRNA level was dramatically higher in glioma samples compared with non-tumor brain tissues in XENA-TCGA_GTEx, Gill and Gravendeel datasets (all P < 0.01), and its expression positively correlated with glioma WHO grade, IDH1/2 wildtype and mesenchymal subtypes. These results were confirmed by In-house cohort which was detected by WB and IHC. We found that gliomas patients with high LTBP2 level had shorter OS than those with low LTBP2 level. LTBP2 expression significantly associated with glioma immune score (Spearman r = 0.68, P < 0.01)) and strongly correlated with infiltration degreee of macrophages both in lower grade gliomas (LGG) and GBM. Knocking down LTBP2 obviously reduced proliferation and enhanced sensitivity to temozolomide in U87 and U251 cells. Nude mice with lower expression of LTBP2 had slower tumor growth, and accompanied by less tumor-associated macrophages (TAMs) infiltration detected by IHC staining in vivo. Finally, low LTBP2 expression glioma patients who received chemotherapy survived longer than patients with high LTBP2 expression.
Conclusion: LTBP2 could be used as a prognostic marker, and high LTBP2 expression related to abundant TAMs infiltration and with a worse response to chemotherapy.
{"title":"Integrated bioinformatics analysis and experimental validation on malignant progression and immune cell infiltration of LTBP2 in gliomas.","authors":"Lun Gao, Rui Zhang, Wenbin Zhang, Yanfang Lan, Xiangpan Li, Qiang Cai, Junhui Liu","doi":"10.1186/s12885-024-12976-2","DOIUrl":"10.1186/s12885-024-12976-2","url":null,"abstract":"<p><strong>Background: </strong>Gliomas are the highly aggressive brain tumor and also the most devastating human tumors. The latent TGF binding proteins (LTBP) had been found to be involved in malignant biological process and could be used as potent biomarkers in several solid tumors. While the role of LTBP family in human glioma remain to be elucidated.</p><p><strong>Methods: </strong>Normalized gene expression and corresponding clinical data of 2407 gliomas samples in public datasets were downloaded from Gliovis. Kaplan-Meier methods and Cox regression analysis was used for survival analyses.Western blot (WB) and Immunohistochemical (IHC) testing were employed to test LTBPs protein level in 154 gliomas samples. Correlation between LTBP2 expression and immune infiltration was evaluated by immunofluorescence (IF) and IHC in glioma tissues. CCK8 and flow cytometric analysis were used to detect the effect of LTBP2 on glioma cells. Orthotopic glioma- mouse models were utilized to evaluate effects in vivo.</p><p><strong>Results: </strong>LTBP2 mRNA level was dramatically higher in glioma samples compared with non-tumor brain tissues in XENA-TCGA_GTEx, Gill and Gravendeel datasets (all P < 0.01), and its expression positively correlated with glioma WHO grade, IDH1/2 wildtype and mesenchymal subtypes. These results were confirmed by In-house cohort which was detected by WB and IHC. We found that gliomas patients with high LTBP2 level had shorter OS than those with low LTBP2 level. LTBP2 expression significantly associated with glioma immune score (Spearman r = 0.68, P < 0.01)) and strongly correlated with infiltration degreee of macrophages both in lower grade gliomas (LGG) and GBM. Knocking down LTBP2 obviously reduced proliferation and enhanced sensitivity to temozolomide in U87 and U251 cells. Nude mice with lower expression of LTBP2 had slower tumor growth, and accompanied by less tumor-associated macrophages (TAMs) infiltration detected by IHC staining in vivo. Finally, low LTBP2 expression glioma patients who received chemotherapy survived longer than patients with high LTBP2 expression.</p><p><strong>Conclusion: </strong>LTBP2 could be used as a prognostic marker, and high LTBP2 expression related to abundant TAMs infiltration and with a worse response to chemotherapy.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1186/s12885-024-13011-0
Aezam Rasekhi Kazeruni, Nahid Babaei, Hadi Esmaeili Gouvarchin Ghaleh, Abbas Doosti, Mahdieh Farzanehpour
Background and aims: Cervical cancer (CC) is a common cancer among women, often treated with Doxorubicin (Doxo). Research is underway to explore the use of oncolytic virus (OV) therapy as a means to improve drug efficacy and enhance the immune system's tumor-fighting capabilities. Hence, our study purposes to evaluate the therapeutic potential of Newcastle disease virus (NDV) in increasing the antitumor efficacy of Doxo in mouse models of CC.
Methods and materials: TC1 cells were administered to C57BL/6 mice (Female) in a range of 6 to 8 weeks age (n = 40) to induce tumor growth. After tumor development, four treatment groups of mice were formed. Treatment were performed through NDV, Doxo, and a combination of both in three groups of treatment twice in a one-week intervention manner, while the control group treated with PBS. Following the last treatment, half of these mice were subjected to euthanize due to the immune-response assessment, and the other half were followed up till they died naturally in a certain period of time.
Results: Mice that underwent the combined treatment showed significantly improved survival rates and slower tumor progression in comparison with the control group. This combined treatment substantially elevated nitric oxide (NO) and lactate dehydrogenase (LDH) levels in the splenocytes cultures of mice bearing cervical tumors. Furthermore, combination therapy resulted in a notable elevation in TNF-α, IL-12, and IFN-γ, secretion alongside a reduction in the release of TGF-β and IL-4 within the splenocytes in counter with the treatment of just NDV or Doxo.
Conclusion: According to the findings of this study, it seems that utilizing NDV can improve the effectiveness of Doxo in a mouse model of CC, suggesting it can serve as an adjunct therapy alongside chemotherapy.
{"title":"Newcastle disease virus enhances the antitumor efficacy of Doxorubicin in a cervical cancer mouse model.","authors":"Aezam Rasekhi Kazeruni, Nahid Babaei, Hadi Esmaeili Gouvarchin Ghaleh, Abbas Doosti, Mahdieh Farzanehpour","doi":"10.1186/s12885-024-13011-0","DOIUrl":"10.1186/s12885-024-13011-0","url":null,"abstract":"<p><strong>Background and aims: </strong>Cervical cancer (CC) is a common cancer among women, often treated with Doxorubicin (Doxo). Research is underway to explore the use of oncolytic virus (OV) therapy as a means to improve drug efficacy and enhance the immune system's tumor-fighting capabilities. Hence, our study purposes to evaluate the therapeutic potential of Newcastle disease virus (NDV) in increasing the antitumor efficacy of Doxo in mouse models of CC.</p><p><strong>Methods and materials: </strong>TC1 cells were administered to C57BL/6 mice (Female) in a range of 6 to 8 weeks age (n = 40) to induce tumor growth. After tumor development, four treatment groups of mice were formed. Treatment were performed through NDV, Doxo, and a combination of both in three groups of treatment twice in a one-week intervention manner, while the control group treated with PBS. Following the last treatment, half of these mice were subjected to euthanize due to the immune-response assessment, and the other half were followed up till they died naturally in a certain period of time.</p><p><strong>Results: </strong>Mice that underwent the combined treatment showed significantly improved survival rates and slower tumor progression in comparison with the control group. This combined treatment substantially elevated nitric oxide (NO) and lactate dehydrogenase (LDH) levels in the splenocytes cultures of mice bearing cervical tumors. Furthermore, combination therapy resulted in a notable elevation in TNF-α, IL-12, and IFN-γ, secretion alongside a reduction in the release of TGF-β and IL-4 within the splenocytes in counter with the treatment of just NDV or Doxo.</p><p><strong>Conclusion: </strong>According to the findings of this study, it seems that utilizing NDV can improve the effectiveness of Doxo in a mouse model of CC, suggesting it can serve as an adjunct therapy alongside chemotherapy.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The increasing problems of drug and radiotherapy resistance in cervical cancer underscores the need for novel methods for its management. Reports indicate that the expression of MPC1 may be associated with the tumor microenvironment and the occurrence of ferroptosis in cervical cancer. The objective of this study was to visually illustrate the prognostic significance and immunological characterization of MPC1 in cervical cancer.
Methods: The expression profile and prognostic significance of MPC1 were analyzed using various databases, including UALCAN, TIMER2, GEPIA2, and Kaplan-Meier Plotter. TISIDB, TIMER2, and immunohistochemical analysis were used to investigate the correlation between MPC1 expression and immune infiltration. GO enrichment analysis, KEGG analysis, Reactome analysis, ConsensusPathDB, and GeneMANIA were used to visualize the functional enrichment of MPC1 and signaling pathways related to MPC1. The correlation analysis was carried out to examine the relationship between MPC1 and Ferroptosis gene in TIMER 2.0, ncFO, GEPIA Database and Kaplan-Meier Plotter.
Results: We demonstrated that the expression levels of MPC1 in cervical cancer tissues were lower than those in normal cervical tissues. Kaplan-Meier survival curves showed shorter overall survival in cervical cancer patients with low levels of MPC1 expression. The expression of MPC1 was related to the infiltrating levels of tumor-infiltrating immune cells in cervical cancer. Moreover, MPC1 expression was associated with the iron-mediated cell death pathway, and several important ferroptosis genes were upregulated in cervical cancer cells. Furthermore, after knocking down MPC1 in HeLa cells, the expression of these genes decreased.
Conclusion: These findings indicate that MPC1 functions as a prognostic indicator and plays a role in the regulation of the ferroptosis pathway in cervical cancer.
{"title":"Exploring MPC1 as a potential ferroptosis-linked biomarker in the cervical cancer tumor microenvironment: a comprehensive analysis.","authors":"Miao Li, Tianhan Xu, Rui Yang, Xiaoyun Wang, Jiawen Zhang, Sufang Wu","doi":"10.1186/s12885-024-12622-x","DOIUrl":"10.1186/s12885-024-12622-x","url":null,"abstract":"<p><strong>Background: </strong>The increasing problems of drug and radiotherapy resistance in cervical cancer underscores the need for novel methods for its management. Reports indicate that the expression of MPC1 may be associated with the tumor microenvironment and the occurrence of ferroptosis in cervical cancer. The objective of this study was to visually illustrate the prognostic significance and immunological characterization of MPC1 in cervical cancer.</p><p><strong>Methods: </strong>The expression profile and prognostic significance of MPC1 were analyzed using various databases, including UALCAN, TIMER2, GEPIA2, and Kaplan-Meier Plotter. TISIDB, TIMER2, and immunohistochemical analysis were used to investigate the correlation between MPC1 expression and immune infiltration. GO enrichment analysis, KEGG analysis, Reactome analysis, ConsensusPathDB, and GeneMANIA were used to visualize the functional enrichment of MPC1 and signaling pathways related to MPC1. The correlation analysis was carried out to examine the relationship between MPC1 and Ferroptosis gene in TIMER 2.0, ncFO, GEPIA Database and Kaplan-Meier Plotter.</p><p><strong>Results: </strong>We demonstrated that the expression levels of MPC1 in cervical cancer tissues were lower than those in normal cervical tissues. Kaplan-Meier survival curves showed shorter overall survival in cervical cancer patients with low levels of MPC1 expression. The expression of MPC1 was related to the infiltrating levels of tumor-infiltrating immune cells in cervical cancer. Moreover, MPC1 expression was associated with the iron-mediated cell death pathway, and several important ferroptosis genes were upregulated in cervical cancer cells. Furthermore, after knocking down MPC1 in HeLa cells, the expression of these genes decreased.</p><p><strong>Conclusion: </strong>These findings indicate that MPC1 functions as a prognostic indicator and plays a role in the regulation of the ferroptosis pathway in cervical cancer.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Chronic inflammation is associated with the etiology of various cancers. However, there is a lack of systematic research in urologic cancers. This study aims to use a two-sample Mendelian randomization (MR) approach to evaluate the role of circulating cytokines in the development of urologic cancers.
Methods: We obtained the summary-level data for bladder cancer (373,295 cases and 372,016 controls), prostate cancer (462,933 cases and 459,664 controls), and kidney cancer (463,010 cases and 461,896 controls) from the UK Biobank. Genetic variations linked to 41 circulating cytokines were used as instrumental variables (IVs) in meta-analyses of genome-wide association studies (GWASs) involving 8,293 individuals from Finland. We primarily used the inverse-variance weighted (IVW) method to assess the potential associations between the 41 cytokines and the risk of 3 common urologic cancers. Weighted-median method, weighted mode and simple-median method were used to assess the sensitivity. Heterogeneity and pleiotropic outlier were evaluated by Cochran's Q test and MR-Egger regression. Genetic correlation, colocalization analysis and multivariable MR analysis were used to further validate the potential pleiotropy.
Results: After the Bonferroni correction, there was an observed association between elevated genetically predicted levels of CCL27 and a heightened risk for bladder cancer. Conversely, IL-12p70 levels were found to have a protective association against the risk of bladder cancer. Sensitivity analyses utilizing various IV sets and MR approach remained robust. Furthermore, we found potential associations of 7 cytokines with urologic cancers (4.07 × 10-4 ≤ P < 0.05).
Conclusion: Our study supported causal associations between CCL27, IL-12p70 and bladder cancer risk and potential associations of 7 cytokines with the risk of urologic cancers, helping us to further understand the pathogenesis of urologic cancers and providing clues for improving diagnostic accuracy and therapies.
{"title":"Circulating levels of cytokines and risk of urologic cancers: a two-sample Mendelian randomization study.","authors":"Jinbo Song, Xiaoke Sun, Ting Wang, Chao Li, Leihong Yuan","doi":"10.1186/s12885-024-13016-9","DOIUrl":"10.1186/s12885-024-13016-9","url":null,"abstract":"<p><strong>Background: </strong>Chronic inflammation is associated with the etiology of various cancers. However, there is a lack of systematic research in urologic cancers. This study aims to use a two-sample Mendelian randomization (MR) approach to evaluate the role of circulating cytokines in the development of urologic cancers.</p><p><strong>Methods: </strong>We obtained the summary-level data for bladder cancer (373,295 cases and 372,016 controls), prostate cancer (462,933 cases and 459,664 controls), and kidney cancer (463,010 cases and 461,896 controls) from the UK Biobank. Genetic variations linked to 41 circulating cytokines were used as instrumental variables (IVs) in meta-analyses of genome-wide association studies (GWASs) involving 8,293 individuals from Finland. We primarily used the inverse-variance weighted (IVW) method to assess the potential associations between the 41 cytokines and the risk of 3 common urologic cancers. Weighted-median method, weighted mode and simple-median method were used to assess the sensitivity. Heterogeneity and pleiotropic outlier were evaluated by Cochran's Q test and MR-Egger regression. Genetic correlation, colocalization analysis and multivariable MR analysis were used to further validate the potential pleiotropy.</p><p><strong>Results: </strong>After the Bonferroni correction, there was an observed association between elevated genetically predicted levels of CCL27 and a heightened risk for bladder cancer. Conversely, IL-12p70 levels were found to have a protective association against the risk of bladder cancer. Sensitivity analyses utilizing various IV sets and MR approach remained robust. Furthermore, we found potential associations of 7 cytokines with urologic cancers (4.07 × 10<sup>-4</sup> ≤ P < 0.05).</p><p><strong>Conclusion: </strong>Our study supported causal associations between CCL27, IL-12p70 and bladder cancer risk and potential associations of 7 cytokines with the risk of urologic cancers, helping us to further understand the pathogenesis of urologic cancers and providing clues for improving diagnostic accuracy and therapies.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}