Liver cancer is the second leading cause of tumor-related death worldwide, and a serious threat to lives and health. Circulating tumor cells (CTCs) facilitate the progression of various cancers, including liver cancer. The relationship between CTC/circulating tumor microemboli-related genes (CRGs) and the prognosis of liver cancer is unclear. The aim of the present study was to identify CTC/circulating tumour microemboli-related genes (CRGs) in hepatocellular carcinoma and to investigate their clinical significance. Transcriptomic data from The Cancer Genome Atlas (International Cancer Genome Consortium (ICGC) and GSE117623 databases were combined, and differentially expressed CRGs were identified. These were subsequently analyzed via least absolute shrinkage and selection operator and multivariate Cox analyses, and a five-gene risk signature was constructed. The signature was validated in the ICGC and GSE14520 dataset with survival analysis and receiver operating characteristic curve analysis. Immunocyte infiltration, tumor mutation burden (TMB), tumor immune dysfunction and exclusion (TIDE), and the somatic mutation rate were also compared between high- and low-risk groups, based on the median predictive index, to further evaluate the immunotherapeutic value of the model. Molecular subtypes of liver cancer were characterized by the non-negative matrix factorization method and potential therapeutic compounds were evaluated for different subtypes. Nomograms were utilized to predict the prognosis of patients, and the signature was compared with previous literature models. Additionally, the biological function of one of the CRGs, tumor protein p53 inducible protein 3 (TP53I3), in liver cancer was further explored through in vitro experiments. Analysis of the prognostic characteristics of the five CRGs led to the identification of two liver cancer subtypes. Patients in the low-risk group had a longer survival compared with those in the high-risk group, and patients in the latter group were associated with a higher TMB, immunocyte infiltration and somatic mutation rate, and lower TIDE scores. The prognostic profile was validated in the ICGC and GSE14520 datasets and exhibited a good predictive performance. In vitro analysis showed that the knockdown of TP53I3 suppressed liver cancer cell proliferation. In summary, CRGs were used to develop a new prognostic signature to predict the prognosis of patients with liver cancer. This signature may be used to assess the prognosis of patients and may provide new insights for clinical management strategies. In addition, TP53I3 is potentially a therapeutic target for liver cancer.
{"title":"Prognostic prediction signature and molecular subtype for liver cancer: A CTC/CTM‑related gene prediction model and independent external validation.","authors":"Ling Xu,Qiansheng Wu,Kai Zhao,Xiangyu Li,Wei Yao","doi":"10.3892/ol.2024.14664","DOIUrl":"https://doi.org/10.3892/ol.2024.14664","url":null,"abstract":"Liver cancer is the second leading cause of tumor-related death worldwide, and a serious threat to lives and health. Circulating tumor cells (CTCs) facilitate the progression of various cancers, including liver cancer. The relationship between CTC/circulating tumor microemboli-related genes (CRGs) and the prognosis of liver cancer is unclear. The aim of the present study was to identify CTC/circulating tumour microemboli-related genes (CRGs) in hepatocellular carcinoma and to investigate their clinical significance. Transcriptomic data from The Cancer Genome Atlas (International Cancer Genome Consortium (ICGC) and GSE117623 databases were combined, and differentially expressed CRGs were identified. These were subsequently analyzed via least absolute shrinkage and selection operator and multivariate Cox analyses, and a five-gene risk signature was constructed. The signature was validated in the ICGC and GSE14520 dataset with survival analysis and receiver operating characteristic curve analysis. Immunocyte infiltration, tumor mutation burden (TMB), tumor immune dysfunction and exclusion (TIDE), and the somatic mutation rate were also compared between high- and low-risk groups, based on the median predictive index, to further evaluate the immunotherapeutic value of the model. Molecular subtypes of liver cancer were characterized by the non-negative matrix factorization method and potential therapeutic compounds were evaluated for different subtypes. Nomograms were utilized to predict the prognosis of patients, and the signature was compared with previous literature models. Additionally, the biological function of one of the CRGs, tumor protein p53 inducible protein 3 (TP53I3), in liver cancer was further explored through in vitro experiments. Analysis of the prognostic characteristics of the five CRGs led to the identification of two liver cancer subtypes. Patients in the low-risk group had a longer survival compared with those in the high-risk group, and patients in the latter group were associated with a higher TMB, immunocyte infiltration and somatic mutation rate, and lower TIDE scores. The prognostic profile was validated in the ICGC and GSE14520 datasets and exhibited a good predictive performance. In vitro analysis showed that the knockdown of TP53I3 suppressed liver cancer cell proliferation. In summary, CRGs were used to develop a new prognostic signature to predict the prognosis of patients with liver cancer. This signature may be used to assess the prognosis of patients and may provide new insights for clinical management strategies. In addition, TP53I3 is potentially a therapeutic target for liver cancer.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"34 1","pages":"531"},"PeriodicalIF":2.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tabata Carolina Faria Nascimento de Assis,Liane Rapatoni,Flavio Nogueira Segato,Barbhara Thais Maciel Pontes,Valdair Francisco Muglia,Miguel Moyses Neto,Elen Almeida Romao
Collecting duct carcinoma (CDC) is a rare disease associated with a high mortality rate. The present study describes the case of a recipient of a kidney transplant with metastatic allograft CDC whose treatment was successful. The patient underwent nephrectomy, and chemotherapy with gemcitabine and cisplatin, while undergoing haemodialysis treatment and remained in remission after 6 years of follow-up. There is a lack of information about the treatment and clinical management of CDC; however, the combination of gemcitabine and cisplatin remains as first-line therapy. The challenge of this case was integrating chemotherapy sessions with dialysis therapy to maintain the effectiveness, tolerability and safety of the oncological treatment. In the present case report, the success of chemotherapy with gemcitabine and cisplatin was demonstrated in a metastatic renal allograft CDC in a patient with end-stage renal disease, with few side effects and no recurrence of the disease 6 years after the end of treatment.
{"title":"Effective treatment of collecting duct carcinoma in a recipient of a kidney transplant: A case report.","authors":"Tabata Carolina Faria Nascimento de Assis,Liane Rapatoni,Flavio Nogueira Segato,Barbhara Thais Maciel Pontes,Valdair Francisco Muglia,Miguel Moyses Neto,Elen Almeida Romao","doi":"10.3892/ol.2024.14661","DOIUrl":"https://doi.org/10.3892/ol.2024.14661","url":null,"abstract":"Collecting duct carcinoma (CDC) is a rare disease associated with a high mortality rate. The present study describes the case of a recipient of a kidney transplant with metastatic allograft CDC whose treatment was successful. The patient underwent nephrectomy, and chemotherapy with gemcitabine and cisplatin, while undergoing haemodialysis treatment and remained in remission after 6 years of follow-up. There is a lack of information about the treatment and clinical management of CDC; however, the combination of gemcitabine and cisplatin remains as first-line therapy. The challenge of this case was integrating chemotherapy sessions with dialysis therapy to maintain the effectiveness, tolerability and safety of the oncological treatment. In the present case report, the success of chemotherapy with gemcitabine and cisplatin was demonstrated in a metastatic renal allograft CDC in a patient with end-stage renal disease, with few side effects and no recurrence of the disease 6 years after the end of treatment.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"55 1","pages":"528"},"PeriodicalIF":2.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cisplatin resistance in ovarian cancer cells is mainly apoptosis resistant. Although other types of programmed cell death are highly involved in chemoresistance, which type can overcome cisplatin resistance remains unclear. The present study observed that cisplatin-sensitive SKOV3 cells and cisplatin-resistant SKOV3/DDP cells had different levels of sensitivity to sulfasalazine (SAS). The present study aimed to investigate the effect of SAS on necroptosis under the same inhibition rate in these two types of cells. Necroptosis inhibitor Necrostatin-1 (Nec-1) attenuated SAS-induced SKOV3/DDP cytotoxicity. SAS decreased SKOV3/DDP cells survival rate, accompanied by decreased cell adhesion and spreading. SAS treatment activated necrosome formation in SKOV3/DDP cells, suggesting the possibility of necroptosis. p62/sequestosome-1 (SQSTM1) protein expression levels were also increased over the same time period. The transfection of small interfering (si)-p62 could decrease the ratios of phosphorylated (p)-receptor-interacting serine/threonine kinase 1 (RIP1)/RIP1, p-receptor-interacting serine/threonine kinase 3 (RIP3)/RIP3 and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in SKOV3/DDP cells. Under the si-p62 condition, there was no increase in the rate of cell survival in Nec-1 and SAS combination group compared with SAS. The zinc finger domain deletion of p62/SQSTM1 effectively decreased the expression levels of necroptosis-related p-proteins. Collectively, certain drugs were able to induce necroptosis in SKOV3/DDP, while p62/RIP1/RIP3/MLKL was associated with the induction of necroptosis and with increasing the sensitivity of cisplatin-resistant ovarian cancer cells, which provided evidence for potential as a therapeutic target for overcoming resistance.
卵巢癌细胞的顺铂耐药性主要是凋亡耐药性。虽然其他类型的程序性细胞死亡与化疗耐药性有很大关系，但哪种类型的细胞死亡能克服顺铂耐药性仍不清楚。本研究观察到顺铂敏感的SKOV3细胞和顺铂耐药的SKOV3/DDP细胞对柳氮磺胺吡啶（SAS）的敏感性不同。本研究旨在探讨在相同抑制率下，SAS 对这两类细胞坏死突变的影响。坏死抑制剂Necrostatin-1（Nec-1）减轻了SAS诱导的SKOV3/DDP细胞毒性。SAS 降低了 SKOV3/DDP 细胞的存活率，同时降低了细胞的粘附性和扩散性。SAS 处理激活了 SKOV3/DDP 细胞中坏死体的形成，表明了坏死凋亡的可能性。转染小干扰（si）-p62可降低SKOV3/DDP细胞中磷酸化（p）-受体相互作用丝氨酸/苏氨酸激酶1（RIP1）/RIP1、p-受体相互作用丝氨酸/苏氨酸激酶3（RIP3）/RIP3和p-混合系激酶结构域样蛋白（MLKL）/MLKL蛋白的比例。在 si-p62 条件下，与 SAS 相比，Nec-1 和 SAS 组合组的细胞存活率没有增加。p62/SQSTM1 锌指结构域缺失能有效降低坏死相关 p 蛋白的表达水平。总之，某些药物能够诱导SKOV3/DDP的坏死，而p62/RIP1/RIP3/MLKL与坏死的诱导和顺铂耐药卵巢癌细胞敏感性的增加有关，这为作为克服耐药性的治疗靶点提供了证据。
{"title":"Zinc finger domain of p62/SQSTM1 is involved in the necroptosis of human cisplatin‑resistant ovarian cancer cells treated with sulfasalazine.","authors":"Nannan Liu,Shanshan Liu,Xueshuang Zhang,Wenzhu Tian,Heqiang Jia,Xin Ye,Xiaoyu Yan,Chunyan Yu,Huimei Yu","doi":"10.3892/ol.2024.14662","DOIUrl":"https://doi.org/10.3892/ol.2024.14662","url":null,"abstract":"Cisplatin resistance in ovarian cancer cells is mainly apoptosis resistant. Although other types of programmed cell death are highly involved in chemoresistance, which type can overcome cisplatin resistance remains unclear. The present study observed that cisplatin-sensitive SKOV3 cells and cisplatin-resistant SKOV3/DDP cells had different levels of sensitivity to sulfasalazine (SAS). The present study aimed to investigate the effect of SAS on necroptosis under the same inhibition rate in these two types of cells. Necroptosis inhibitor Necrostatin-1 (Nec-1) attenuated SAS-induced SKOV3/DDP cytotoxicity. SAS decreased SKOV3/DDP cells survival rate, accompanied by decreased cell adhesion and spreading. SAS treatment activated necrosome formation in SKOV3/DDP cells, suggesting the possibility of necroptosis. p62/sequestosome-1 (SQSTM1) protein expression levels were also increased over the same time period. The transfection of small interfering (si)-p62 could decrease the ratios of phosphorylated (p)-receptor-interacting serine/threonine kinase 1 (RIP1)/RIP1, p-receptor-interacting serine/threonine kinase 3 (RIP3)/RIP3 and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in SKOV3/DDP cells. Under the si-p62 condition, there was no increase in the rate of cell survival in Nec-1 and SAS combination group compared with SAS. The zinc finger domain deletion of p62/SQSTM1 effectively decreased the expression levels of necroptosis-related p-proteins. Collectively, certain drugs were able to induce necroptosis in SKOV3/DDP, while p62/RIP1/RIP3/MLKL was associated with the induction of necroptosis and with increasing the sensitivity of cisplatin-resistant ovarian cancer cells, which provided evidence for potential as a therapeutic target for overcoming resistance.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"17 1","pages":"529"},"PeriodicalIF":2.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Malignant melanoma meningeal metastasis (MMMM) is a rare clinical condition with a poor prognosis. The observation of hemorrhagic cerebrospinal fluid (CSF) in this type of disease is relatively uncommon and may indicate disease progression. The present study reports the case of a 51-year-old male with malignant melanoma who presented with a headache. Imaging studies did not identify abnormalities; however, an analysis of the CSF revealed hemorrhagic changes. The results of cytological examination of the CSF showed melanoma cells, leading to the final diagnosis of MMMM. This case emphasizes the importance of monitoring neurological symptoms and conducting comprehensive CSF cytological examination in patients with melanoma, creating disease awareness in clinicians.
{"title":"Malignant melanoma meningeal metastasis with concurrent hemorrhagic cerebrospinal fluid: A case report.","authors":"Qing Ma,Bo Song,Kun Cao,Xiaoyun She,Wei Chen,Weijun Wang,Huiying Huang","doi":"10.3892/ol.2024.14665","DOIUrl":"https://doi.org/10.3892/ol.2024.14665","url":null,"abstract":"Malignant melanoma meningeal metastasis (MMMM) is a rare clinical condition with a poor prognosis. The observation of hemorrhagic cerebrospinal fluid (CSF) in this type of disease is relatively uncommon and may indicate disease progression. The present study reports the case of a 51-year-old male with malignant melanoma who presented with a headache. Imaging studies did not identify abnormalities; however, an analysis of the CSF revealed hemorrhagic changes. The results of cytological examination of the CSF showed melanoma cells, leading to the final diagnosis of MMMM. This case emphasizes the importance of monitoring neurological symptoms and conducting comprehensive CSF cytological examination in patients with melanoma, creating disease awareness in clinicians.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"21 1","pages":"532"},"PeriodicalIF":2.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Head and neck cancer (HNC) is the sixth most common type of cancer worldwide, and head and neck squamous cell carcinoma (HNSCC) accounts for 90% of HNC cases. Furthermore, HNSCC accounts for 400,000 cancer-associated deaths worldwide each year. However, at present there is an absence of a versatile biomarker that can be used for diagnosis, prognosis evaluation and as a therapeutic target for HNSCC. In the present study, bioinformatics analysis was used to assess the relationship between hub genes and the clinical features of patients with HNSCC. The findings from the bioinformatics analysis were then verified using clinical samples and in vitro experiments. A total of 51 overlapping genes were identified from the intersection of differentially expressed genes and co-expressed genes. The top 10 hub genes were obtained from a protein-protein interaction network of overlapping genes. Among the hub genes, only secretoglobin family 1A member 1 (SCGB1A1) was significantly associated with both overall and disease-free survival. Specifically, upregulated SCGB1A1 expression levels were associated with prolonged overall and disease-free survival. Moreover, the SCGB1A1 expression levels were negatively correlated with drug sensitivity. Notably, it was demonstrated that SCGB1A1 was involved in tumor immunoreaction by affecting the infiltration of cells and checkpoint regulation of immune cells. Additionally, it was shown that SCGB1A1 regulated multiple key cancer-related signaling pathways, including extracellular matrix receptor interaction, transforming growth factor-β and tumor metabolism signaling pathways. Based on the results of the present study, SCGB1A1 may serve as a novel biomarker for predicting the diagnosis, prognosis and therapeutic effectiveness of certain drugs in patients with HNSCC. Moreover, SCGB1A1 may serve as a potential therapeutic target for the management of HNSCC.
{"title":"SCGB1A1 as a novel biomarker and promising therapeutic target for the management of HNSCC.","authors":"Jing Wang,Qianqian Xu,Jiangbo Yu,Aotian Xu,Lizheng Yu,Zhenggang Chen,Yang Cao,Rongtao Yuan,Zhongjie Yu","doi":"10.3892/ol.2024.14660","DOIUrl":"https://doi.org/10.3892/ol.2024.14660","url":null,"abstract":"Head and neck cancer (HNC) is the sixth most common type of cancer worldwide, and head and neck squamous cell carcinoma (HNSCC) accounts for 90% of HNC cases. Furthermore, HNSCC accounts for 400,000 cancer-associated deaths worldwide each year. However, at present there is an absence of a versatile biomarker that can be used for diagnosis, prognosis evaluation and as a therapeutic target for HNSCC. In the present study, bioinformatics analysis was used to assess the relationship between hub genes and the clinical features of patients with HNSCC. The findings from the bioinformatics analysis were then verified using clinical samples and in vitro experiments. A total of 51 overlapping genes were identified from the intersection of differentially expressed genes and co-expressed genes. The top 10 hub genes were obtained from a protein-protein interaction network of overlapping genes. Among the hub genes, only secretoglobin family 1A member 1 (SCGB1A1) was significantly associated with both overall and disease-free survival. Specifically, upregulated SCGB1A1 expression levels were associated with prolonged overall and disease-free survival. Moreover, the SCGB1A1 expression levels were negatively correlated with drug sensitivity. Notably, it was demonstrated that SCGB1A1 was involved in tumor immunoreaction by affecting the infiltration of cells and checkpoint regulation of immune cells. Additionally, it was shown that SCGB1A1 regulated multiple key cancer-related signaling pathways, including extracellular matrix receptor interaction, transforming growth factor-β and tumor metabolism signaling pathways. Based on the results of the present study, SCGB1A1 may serve as a novel biomarker for predicting the diagnosis, prognosis and therapeutic effectiveness of certain drugs in patients with HNSCC. Moreover, SCGB1A1 may serve as a potential therapeutic target for the management of HNSCC.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"76 1","pages":"527"},"PeriodicalIF":2.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ovarian serous carcinoma is a gynecological malignancy associated with a high mortality rate, which is commonly diagnosed in the first instance at a late stage and has a propensity to develop resistance to platinum-based chemotherapy. Identifying reliable biomarkers for platinum sensitivity is critical for improving patient outcomes. The present retrospective study included 64 patients with high-grade serous ovarian carcinoma (Federation of Gynecology and Obstetrics stages III or IV). Patients were classified as platinum-sensitive (no relapse within 6 months of the last platinum administration) or platinum-resistant (relapse within 6 months). Immunohistochemical analysis was performed to evaluate Fyn expression in tumor tissues, and Fyn knockdown experiments were performed using the OVSAHO ovarian cancer cell line to assess carboplatin sensitivity. Fyn expression was significantly higher in platinum-resistant patients compared with in platinum-sensitive patients (P<0.01). A weighted Fyn expression score was developed and a cutoff score of 6 was determined to predict platinum sensitivity with a specificity of 65.5% and a sensitivity of 62.9%. Patients with low Fyn expression (score ≤6) exhibited higher platinum sensitivity and longer overall survival (P<0.05). Multivariate analysis identified Fyn expression and postoperative residual tumor size as independent predictors of platinum sensitivity (P=0.033 and P=0.023, respectively). In vitro, Fyn knockdown significantly increased carboplatin sensitivity in ovarian cancer cells (P<0.05). Fyn, a member of the Src family of kinases, serves a crucial role in various cellular functions and has been implicated in chemotherapy resistance. The results demonstrated a notable association between Fyn expression and platinum sensitivity in ovarian serous carcinoma. The findings suggested that Fyn may serve as a predictive biomarker for response to platinum-based chemotherapy, offering the potential for more personalized treatment strategies. To the best of our knowledge, the present study is the first to establish an association between Fyn expression and platinum sensitivity in advanced ovarian serous carcinoma. Prospective studies with larger, multi-center cohorts and comprehensive biomarker analyses are recommended to validate and extend these results, ultimately improving therapeutic strategies and patient prognosis.
{"title":"Role of Fyn expression in predicting the sensitivity to platinum‑based chemotherapy in patients with ovarian serous carcinoma.","authors":"Eijiro Uchikura,Takeshi Fukuda,Tomoki Sengiku,Takuya Noda,Yuichiro Awazu,Takuma Wada,Reiko Tasaka,Makoto Yamauchi,Tomoyo Yasui,Toshiyuki Sumi","doi":"10.3892/ol.2024.14658","DOIUrl":"https://doi.org/10.3892/ol.2024.14658","url":null,"abstract":"Ovarian serous carcinoma is a gynecological malignancy associated with a high mortality rate, which is commonly diagnosed in the first instance at a late stage and has a propensity to develop resistance to platinum-based chemotherapy. Identifying reliable biomarkers for platinum sensitivity is critical for improving patient outcomes. The present retrospective study included 64 patients with high-grade serous ovarian carcinoma (Federation of Gynecology and Obstetrics stages III or IV). Patients were classified as platinum-sensitive (no relapse within 6 months of the last platinum administration) or platinum-resistant (relapse within 6 months). Immunohistochemical analysis was performed to evaluate Fyn expression in tumor tissues, and Fyn knockdown experiments were performed using the OVSAHO ovarian cancer cell line to assess carboplatin sensitivity. Fyn expression was significantly higher in platinum-resistant patients compared with in platinum-sensitive patients (P<0.01). A weighted Fyn expression score was developed and a cutoff score of 6 was determined to predict platinum sensitivity with a specificity of 65.5% and a sensitivity of 62.9%. Patients with low Fyn expression (score ≤6) exhibited higher platinum sensitivity and longer overall survival (P<0.05). Multivariate analysis identified Fyn expression and postoperative residual tumor size as independent predictors of platinum sensitivity (P=0.033 and P=0.023, respectively). In vitro, Fyn knockdown significantly increased carboplatin sensitivity in ovarian cancer cells (P<0.05). Fyn, a member of the Src family of kinases, serves a crucial role in various cellular functions and has been implicated in chemotherapy resistance. The results demonstrated a notable association between Fyn expression and platinum sensitivity in ovarian serous carcinoma. The findings suggested that Fyn may serve as a predictive biomarker for response to platinum-based chemotherapy, offering the potential for more personalized treatment strategies. To the best of our knowledge, the present study is the first to establish an association between Fyn expression and platinum sensitivity in advanced ovarian serous carcinoma. Prospective studies with larger, multi-center cohorts and comprehensive biomarker analyses are recommended to validate and extend these results, ultimately improving therapeutic strategies and patient prognosis.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"82 1","pages":"525"},"PeriodicalIF":2.9,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Breast cancer is the most prevalent neoplasm affecting women globally, of which a notable proportion of cases are triple-negative breast cancer (TNBC). However, there are limited curative treatment options for patients with TNBC, despite advancements in the field. Amino acids and amino acid transporters serve vital roles in the regulation of tumor metabolism. Notably, cystine and cysteine can interconvert via a redox reaction, with cysteine exerting control on cell survival and growth and exogenous cystine serving a crucial role in the proliferation of numerous types of cancers. Breast cancer has been reported to disrupt the cystine/cysteine metabolism pathway, as cystine and cysteine transporters affect the development and growth of tumors. The present review aims to provide a comprehensive overview of the metabolic pathways involving cystine and cysteine in normal and TNBC cells. Furthermore, the roles of cystine and cysteine transporters in TNBC progression and metastasis and their potential as therapeutic targets for treatment of TNBC are evaluated.
{"title":"Cystine/cysteine metabolism regulates the progression and response to treatment of triple‑negative breast cancer (Review).","authors":"Wanting Xiao,Chaoyang Xu","doi":"10.3892/ol.2024.14654","DOIUrl":"https://doi.org/10.3892/ol.2024.14654","url":null,"abstract":"Breast cancer is the most prevalent neoplasm affecting women globally, of which a notable proportion of cases are triple-negative breast cancer (TNBC). However, there are limited curative treatment options for patients with TNBC, despite advancements in the field. Amino acids and amino acid transporters serve vital roles in the regulation of tumor metabolism. Notably, cystine and cysteine can interconvert via a redox reaction, with cysteine exerting control on cell survival and growth and exogenous cystine serving a crucial role in the proliferation of numerous types of cancers. Breast cancer has been reported to disrupt the cystine/cysteine metabolism pathway, as cystine and cysteine transporters affect the development and growth of tumors. The present review aims to provide a comprehensive overview of the metabolic pathways involving cystine and cysteine in normal and TNBC cells. Furthermore, the roles of cystine and cysteine transporters in TNBC progression and metastasis and their potential as therapeutic targets for treatment of TNBC are evaluated.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"23 1","pages":"521"},"PeriodicalIF":2.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Endometriosis-associated adenocarcinoma of the rectum is rare and is usually misdiagnosed as colorectal carcinoma or other gynecological tumors. In the current report, the clinicopathological features of endometriosis-associated adenocarcinoma of the rectum in 2 patients were retrospectively analyzed and a literature review regarding this rare malignancy is presented. Case 1, a 49-year-old postmenopausal female patient, was admitted to Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology (Wuhan, China) due to a pelvic mass. Pelvic MRI revealed a 4.5×3.7-cm mass in the rectal wall, which severely adhered to the uterine wall. Microscopically, moderately differentiated glandular adenocarcinoma diffusely extended throughout all intestinal wall layers. Adenomyosis was found in the uterine body adherent to the rectum. Case 2, a 38-year-old reproductive female patient, presented with hematochezia. Histopathology of the resected tumor demonstrated benign endometriosis foci and atypical hyperplasia glands contiguous with endometrioid carcinoma invading the intestinal wall, and no other primary tumor sites were found, which satisfied the criteria for the diagnosis of malignant transformation of endometriosis of the rectum. Immunohistochemical (IHC) staining of both tumors revealed a Müllerian origin but not an intestinal origin. Furthermore, next-generation sequencing detected mutations of the BRCA1 (c.329dup), KRAS (c.35G>T), PIK3CA (c.3140A>G) and PTEN (c.750_751del) genes, and that microsatellite instability was high in case 1. In conclusion, endometriosis-associated adenocarcinoma of the rectum is a rare malignant tumor that should be distinguished from colorectal carcinoma for optimal treatment. Surgery and pathologic examination with IHC staining, even with molecular analysis, are essential for the final diagnosis. Primary cytoreductive surgery with resection of all macroscopic detectable lesions should be performed whenever possible. More prospective, multicenter, large-scale trials are required to examine the regimens and therapeutic value of adjuvant chemotherapy or radiology.
{"title":"Clinicopathological features of endometriosis‑associated adenocarcinoma of the rectum: A report of two cases.","authors":"Ke Zhao,Min Hu,Xiaowen Li,Runfeng Yang,Yi Huang","doi":"10.3892/ol.2024.14656","DOIUrl":"https://doi.org/10.3892/ol.2024.14656","url":null,"abstract":"Endometriosis-associated adenocarcinoma of the rectum is rare and is usually misdiagnosed as colorectal carcinoma or other gynecological tumors. In the current report, the clinicopathological features of endometriosis-associated adenocarcinoma of the rectum in 2 patients were retrospectively analyzed and a literature review regarding this rare malignancy is presented. Case 1, a 49-year-old postmenopausal female patient, was admitted to Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology (Wuhan, China) due to a pelvic mass. Pelvic MRI revealed a 4.5×3.7-cm mass in the rectal wall, which severely adhered to the uterine wall. Microscopically, moderately differentiated glandular adenocarcinoma diffusely extended throughout all intestinal wall layers. Adenomyosis was found in the uterine body adherent to the rectum. Case 2, a 38-year-old reproductive female patient, presented with hematochezia. Histopathology of the resected tumor demonstrated benign endometriosis foci and atypical hyperplasia glands contiguous with endometrioid carcinoma invading the intestinal wall, and no other primary tumor sites were found, which satisfied the criteria for the diagnosis of malignant transformation of endometriosis of the rectum. Immunohistochemical (IHC) staining of both tumors revealed a Müllerian origin but not an intestinal origin. Furthermore, next-generation sequencing detected mutations of the BRCA1 (c.329dup), KRAS (c.35G>T), PIK3CA (c.3140A>G) and PTEN (c.750_751del) genes, and that microsatellite instability was high in case 1. In conclusion, endometriosis-associated adenocarcinoma of the rectum is a rare malignant tumor that should be distinguished from colorectal carcinoma for optimal treatment. Surgery and pathologic examination with IHC staining, even with molecular analysis, are essential for the final diagnosis. Primary cytoreductive surgery with resection of all macroscopic detectable lesions should be performed whenever possible. More prospective, multicenter, large-scale trials are required to examine the regimens and therapeutic value of adjuvant chemotherapy or radiology.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"27 1","pages":"523"},"PeriodicalIF":2.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu Wang,Qinqin Sun,Zhijian Li,Fei Leng,Xuelian Han,Qiqi Su,Sheng Su
Uveal melanoma is the most common intraocular malignant tumor in adults. For patients presenting with cataracts and glaucoma, it is recommended to assess whether an intraocular lesion is present as the primary cause. The present study describes the case of a 52-year-old man with primary intraocular malignant melanoma. The patient experienced painless vision loss in the right eye for 1 year, with recent onset of eye swelling and pain in the week prior to seeking medical attention. A slit-lamp examination revealed a shallow anterior chamber in the right eye, a visibly opaque lens and a faint reflection of the tumor surface in the vitreous humor. In addition, the intraocular pressure of this eye was >60 mmHg. Magnetic resonance imaging revealed a large tumor behind the lens measuring 16×18×14 mm. Pathological examination confirmed the diagnosis of malignant melanoma. No BRCA-associated protein-1 somatic mutation was detected, whereas germline mutations of MutL protein homolog 1, RAD54 like, and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 were identified. Extensive systemic examination excluded the possibility that the tumors originated from another part of the body. The present case report highlights the crucial role of slit-lamp examination in the detection of ocular tumors. It is advocated that for patients presenting with cataracts, attention should be paid to the possibility of intraocular tumors. Meticulous slit-lamp microscopy may reveal a reflection of the surface of a malignant melanoma, preventing misdiagnosis.
{"title":"Malignant melanoma complicated with cataract and secondary glaucoma: A case report.","authors":"Yu Wang,Qinqin Sun,Zhijian Li,Fei Leng,Xuelian Han,Qiqi Su,Sheng Su","doi":"10.3892/ol.2024.14653","DOIUrl":"https://doi.org/10.3892/ol.2024.14653","url":null,"abstract":"Uveal melanoma is the most common intraocular malignant tumor in adults. For patients presenting with cataracts and glaucoma, it is recommended to assess whether an intraocular lesion is present as the primary cause. The present study describes the case of a 52-year-old man with primary intraocular malignant melanoma. The patient experienced painless vision loss in the right eye for 1 year, with recent onset of eye swelling and pain in the week prior to seeking medical attention. A slit-lamp examination revealed a shallow anterior chamber in the right eye, a visibly opaque lens and a faint reflection of the tumor surface in the vitreous humor. In addition, the intraocular pressure of this eye was >60 mmHg. Magnetic resonance imaging revealed a large tumor behind the lens measuring 16×18×14 mm. Pathological examination confirmed the diagnosis of malignant melanoma. No BRCA-associated protein-1 somatic mutation was detected, whereas germline mutations of MutL protein homolog 1, RAD54 like, and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 were identified. Extensive systemic examination excluded the possibility that the tumors originated from another part of the body. The present case report highlights the crucial role of slit-lamp examination in the detection of ocular tumors. It is advocated that for patients presenting with cataracts, attention should be paid to the possibility of intraocular tumors. Meticulous slit-lamp microscopy may reveal a reflection of the surface of a malignant melanoma, preventing misdiagnosis.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"49 1","pages":"520"},"PeriodicalIF":2.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jared E Limones-Gonzalez,Perla Aguilar Esquivel,Karla Vazquez-Santillan,Rosario Castro-Oropeza,Floria Lizarraga,Vilma Maldonado,Jorge Melendez-Zajgla,Patricia Piña-Sanchez,Gretel Mendoza-Almanza
Cancer is a multifactorial disease characterized by the loss of control in the expression of genes known as cancer driver genes. Cancer driver genes trigger uncontrolled cell replication, which leads to the development of malignant tumors. A cluster of signal transduction pathways that contain cancer driver genes involved in cellular processes, such as cell proliferation, differentiation, apoptosis and dysregulated organ growth, are associated with cancer initiation and progression. In the present study, three signal transduction pathways involved in cervical cancer (CC) development were analyzed: The Hippo pathway (FAT atypical cadherin, yes-associated protein 1, SMAD4 and TEA domain family member 2), the Notch pathway [cellular-MYC, cAMP response element-binding binding protein (CREBBP), E1A-associated cellular p300 transcriptional co-activator protein and F-Box and WD repeat domain containing 7] and the nuclear factor erythroid 2-related factor 2 (NRF2) pathway [NRF2, kelch-like ECH-associated protein 1 (KEAP1), AKT and PIK3-catalytic subunit α]. Tumor samples from patients diagnosed with various stages of CC, including cervical intraepithelial neoplasia (CIN) 1, CIN 2, CIN 3, in situ CC and invasive CC, were analyzed. The mRNA expression levels were analyzed using reverse transcription-quantitative PCR assays, whereas protein expression levels were assessed through immunohistochemical tissue microarrays. High mRNA expression levels of c-MYC and AKT and low expression levels of NRF2 and KEAP1 were associated with a decreased survival time of patients with CC. Additionally, increased expression levels of c-MYC were detected in the invasive CC stage. At the protein level, increased NRF2 expression levels were observed in all five stages of CC samples compared with those in the cancer-free control samples. AKT1 was found to be dysregulated in the CIN 1 and CIN 2 stages, PI3K in the in situ and invasive stages, and CREBBP in the CIN 3 and in situ stages. In summary, the present study demonstrated significant changes in proteins of the Notch and NRF2 pathways in CC. NRF2 was overexpressed in all cervical cancer stages (cervical intraepithelial neoplasia, in situ CC and invasive CC). The present study makes an important contribution to the possible biomarker proteins to be analyzed for the presence of premalignant and malignant lesions in the cervix.
{"title":"Changes in the molecular nodes of the Notch and NRF2 pathways in cervical cancer tissues from the precursor stages to invasive carcinoma.","authors":"Jared E Limones-Gonzalez,Perla Aguilar Esquivel,Karla Vazquez-Santillan,Rosario Castro-Oropeza,Floria Lizarraga,Vilma Maldonado,Jorge Melendez-Zajgla,Patricia Piña-Sanchez,Gretel Mendoza-Almanza","doi":"10.3892/ol.2024.14655","DOIUrl":"https://doi.org/10.3892/ol.2024.14655","url":null,"abstract":"Cancer is a multifactorial disease characterized by the loss of control in the expression of genes known as cancer driver genes. Cancer driver genes trigger uncontrolled cell replication, which leads to the development of malignant tumors. A cluster of signal transduction pathways that contain cancer driver genes involved in cellular processes, such as cell proliferation, differentiation, apoptosis and dysregulated organ growth, are associated with cancer initiation and progression. In the present study, three signal transduction pathways involved in cervical cancer (CC) development were analyzed: The Hippo pathway (FAT atypical cadherin, yes-associated protein 1, SMAD4 and TEA domain family member 2), the Notch pathway [cellular-MYC, cAMP response element-binding binding protein (CREBBP), E1A-associated cellular p300 transcriptional co-activator protein and F-Box and WD repeat domain containing 7] and the nuclear factor erythroid 2-related factor 2 (NRF2) pathway [NRF2, kelch-like ECH-associated protein 1 (KEAP1), AKT and PIK3-catalytic subunit α]. Tumor samples from patients diagnosed with various stages of CC, including cervical intraepithelial neoplasia (CIN) 1, CIN 2, CIN 3, in situ CC and invasive CC, were analyzed. The mRNA expression levels were analyzed using reverse transcription-quantitative PCR assays, whereas protein expression levels were assessed through immunohistochemical tissue microarrays. High mRNA expression levels of c-MYC and AKT and low expression levels of NRF2 and KEAP1 were associated with a decreased survival time of patients with CC. Additionally, increased expression levels of c-MYC were detected in the invasive CC stage. At the protein level, increased NRF2 expression levels were observed in all five stages of CC samples compared with those in the cancer-free control samples. AKT1 was found to be dysregulated in the CIN 1 and CIN 2 stages, PI3K in the in situ and invasive stages, and CREBBP in the CIN 3 and in situ stages. In summary, the present study demonstrated significant changes in proteins of the Notch and NRF2 pathways in CC. NRF2 was overexpressed in all cervical cancer stages (cervical intraepithelial neoplasia, in situ CC and invasive CC). The present study makes an important contribution to the possible biomarker proteins to be analyzed for the presence of premalignant and malignant lesions in the cervix.","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"38 1","pages":"522"},"PeriodicalIF":2.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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