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TP53 mutation status and consensus molecular subtypes of colorectal cancer in patients from Rwanda. 卢旺达结直肠癌患者的 TP53 基因突变状态和分子亚型共识。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2024-10-11 DOI: 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.

背景:TP53 抑癌基因的突变是结直肠癌(CRC)发病的公认驱动因素。然而,目前尚缺乏有关卢旺达 CRC 患者中 TP53 变异的发生率及其与共识分子亚型(CMS)分类的关系的数据。本研究通过调查卢旺达 CRC 队列中与 CMS 分类相关的 TP53 突变状态,填补了这一知识空白:方法:从卢旺达基加利大学教学医院的 51 名 CRC 患者身上获得了福尔马林固定石蜡包埋(FFPE)组织块。采用桑格测序法对 TP53 基因的第 4 至 11 号外显子及其侧翼的内含子-外显子边界进行了测序,以确定潜在的变异。采用最近建立的基于免疫组化的分类器来确定每个肿瘤的 CMS:癌症组织 DNA 的测序分析显示,卢旺达 51 名患者中有 23 人(45.1%)存在 TP53 致病变异。这些变异主要是错义类型(18/23,78.3%)。最常见的变异是 c.455dup (p.P153Afs*28)、c.524G > A (p.R175H) 和 c.733G > A (p.G245S),每个变异都在三个肿瘤中发现。对 23 个突变(其中 20 个为单碱基置换)的三核苷酸序列上下文分析表明,在单碱基置换(SBS)中,[C > N]模式占主导地位(18/20;90.0%),C[C > T]G 是最常见的突变(5/18,27.8%)。此外,嘧啶碱基(C 和 T)优先出现在突变胞嘧啶的 5' 侧翼位置(13/18;72.2%)。对 CMS 亚型的分析显示了以下分布情况:CMS1(微卫星不稳定性-免疫)(6/51,11.8%)、CMS2(典型)(28/51,54.9%)、CMS3(代谢)(9/51,17.6%)和CMS4(间质)(8/51,15.7%)。有趣的是,大多数 TP53 变体出现在 CMS2 亚组(14/23;60.1%):我们的研究结果表明,卢旺达的 CRC 患者中 TP53 变异的频率很高。结论:我们的研究结果表明,卢旺达的 CRC 患者中 TP53 变异的频率很高,重要的是,这些变异富集在 CMS2 亚型中。这项研究是对卢旺达 CRC 患者分子改变的第二次调查,也是对 TP53 变异和 CMS 分类的首次探索,为了解这一研究不足人群的 CRC 分子状况提供了有价值的见解。
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引用次数: 0
Construction and validation of a prognostic model of angiogenesis-related genes in multiple myeloma. 多发性骨髓瘤血管生成相关基因预后模型的构建与验证
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2024-10-11 DOI: 10.1186/s12885-024-13024-9
Rui Hu, Fengyu Chen, Xueting Yu, Zengzheng Li, Yujin Li, Shuai Feng, Jianqiong Liu, Huiyuan Li, Chengmin Shen, Xuezhong Gu, Zhixiang Lu

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。
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引用次数: 0
Effects of dietary habits and catheterization type on breast cancer-related lymphedema: a retrospective cohort study. 饮食习惯和导管类型对乳腺癌相关淋巴水肿的影响:一项回顾性队列研究。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2024-10-11 DOI: 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.

背景:了解导致乳腺癌相关淋巴水肿(BCRL)变异的因素是制定有针对性的干预措施以改善乳腺癌患者生活质量的重要第一步。目的:本研究旨在探讨饮食习惯和导尿方式等护理因素对乳腺癌相关淋巴水肿(BCRL)的影响:这项回顾性队列研究纳入了 1476 名在 2012 年 1 月 1 日至 2020 年 9 月 1 日期间接受手术的乳腺癌患者。淋巴水肿通过有效的自我报告问卷进行评估。所有研究数据均来自医疗记录和随访数据库。研究人员进行了多变量考克斯回归,以探讨饮食习惯和导管插入类型对BCRL的影响:结果显示,入院前进食高脂肪饮食的乳腺癌患者发生 BCRL 的风险增加(HR = 2.47;95% CI = 1.55-3.94;P 结论:入院前进食高脂肪饮食的乳腺癌患者发生 BCRL 的风险增加:入院前高脂肪饮食是淋巴水肿的独立风险因素。与 PICC 和留置针相比,TIVAP 对淋巴水肿没有保护作用。这一研究结果为制定有针对性的干预措施以减少淋巴水肿的发生率提供了新的思路。
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引用次数: 0
Pediatric pleuropulmonary blastoma: analysis of four cases. 小儿胸膜肺泡瘤:四例病例分析。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2024-10-11 DOI: 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}
引用次数: 0
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. 接受一线铂类和紫杉醇治疗的晚期和复发性宫颈癌患者使用或不使用免疫检查点抑制剂的疗效比较研究。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2024-10-11 DOI: 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}
引用次数: 0
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. 研究纤维蛋白原-白蛋白比值和肌肉疏松症的组合对预测接受根治手术的喉癌患者预后的意义。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2024-10-11 DOI: 10.1186/s12885-024-13039-2
Yizheng Zhang, Zhiyong Meng, Ming Lu, Shenjiong Ruan, Jiao Zhou, Mingchen Zhang, Yanjun Huang, Kehui Chen, Xinyuan Luo, Cheng-Ke Xie, Chaohui Zheng

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.

摘要本研究旨在探讨术前肌肉疏松症和炎症标志物对喉癌患者的影响,并建立一个新的评分系统来预测患者的预后:纳入2015年12月至2020年12月在福建医科大学附属第二医院接受喉癌(LC)喉切除术的患者。采用单变量和多变量分析确定独立预后因素。根据FAR和术前肌少症建立新的评分系统(SFAR),并进行统计分析:本研究共纳入 198 例符合入院标准的病例。多变量分析显示,术前肌肉疏松症、pTNM分期和FAR是喉癌的独立预后因素。根据这三个指标,我们建立了 SFAR 评分系统。多变量分析表明,SFAR 是喉癌的独立预测因素(p 结论:SFAR 是喉癌的独立预测因素:全身炎症和肌肉疏松症与喉癌术后预后密切相关。新的评分系统(SFAR)对改善喉癌手术患者的预后具有重要意义。
{"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}
引用次数: 0
Integrated bioinformatics analysis and experimental validation on malignant progression and immune cell infiltration of LTBP2 in gliomas. 胶质瘤中 LTBP2 恶性进展和免疫细胞浸润的综合生物信息学分析和实验验证。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2024-10-10 DOI: 10.1186/s12885-024-12976-2
Lun Gao, Rui Zhang, Wenbin Zhang, Yanfang Lan, Xiangpan Li, Qiang Cai, Junhui Liu

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.

背景:胶质瘤是侵袭性极强的脑肿瘤,也是最具破坏性的人类肿瘤。潜伏的 TGF 结合蛋白(LTBP)被发现参与了恶性生物过程,并可作为多种实体瘤的有效生物标记物。但LTBP家族在人类胶质瘤中的作用仍有待阐明:方法:从Gliovis下载了2407个胶质瘤样本的归一化基因表达和相应的临床数据。采用Western印迹(WB)和免疫组化(IHC)检测154个胶质瘤样本中LTBPs蛋白水平。免疫荧光(IF)和免疫组化(IHC)评估了胶质瘤组织中LTBP2表达与免疫浸润之间的相关性。CCK8和流式细胞分析被用来检测LTBP2对胶质瘤细胞的影响。利用离体胶质瘤小鼠模型评估其体内效应:结果:在XENA-TCGA_GTEx、Gill和Gravendeel数据集中,与非肿瘤脑组织相比,胶质瘤样本中LTBP2 mRNA水平显著升高(均为P):LTBP2可作为预后标志物,LTBP2的高表达与大量TAMs浸润和化疗反应较差有关。
{"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}
引用次数: 0
Newcastle disease virus enhances the antitumor efficacy of Doxorubicin in a cervical cancer mouse model. 在宫颈癌小鼠模型中,新城疫病毒可增强多柔比星的抗肿瘤疗效。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2024-10-10 DOI: 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.

背景和目的:宫颈癌(CC)是女性常见癌症,通常采用多柔比星(Doxo)治疗。研究人员正在探索使用溶瘤病毒(OV)疗法来提高药物疗效和增强免疫系统的抗肿瘤能力。因此,我们的研究旨在评估新城疫病毒(NDV)在CC小鼠模型中提高Doxo抗肿瘤疗效的治疗潜力:给 6 至 8 周龄的 C57BL/6 小鼠(雌性)注射 TC1 细胞(n = 40)以诱导肿瘤生长。肿瘤发生后,小鼠分成四个治疗组。通过 NDV、Doxo 和两者的组合进行治疗,三组治疗两次,干预一周,对照组用 PBS 治疗。最后一次治疗后,其中一半小鼠因免疫反应评估而被安乐死,另一半小鼠则接受随访,直到它们在一定时间内自然死亡:结果:与对照组相比,接受联合治疗的小鼠的存活率明显提高,肿瘤进展速度明显减慢。这种联合疗法大大提高了宫颈肿瘤小鼠脾细胞培养物中一氧化氮(NO)和乳酸脱氢酶(LDH)的水平。此外,与只用 NDV 或 Doxo 治疗相比,联合疗法显著提高了 TNF-α、IL-12 和 IFN-γ的分泌,同时减少了脾细胞内 TGF-β 和 IL-4 的释放:根据本研究的结果,在小鼠 CC 模型中使用 NDV 似乎可以提高 Doxo 的疗效,这表明 NDV 可以作为化疗的辅助疗法。
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引用次数: 0
Exploring MPC1 as a potential ferroptosis-linked biomarker in the cervical cancer tumor microenvironment: a comprehensive analysis. 探索宫颈癌肿瘤微环境中潜在的铁突变相关生物标记物 MPC1:一项综合分析。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2024-10-10 DOI: 10.1186/s12885-024-12622-x
Miao Li, Tianhan Xu, Rui Yang, Xiaoyun Wang, Jiawen Zhang, Sufang Wu

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.

背景:宫颈癌耐药和耐放疗的问题日益严重,这凸显了对新型治疗方法的需求。有报告显示,MPC1 的表达可能与宫颈癌的肿瘤微环境和铁变态反应的发生有关。本研究旨在直观地说明 MPC1 在宫颈癌中的预后意义和免疫学特征:方法:利用 UALCAN、TIMER2、GEPIA2 和 Kaplan-Meier Plotter 等多个数据库分析了 MPC1 的表达谱和预后意义。TISIDB、TIMER2和免疫组化分析用于研究MPC1表达与免疫浸润之间的相关性。GO富集分析、KEGG分析、Reactome分析、ConsensusPathDB和GeneMANIA用于观察MPC1及与MPC1相关的信号通路的功能富集。在TIMER 2.0、ncFO、GEPIA数据库和Kaplan-Meier Plotter中进行了相关性分析,以研究MPC1与铁突变基因之间的关系:结果:我们发现宫颈癌组织中 MPC1 的表达水平低于正常宫颈组织。Kaplan-Meier生存曲线显示,MPC1表达水平低的宫颈癌患者总生存期较短。MPC1的表达与宫颈癌中肿瘤浸润免疫细胞的浸润水平有关。此外,MPC1的表达与铁介导的细胞死亡途径有关,宫颈癌细胞中几个重要的铁变态反应基因被上调。此外,在敲除 HeLa 细胞中的 MPC1 后,这些基因的表达量减少:这些研究结果表明,MPC1 可作为预后指标,并在宫颈癌的铁氧化途径调控中发挥作用。
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引用次数: 0
Circulating levels of cytokines and risk of urologic cancers: a two-sample Mendelian randomization study. 细胞因子循环水平与泌尿系统癌症风险:一项双样本孟德尔随机研究。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2024-10-10 DOI: 10.1186/s12885-024-13016-9
Jinbo Song, Xiaoke Sun, Ting Wang, Chao Li, Leihong Yuan

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.

背景:慢性炎症与各种癌症的病因有关。然而,目前还缺乏对泌尿系统癌症的系统研究。本研究旨在使用双样本孟德尔随机化(MR)方法评估循环细胞因子在泌尿系统癌症发病中的作用:我们从英国生物库中获得了膀胱癌(373,295 例病例和 372,016 例对照)、前列腺癌(462,933 例病例和 459,664 例对照)和肾癌(463,010 例病例和 461,896 例对照)的汇总数据。在对涉及 8293 名芬兰人的全基因组关联研究(GWAS)进行的荟萃分析中,与 41 种循环细胞因子相关的基因变异被用作工具变量(IV)。我们主要采用逆方差加权法(IVW)来评估这 41 种细胞因子与 3 种常见泌尿系统癌症风险之间的潜在关联。加权中值法、加权模式和简单中值法被用来评估敏感性。通过 Cochran's Q 检验和 MR-Egger 回归评估了异质性和多向异常值。遗传相关性、共定位分析和多变量磁共振分析用于进一步验证潜在的多向性:结果:经 Bonferroni 校正后发现,基因预测的 CCL27 水平升高与膀胱癌风险升高之间存在关联。相反,IL-12p70水平对膀胱癌风险具有保护作用。利用各种IV组和MR方法进行的敏感性分析仍然很可靠。此外,我们还发现了 7 种细胞因子与泌尿系统癌症的潜在关联(4.07 × 10-4 ≤ P 结论:我们的研究支持细胞因子与膀胱癌之间的因果关系:我们的研究支持 CCL27、IL-12p70 与膀胱癌风险之间的因果关系,以及 7 种细胞因子与泌尿系统癌症风险之间的潜在关系,这有助于我们进一步了解泌尿系统癌症的发病机制,并为提高诊断准确性和改进治疗方法提供线索。
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引用次数: 0
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