L. Teng, Liuyuan Zhao, H. Shao, J. Dai, Hui-Ling Zou
Background: Studies have reported that blood transfusion may have an association with survival outcomes of cancer patients. This study was aimed at finding the effect of intra-operative blood transfusion on the prognosis of patients of hepatocellular carcinoma (HCC). Methods: This was a retrospective study. HCC patients who underwent tumor resection from January 2013 to November 2018 at Harbin Medical University Cancer Hospital were included. The survival time of patients receiving or not receiving blood transfusion during the operation were compared. Results: Of HCC patients, 21.1% (102/484) received intra-operative blood transfusion. After propensity score matching, 87 pairs of patients were included in the study. In the subset of patients with a tumor size of >4 cm, univariable analysis found that there were significant differences in recurrence-free survival (RFS; P=0.004) and overall survival (OS; P=0.028) between blood transfusion and non-blood transfusion groups. After multivariable Cox regression analysis, intra-operative blood transfusion was an independent risk factor for RFS (HR: 2.011, 95% CI: 1.146–3.529, P=0.015), but not for OS (HR: 1.862, 95% CI: 0.933–3.715, P=0.078) in the subset of patients with a tumor size of >4 cm. Conclusion: Intra-operative blood transfusion was associated with worse RFS in HCC patients with a tumor size of >4 cm.
{"title":"Negative Impact of Intra-Operative Blood Transfusion on Survival Outcomes of Hepatocellular Carcinoma Patients","authors":"L. Teng, Liuyuan Zhao, H. Shao, J. Dai, Hui-Ling Zou","doi":"10.2147/cmar.s448629","DOIUrl":"https://doi.org/10.2147/cmar.s448629","url":null,"abstract":"Background: Studies have reported that blood transfusion may have an association with survival outcomes of cancer patients. This study was aimed at finding the effect of intra-operative blood transfusion on the prognosis of patients of hepatocellular carcinoma (HCC). Methods: This was a retrospective study. HCC patients who underwent tumor resection from January 2013 to November 2018 at Harbin Medical University Cancer Hospital were included. The survival time of patients receiving or not receiving blood transfusion during the operation were compared. Results: Of HCC patients, 21.1% (102/484) received intra-operative blood transfusion. After propensity score matching, 87 pairs of patients were included in the study. In the subset of patients with a tumor size of >4 cm, univariable analysis found that there were significant differences in recurrence-free survival (RFS; P=0.004) and overall survival (OS; P=0.028) between blood transfusion and non-blood transfusion groups. After multivariable Cox regression analysis, intra-operative blood transfusion was an independent risk factor for RFS (HR: 2.011, 95% CI: 1.146–3.529, P=0.015), but not for OS (HR: 1.862, 95% CI: 0.933–3.715, P=0.078) in the subset of patients with a tumor size of >4 cm. Conclusion: Intra-operative blood transfusion was associated with worse RFS in HCC patients with a tumor size of >4 cm.","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140766253","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}
Purpose: Large animal models are still used in many studies because of their likeness to humans. It has not been documented that regular-sized conventional farm-breed pigs, generally bred for meat production, can be used to generate hepatocellular carcinoma (HCC) animal models. The goal of this study was to investigate how N-diethylnitrosamine (DENA) and phenobarbital (PB) together can generate HCC in ordinary farmed pigs. Materials and Methods: Conventional domestic swine (Sus scrofa domesticus) were used. DENA 15 mg/kg was intraperitoneally injected weekly for 12 weeks, while PB tablets (4 mg/kg) were also administered through food for 16 weeks. Blood testing and ultrasonography evaluation were performed to monitor the progress. Subsequently, computed tomography was conducted in cases with suspected nodules, followed by histopathological examination to confirm the diagnosis. Results: Ten swine (seven males, three females; age: 2 months; weight: 9– 15 kg) were included in the study and followed up for 25 months; nine were experimental, and one was control for ethical considerations. The maximum weight of animals during this study reached 162– 228 kg. The weight gain seen in the intervention swine was predominantly lower than that documented in the control. The laboratory analysis revealed no notable abnormalities in liver function markers but did demonstrate statistically significant changes in urea (p = 0.028) and creatinine (p = 0.003) levels. Ultrasonography and computed tomography showed multiple liver nodules with characteristics resembling HCC. Serial imaging screening and more extended observations revealed that all animals eventually developed tumors. Histopathological confirmation at 15– 22 weeks post-induction revealed that all intervened swine developed multiple nodules of well-differentiated HCC and some with hepatic angiosarcoma. Conclusion: This study successfully generated HCC in conventional domestic swine with a DENA and PB combination. This investigation required at least 15 months to develop tumors. This model will be beneficial for future investigations of HCC in large animals.
Keywords: carcinogenesis, large animal model, hepatocellular carcinoma, domestic swine, DENA induction
{"title":"Induction of Hepatocellular Carcinoma in Conventional Domestic Swine Using N-Diethylnitrosamine and Phenobarbital","authors":"Angela Giselvania, Vetnizah Juniantito, Heri Wibowo, Trifonia Pingkan Siregar, Soehartati Gondhowiardjo","doi":"10.2147/cmar.s439787","DOIUrl":"https://doi.org/10.2147/cmar.s439787","url":null,"abstract":"<strong>Purpose:</strong> Large animal models are still used in many studies because of their likeness to humans. It has not been documented that regular-sized conventional farm-breed pigs, generally bred for meat production, can be used to generate hepatocellular carcinoma (HCC) animal models. The goal of this study was to investigate how N-diethylnitrosamine (DENA) and phenobarbital (PB) together can generate HCC in ordinary farmed pigs.<br/><strong>Materials and Methods:</strong> Conventional domestic swine (<em>Sus scrofa domesticus</em>) were used. DENA 15 mg/kg was intraperitoneally injected weekly for 12 weeks, while PB tablets (4 mg/kg) were also administered through food for 16 weeks. Blood testing and ultrasonography evaluation were performed to monitor the progress. Subsequently, computed tomography was conducted in cases with suspected nodules, followed by histopathological examination to confirm the diagnosis.<br/><strong>Results:</strong> Ten swine (seven males, three females; age: 2 months; weight: 9– 15 kg) were included in the study and followed up for 25 months; nine were experimental, and one was control for ethical considerations. The maximum weight of animals during this study reached 162– 228 kg. The weight gain seen in the intervention swine was predominantly lower than that documented in the control. The laboratory analysis revealed no notable abnormalities in liver function markers but did demonstrate statistically significant changes in urea (p = 0.028) and creatinine (p = 0.003) levels. Ultrasonography and computed tomography showed multiple liver nodules with characteristics resembling HCC. Serial imaging screening and more extended observations revealed that all animals eventually developed tumors. Histopathological confirmation at 15– 22 weeks post-induction revealed that all intervened swine developed multiple nodules of well-differentiated HCC and some with hepatic angiosarcoma.<br/><strong>Conclusion:</strong> This study successfully generated HCC in conventional domestic swine with a DENA and PB combination. This investigation required at least 15 months to develop tumors. This model will be beneficial for future investigations of HCC in large animals.<br/><br/><strong>Keywords:</strong> carcinogenesis, large animal model, hepatocellular carcinoma, domestic swine, DENA induction<br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140300833","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}
Purpose: Consensus molecular subtypes (CMS) are mainly used for biological interpretability and clinical stratification of colorectal cancer (CRC) in primary tumors (PT) but few in metastases. The heterogeneity of CMS distribution in metastases and the concordance of CMS between PT and metastases still lack sufficient study. We used CMS to classify CRC metastases and combine it with histopathological analysis to explore differences between PT and distant metastases. Patients and Methods: We obtained gene expression profiles for 942 PT samples from TCGA database (n=376) and GEO database (n=566), as well as 442 metastasis samples from GEO database. Among these, 765 PT samples and 442 metastasis samples were confidently identified with CMS using the “CMS classifier” and enrolled for analysis. Clinicopathological manifestation and CMS classification of CRC metastases were assessed with data from GEO, TCGA, and cBioPortal. Overall, 105 PT-metastasis pairs were extracted from 10 GEO datasets to assess CMS concordance. Tumor microenvironment (TME) features between PT and metastases were analyzed by immune-stromal infiltration with ESTIMATE and xCell algorithms. Finally, TME features were validated with multiplex immunohistochemistry in 27 PT-metastasis pairs we retrospectively collected. Results: Up to 64% of CRC metastases exhibited concordant CMS groups with matched PT, and the TME of metastases was similar to that of PT. For most common distant metastases, liver metastases were predominantly CMS2 and lung and peritoneal metastases were mainly CMS4, highlighting “seed” of tumor cells of different CMS groups had a preference for metastasis to “soil” of specific organs. Compared with PT, cancer-associated fibroblasts (CAF) reduced in liver metastases, CD4+T cells and M2-like macrophages increased in lung metastases, and M2-like macrophages and CAF increased in peritoneal metastases. Conclusion: Our findings underscore the importance of CMS-guided specific organ monitoring and treatment post-primary tumor surgery for patients. Differences in immune-stromal infiltration among different metastases provide targeted therapeutic opportunities for metastatic CRC.
{"title":"Seed and Soil: Consensus Molecular Subgroups (CMS) and Tumor Microenvironment Features Between Primary Lesions and Metastases of Different Organ Sites in Colorectal Cancer","authors":"Qingqing Luo, Yibo Quan, Wei Liu, Zixin Wu, Wenjing Qiu, Wenlong Liang, Ping Yang, Qing Huang, Guanwei Li, Jianchang Wei, Qiang Wang, Fei Shen, Wanglin Li, Feng He, Jie Cao","doi":"10.2147/cmar.s441675","DOIUrl":"https://doi.org/10.2147/cmar.s441675","url":null,"abstract":"<strong>Purpose:</strong> Consensus molecular subtypes (CMS) are mainly used for biological interpretability and clinical stratification of colorectal cancer (CRC) in primary tumors (PT) but few in metastases. The heterogeneity of CMS distribution in metastases and the concordance of CMS between PT and metastases still lack sufficient study. We used CMS to classify CRC metastases and combine it with histopathological analysis to explore differences between PT and distant metastases.<br/><strong>Patients and Methods:</strong> We obtained gene expression profiles for 942 PT samples from TCGA database (n=376) and GEO database (n=566), as well as 442 metastasis samples from GEO database. Among these, 765 PT samples and 442 metastasis samples were confidently identified with CMS using the “CMS classifier” and enrolled for analysis. Clinicopathological manifestation and CMS classification of CRC metastases were assessed with data from GEO, TCGA, and cBioPortal. Overall, 105 PT-metastasis pairs were extracted from 10 GEO datasets to assess CMS concordance. Tumor microenvironment (TME) features between PT and metastases were analyzed by immune-stromal infiltration with ESTIMATE and xCell algorithms. Finally, TME features were validated with multiplex immunohistochemistry in 27 PT-metastasis pairs we retrospectively collected.<br/><strong>Results:</strong> Up to 64% of CRC metastases exhibited concordant CMS groups with matched PT, and the TME of metastases was similar to that of PT. For most common distant metastases, liver metastases were predominantly CMS2 and lung and peritoneal metastases were mainly CMS4, highlighting “seed” of tumor cells of different CMS groups had a preference for metastasis to “soil” of specific organs. Compared with PT, cancer-associated fibroblasts (CAF) reduced in liver metastases, CD4+T cells and M2-like macrophages increased in lung metastases, and M2-like macrophages and CAF increased in peritoneal metastases.<br/><strong>Conclusion:</strong> Our findings underscore the importance of CMS-guided specific organ monitoring and treatment post-primary tumor surgery for patients. Differences in immune-stromal infiltration among different metastases provide targeted therapeutic opportunities for metastatic CRC.<br/><br/><strong>Keywords:</strong> colorectal cancer, primary tumors, metastases, consensus molecular subtypes, tumor microenvironment<br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140165358","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}
Background: PERP, a member of the peripheral myelin protein gene family, is a new therapeutic target in cancer. The relationships between PERP and immune cell infiltration in lung cancer have not been studied. Therefore, the role of PERP in the tumour microenvironment (TME) of lung cancer needs to be further explored. Methods: In this study, we explored the association between PERP expression and clinical characteristics by analysing data from the TCGA database. Cox regression and Kaplan‒Meier methods were used to investigate the relationship between the expression of PERP and overall survival in patients with lung adenocarcinoma (LUAD). The relationship between PERP expression and the degree of infiltration of specific immune cell subsets in LUAD was evaluated using the TIMER database and GEPIA. We also performed GO enrichment analysis and KEGG enrichment analysis to reveal genes coexpressed with PERP using the Coexpedia database. Finally, we verified the expression and function of PERP in LUAD tissues and the A549 cell line by RT‒PCR, Western blot, CCK-8, IHC, and wound healing assays. The mouse model was used to study the in vivo effects of PERP. Results: According to our results, PERP expression was significantly higher in LUAD tissues and associated with the clinical characteristics of the disease. Survival was independently associated with PERP in LUAD patients. We further verified that PERP might regulate B-cell infiltration in LUAD to affect the prognosis of LUAD. To identify PERP-related signalling pathways in LUAD, we performed a genome-aggregation analysis (GSEA) between low and high PERP expression datasets. LUAD cells express higher levels of PERP than paracarcinoma cells, and PERP inhibits the proliferation and metastasis of A549 cells through apoptosis. Conclusion: PERP may affect the prognosis of lung adenocarcinoma by inhibiting apoptosis and is associated with immune cell infiltration.
{"title":"PERP May Affect the Prognosis of Lung Adenocarcinoma by Inhibiting Apoptosis","authors":"Zhongxiang Liu, Shuhua Han, Yuhong Luo, Zhangyan Zhao, Lingyu Ni, Linlin Chai, Haicheng Tang","doi":"10.2147/cmar.s443490","DOIUrl":"https://doi.org/10.2147/cmar.s443490","url":null,"abstract":"<strong>Background:</strong> PERP, a member of the peripheral myelin protein gene family, is a new therapeutic target in cancer. The relationships between PERP and immune cell infiltration in lung cancer have not been studied. Therefore, the role of PERP in the tumour microenvironment (TME) of lung cancer needs to be further explored.<br/><strong>Methods:</strong> In this study, we explored the association between PERP expression and clinical characteristics by analysing data from the TCGA database. Cox regression and Kaplan‒Meier methods were used to investigate the relationship between the expression of PERP and overall survival in patients with lung adenocarcinoma (LUAD). The relationship between PERP expression and the degree of infiltration of specific immune cell subsets in LUAD was evaluated using the TIMER database and GEPIA. We also performed GO enrichment analysis and KEGG enrichment analysis to reveal genes coexpressed with PERP using the Coexpedia database. Finally, we verified the expression and function of PERP in LUAD tissues and the A549 cell line by RT‒PCR, Western blot, CCK-8, IHC, and wound healing assays. The mouse model was used to study the in vivo effects of PERP.<br/><strong>Results:</strong> According to our results, PERP expression was significantly higher in LUAD tissues and associated with the clinical characteristics of the disease. Survival was independently associated with PERP in LUAD patients. We further verified that PERP might regulate B-cell infiltration in LUAD to affect the prognosis of LUAD. To identify PERP-related signalling pathways in LUAD, we performed a genome-aggregation analysis (GSEA) between low and high PERP expression datasets. LUAD cells express higher levels of PERP than paracarcinoma cells, and PERP inhibits the proliferation and metastasis of A549 cells through apoptosis.<br/><strong>Conclusion:</strong> PERP may affect the prognosis of lung adenocarcinoma by inhibiting apoptosis and is associated with immune cell infiltration.<br/><br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140165357","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}
Purpose: Elevated serum sialic acid (SA) is one of the indicators of poor prognosis in various malignant tumors. This study intends to determine the relationship between serum SA levels and survival prognosis in nasopharyngeal carcinoma (NPC). Patients and Methods: From 2014 to 2016, NPC patients with no distance metastasis undergoing intensity-modulated radiotherapy (IMRT) were retrospectively analyzed. The serum SA levels before initial treatment were measured, and an optimal cut-off level was determined by X-tile software. A propensity score matching (PSM) technique was applied to reduce intergroup differences between the low serum SA level group and the high serum SA level group. Chi-square tests were utilized for comparing intergroup differences, Kaplan-Meier approach was utilized for plotting survival curves, and univariate and multivariate Cox proportional hazards regression models were employed for analyzing prognostic factors. Results: Overall, 293 NPC patients with no distance metastasis were included. The optimal cut-off level of serum SA was 65.10 mg/dl. The baseline levels after PSM were more balanced compared to those before PSM. Survival analysis showed that the locoregional relapse-free survival (LRRFS, p=0.010), distant metastasis–free survival (DMFS, p=0.014), progression-free survival (PFS, p=0.009), and overall survival (OS, p=0.015) survival curves of the low serum SA level group and high serum SA level group were statistically significant differences. Univariate analysis showed that American Joint Committee on Cancer (AJCC) stage, T stage, N stage, neoadjuvant chemotherapy (NC), and serum SA expression level were factors influencing the prognosis of NPC patients. Multivariate analysis showed that high serum SA expression level was related to worse PFS and OS in NPC patients with no distance metastasis. Conclusion: High serum SA level (SA > 65.10 mg/dl) before treatment is associated to poor survival outcomes in NPC and is an independent adverse prognostic factor in NPC patients with no distance metastasis.
目的：血清硅酸（SA）升高是各种恶性肿瘤预后不良的指标之一。本研究旨在确定血清SA水平与鼻咽癌（NPC）生存预后之间的关系：回顾性分析2014年至2016年接受调强放射治疗（IMRT）的无远处转移的鼻咽癌患者。测量初始治疗前的血清SA水平，并通过X-tile软件确定最佳临界水平。采用倾向得分匹配（PSM）技术来减少低血清SA水平组和高血清SA水平组之间的组间差异。比较组间差异采用卡普兰-梅耶法（Kaplan-Meier approach）绘制生存曲线，分析预后因素采用单变量和多变量考克斯比例危险回归模型：结果：共纳入了 293 例无远处转移的鼻咽癌患者。血清 SA 的最佳临界水平为 65.10 mg/dl。与 PSM 前相比，PSM 后的基线水平更为均衡。生存分析显示，低血清 SA 水平组和高血清 SA 水平组的无局部复发生存（LRRFS，P=0.010）、无远处转移生存（DMFS，P=0.014）、无进展生存（PFS，P=0.009）和总生存（OS，P=0.015）生存曲线差异有统计学意义。单变量分析显示，美国癌症联合委员会（AJCC）分期、T期、N期、新辅助化疗（NC）和血清SA表达水平是影响鼻咽癌患者预后的因素。多变量分析显示，在无远处转移的鼻咽癌患者中，高血清SA表达水平与较差的PFS和OS有关：结论：治疗前的高血清SA水平（SA 65.10 mg/dl）与鼻咽癌患者的不良生存预后有关，并且是无远处转移的鼻咽癌患者的独立不良预后因素。
{"title":"The Prognostic Value of Serum Sialic Acid in Patients with Nasopharyngeal Carcinoma: A Propensity Score Matching Study","authors":"Zetan Chen, Gang Wu, Xiangying Lin, Xiaopeng Huang, Shuai Zhang, Kaihua Chen, Zhongguo Liang, Xiaodong Zhu","doi":"10.2147/cmar.s448238","DOIUrl":"https://doi.org/10.2147/cmar.s448238","url":null,"abstract":"<strong>Purpose:</strong> Elevated serum sialic acid (SA) is one of the indicators of poor prognosis in various malignant tumors. This study intends to determine the relationship between serum SA levels and survival prognosis in nasopharyngeal carcinoma (NPC).<br/><strong>Patients and Methods:</strong> From 2014 to 2016, NPC patients with no distance metastasis undergoing intensity-modulated radiotherapy (IMRT) were retrospectively analyzed. The serum SA levels before initial treatment were measured, and an optimal cut-off level was determined by X-tile software. A propensity score matching (PSM) technique was applied to reduce intergroup differences between the low serum SA level group and the high serum SA level group. Chi-square tests were utilized for comparing intergroup differences, Kaplan-Meier approach was utilized for plotting survival curves, and univariate and multivariate Cox proportional hazards regression models were employed for analyzing prognostic factors.<br/><strong>Results:</strong> Overall, 293 NPC patients with no distance metastasis were included. The optimal cut-off level of serum SA was 65.10 mg/dl. The baseline levels after PSM were more balanced compared to those before PSM. Survival analysis showed that the locoregional relapse-free survival (LRRFS, p=0.010), distant metastasis–free survival (DMFS, p=0.014), progression-free survival (PFS, p=0.009), and overall survival (OS, p=0.015) survival curves of the low serum SA level group and high serum SA level group were statistically significant differences. Univariate analysis showed that American Joint Committee on Cancer (AJCC) stage, T stage, N stage, neoadjuvant chemotherapy (NC), and serum SA expression level were factors influencing the prognosis of NPC patients. Multivariate analysis showed that high serum SA expression level was related to worse PFS and OS in NPC patients with no distance metastasis.<br/><strong>Conclusion:</strong> High serum SA level (SA > 65.10 mg/dl) before treatment is associated to poor survival outcomes in NPC and is an independent adverse prognostic factor in NPC patients with no distance metastasis.<br/><br/><strong>Keywords:</strong> serum sialic acid, nasopharyngeal carcinoma, prognosis, propensity score matching<br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140165351","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}
Purpose: Cetuximab (CET) combined with chemotherapy significantly improved the survival in RAS and RAF wild-type metastatic colorectal cancer (mCRC) patients, while clinical evidence was lacking on the use of maintenance therapy (MT). The study aimed to explore the role of maintenance therapy following Cetuximab + chemotherapy and the optimal Cetuximab-based maintenance therapy regimen. Patients and Methods: We retrospectively reviewed data on the efficacy and safety of CET-based MT in patients with mCRC who achieved disease control after induction therapy. Results: Eighty-one patients with mCRC who achieved disease control after CET + chemotherapy induction were enrolled. Overall median progression-free survival (PFS) was 10.5 (95% CI = 8.8– 12.2) months and median maintenance/observation PFS (mnPFS) was 6.0 (95% CI = 5.0– 7.0) months. Among these 81 patients, 61 patients were prescribed MT (CET alone for 21 patients and CET + chemotherapy for 40 patients). Median PFS and mnPFS in the MT group were significantly longer than those for the non-MT group. Different MT regimens did not affect PFS and mnPFS significantly. Univariate and multivariate analysis demonstrated MT, complete response/partial response during induction therapy, and absence of peritoneal metastasis to be positively associated with longer PFS and mnPFS. Treatment-related adverse events (AEs) were tolerable during MT, and AE-related deaths were not observed. Conclusion: MT with CET or CET + chemotherapy was an appropriate option following initial induction chemotherapy for patients with RAS and RAF wild-type mCRC. This strategy endowed survival benefits and a tolerable safety profile.
{"title":"Efficacy and Safety of Maintenance Therapy Using Cetuximab in Patients with Metastatic Colorectal Cancer: Retrospective Study","authors":"Tiantian Xuan, Zhanmei Wang, Sibo Meng, Jiaxin Li, Jisheng Li, Fangli Cao, Linli Qu","doi":"10.2147/cmar.s443666","DOIUrl":"https://doi.org/10.2147/cmar.s443666","url":null,"abstract":"<strong>Purpose:</strong> Cetuximab (CET) combined with chemotherapy significantly improved the survival in RAS and RAF wild-type metastatic colorectal cancer (mCRC) patients, while clinical evidence was lacking on the use of maintenance therapy (MT). The study aimed to explore the role of maintenance therapy following Cetuximab + chemotherapy and the optimal Cetuximab-based maintenance therapy regimen.<br/><strong>Patients and Methods:</strong> We retrospectively reviewed data on the efficacy and safety of CET-based MT in patients with mCRC who achieved disease control after induction therapy.<br/><strong>Results:</strong> Eighty-one patients with mCRC who achieved disease control after CET + chemotherapy induction were enrolled. Overall median progression-free survival (PFS) was 10.5 (95% CI = 8.8– 12.2) months and median maintenance/observation PFS (mnPFS) was 6.0 (95% CI = 5.0– 7.0) months. Among these 81 patients, 61 patients were prescribed MT (CET alone for 21 patients and CET + chemotherapy for 40 patients). Median PFS and mnPFS in the MT group were significantly longer than those for the non-MT group. Different MT regimens did not affect PFS and mnPFS significantly. Univariate and multivariate analysis demonstrated MT, complete response/partial response during induction therapy, and absence of peritoneal metastasis to be positively associated with longer PFS and mnPFS. Treatment-related adverse events (AEs) were tolerable during MT, and AE-related deaths were not observed.<br/><strong>Conclusion:</strong> MT with CET or CET + chemotherapy was an appropriate option following initial induction chemotherapy for patients with RAS and RAF wild-type mCRC. This strategy endowed survival benefits and a tolerable safety profile.<br/><br/><strong>Keywords:</strong> colorectal cancer, maintenance therapy, cetuximab, RAS and RAF wild-type, targeted therapy<br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140165406","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}
Fei Cai, Di Wu, Junling Liu, Shuxi Song, Jingyu Li, Zhendong Zheng, Long Xu
Objective: Cystic brain metastases (BMs) are rare in small cell lung cancer (SCLC), and there are limited data on the treatment and prognosis of cystic BMs. Whole brain radiotherapy has been the mainstay for BMs since several years. Immune checkpoint inhibitors in extensive stage small cell lung cancer (ES-SCLC) have been shown to be suitable for patients who experienced better overall survival and progress-free survival and have been approved as the first-line treatment for ES-SCLC. In this report, we described two ES-SCLC patients developed cystic BMs after immunotherapy, after which the patients continued to treat the primary lesion with immune checkpoint inhibitors and the cystic BMs with radiotherapy. Case Description: Two male patients were diagnosed with ES-SCLC at the first admission and were subsequently treated with immunotherapy plus platinum therapy, during which cystic BMs developed. One patient received whole brain radiotherapy and the other received whole brain radiotherapy and Gamma knife radiosurgery (GKRS). Immunotherapy was continued after the brain lesions were controlled. It has been 33 months since the first patient was diagnosed and is now in stable condition. The other patient achieved an overall survival of 30 months. Conclusion: This report describes two patients with cystic brain metastases in ES-SCLC. Whole brain radiotherapy has a good effect on local control of cystic brain metastases in small cell lung cancer and can significantly improve the symptoms of patients. At the same time, we treat immunotherapy as the first-line treatment, and then perform cross-immunotherapy after disease progression, combined with anti-vascular targeting drugs. The patient did not develop severe iRAEs.
{"title":"Extensive Stage Small-Cell Lung Cancer with Cystic Brain Metastases: A Report of Two Cases","authors":"Fei Cai, Di Wu, Junling Liu, Shuxi Song, Jingyu Li, Zhendong Zheng, Long Xu","doi":"10.2147/cmar.s449841","DOIUrl":"https://doi.org/10.2147/cmar.s449841","url":null,"abstract":"<strong>Objective:</strong> Cystic brain metastases (BMs) are rare in small cell lung cancer (SCLC), and there are limited data on the treatment and prognosis of cystic BMs. Whole brain radiotherapy has been the mainstay for BMs since several years. Immune checkpoint inhibitors in extensive stage small cell lung cancer (ES-SCLC) have been shown to be suitable for patients who experienced better overall survival and progress-free survival and have been approved as the first-line treatment for ES-SCLC. In this report, we described two ES-SCLC patients developed cystic BMs after immunotherapy, after which the patients continued to treat the primary lesion with immune checkpoint inhibitors and the cystic BMs with radiotherapy.<br/><strong>Case Description:</strong> Two male patients were diagnosed with ES-SCLC at the first admission and were subsequently treated with immunotherapy plus platinum therapy, during which cystic BMs developed. One patient received whole brain radiotherapy and the other received whole brain radiotherapy and Gamma knife radiosurgery (GKRS). Immunotherapy was continued after the brain lesions were controlled. It has been 33 months since the first patient was diagnosed and is now in stable condition. The other patient achieved an overall survival of 30 months.<br/><strong>Conclusion:</strong> This report describes two patients with cystic brain metastases in ES-SCLC. Whole brain radiotherapy has a good effect on local control of cystic brain metastases in small cell lung cancer and can significantly improve the symptoms of patients. At the same time, we treat immunotherapy as the first-line treatment, and then perform cross-immunotherapy after disease progression, combined with anti-vascular targeting drugs. The patient did not develop severe iRAEs.<br/><br/><strong>Keywords:</strong> ES-SCLC, immunotherapy, cystic BMs, cross-line immunotherapy<br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140151587","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}
Purpose: Immune checkpoint inhibitors (ICIs) have significantly improved the outcomes of patients with cancer; however, these agents may initiate immune-related adverse events (irAEs). Previous studies have demonstrated a robust correlation between disease prognosis and the occurrence of irAEs, specifically skin or endocrine irAEs. Herein, we aimed to evaluate the correlation between irAE-related adrenal insufficiency (AI) and ICI treatment efficacy. Patients and methods: Patients diagnosed with gastrointestinal, respiratory, head and neck, urological, skin and gynecologic cancers treated with anti-programmed cell death 1 (PD-1)/anti-programmed cell death ligand 1 (PD-L1) antibody as monotherapy or combined therapy (combined with chemotherapy or targeted therapy) were divided into irAE-A (patients with irAE-related AI), irAE-B (patients with other irAEs) and non-irAE groups. Immunotherapy efficacy was assessed based on the disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Survival probabilities were estimated using the Kaplan–Meier method with the log–rank test. Results: Of the 192 patients enrolled in our study, 17 developed irAE-related AI and 83 developed other irAEs. The DCR of the irAE-A and irAE-B groups were higher than that of the non-irAE group (P< 0.05). Multiple extended Cox regression analyses showed that irAE status (irAE-A vs non-irAE, P=0.008; irAE-B vs non-irAE, P=0.020), Eastern Cooperative Oncology Group (ECOG) status (P=0.045), tumor-node-metastasis (TNM) stage (P=0.000), and treatment line (P=0.002) were independent predictors of PFS. Contrarily, irAE status (irAE-A vs non-irAE, P=0.009; irAE-B vs non-irAE, P=0.013), ECOG status (P=0.007), TNM stage (P=0.035), treatment line (P=0.001) and treatment modality (P=0.008) were independent predictors for OS. Conclusion: IrAE-related AI was significantly associated with ICI treatment efficacy in patients with cancer, which could be a potentially predictable marker. Due to the destruction of adrenal tissue by T cells with enhanced activity, AI reflects enhanced T cell activity to some extent.
目的：免疫检查点抑制剂（ICIs）大大改善了癌症患者的预后；然而，这些药物可能引发免疫相关不良事件（irAEs）。以往的研究表明，疾病预后与irAEs（尤其是皮肤或内分泌irAEs）的发生之间存在密切的相关性。在此，我们旨在评估与irAE相关的肾上腺功能不全（AI）与ICI疗效之间的相关性：将胃肠道癌、呼吸系统癌、头颈部癌、泌尿系统癌、皮肤癌和妇科癌症患者分为irAE-A组（irAE相关肾上腺功能不全患者）、irAE-B组（其他irAEs患者）和非irAE组，使用抗程序性细胞死亡1（PD-1）/抗程序性细胞死亡配体1（PD-L1）抗体进行单药治疗或联合治疗（联合化疗或靶向治疗）。免疫疗法的疗效根据疾病控制率（DCR）、无进展生存期（PFS）和总生存期（OS）进行评估。采用卡普兰-梅耶法和对数秩检验估算生存概率：在192例参与研究的患者中，17例出现了与虹膜AE相关的AI，83例出现了其他虹膜AE。irAE-A组和irAE-B组的DCR高于非irAE组（P< 0.05）。多重扩展 Cox 回归分析显示，irAE 状态（irAE-A vs 非 irAE，P=0.008；irAE-B vs 非 irAE，P=0.020）、东部合作肿瘤学组（ECOG）状态（P=0.045）、肿瘤结节-转移（TNM）分期（P=0.000）和治疗线（P=0.002）是 PFS 的独立预测因素。相反，irAE状态（irAE-A vs nonirAE，P=0.009；irAE-B vs nonirAE，P=0.013）、ECOG状态（P=0.007）、TNM分期（P=0.035）、治疗线（P=0.001）和治疗方式（P=0.008）是OS的独立预测因素：结论：IrAE相关的AI与癌症患者的ICI疗效明显相关，这可能是一个潜在的可预测标志物。关键词：内分泌不良事件；恶性肿瘤；单克隆抗体治疗；免疫相关副作用；疗效
{"title":"Immune-Related Adverse Event-Related Adrenal Insufficiency Mediates Immune Checkpoint Inhibitors Efficacy in Cancer Treatment","authors":"Shasha Zhang, Jianhua Wu, Yue Zhao, Jingjing Zhang, Xiaoyun Zhang, Chensi Wu, Zhidong Zhang, Zhanjun Guo","doi":"10.2147/cmar.s444916","DOIUrl":"https://doi.org/10.2147/cmar.s444916","url":null,"abstract":"<strong>Purpose:</strong> Immune checkpoint inhibitors (ICIs) have significantly improved the outcomes of patients with cancer; however, these agents may initiate immune-related adverse events (irAEs). Previous studies have demonstrated a robust correlation between disease prognosis and the occurrence of irAEs, specifically skin or endocrine irAEs. Herein, we aimed to evaluate the correlation between irAE-related adrenal insufficiency (AI) and ICI treatment efficacy.<br/><strong>Patients and methods:</strong> Patients diagnosed with gastrointestinal, respiratory, head and neck, urological, skin and gynecologic cancers treated with anti-programmed cell death 1 (PD-1)/anti-programmed cell death ligand 1 (PD-L1) antibody as monotherapy or combined therapy (combined with chemotherapy or targeted therapy) were divided into irAE-A (patients with irAE-related AI), irAE-B (patients with other irAEs) and non-irAE groups. Immunotherapy efficacy was assessed based on the disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Survival probabilities were estimated using the Kaplan–Meier method with the log–rank test.<br/><strong>Results:</strong> Of the 192 patients enrolled in our study, 17 developed irAE-related AI and 83 developed other irAEs. The DCR of the irAE-A and irAE-B groups were higher than that of the non-irAE group (<em>P</em>< 0.05). Multiple extended Cox regression analyses showed that irAE status (irAE-A vs non-irAE, <em>P</em>=0.008; irAE-B vs non-irAE, <em>P</em>=0.020), Eastern Cooperative Oncology Group (ECOG) status (<em>P</em>=0.045), tumor-node-metastasis (TNM) stage (<em>P</em>=0.000), and treatment line (<em>P</em>=0.002) were independent predictors of PFS. Contrarily, irAE status (irAE-A vs non-irAE, <em>P</em>=0.009; irAE-B vs non-irAE, <em>P</em>=0.013), ECOG status (<em>P</em>=0.007), TNM stage (<em>P</em>=0.035), treatment line (<em>P</em>=0.001) and treatment modality (<em>P</em>=0.008) were independent predictors for OS.<br/><strong>Conclusion:</strong> IrAE-related AI was significantly associated with ICI treatment efficacy in patients with cancer, which could be a potentially predictable marker. Due to the destruction of adrenal tissue by T cells with enhanced activity, AI reflects enhanced T cell activity to some extent.<br/><br/><strong>Keywords:</strong> endocrine adverse event, malignancies, monoclonal antibody therapy, immune-related side effects, treatment efficacy<br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140126116","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}
Tao Xue, Hongbin Yu, Wenming Feng, Yao Wang, Shiyong Wu, Lili Wang, Peiqin Zhu, Jianming Guan, Quan Sun
Background: The presence of macrovascular invasion (MVI) is associated with poor prognosis in advanced hepatocellular carcinoma (HCC). This study aims to evaluate the efficacy and safety of Cinobufacini therapy via hepatic arterial infusion (HAI) in advanced HCC patients with MVI. Methods: The clinical records of 130 consecutive patients with unresectable advanced HCC and MVI who had received Cinobufacini or cisplatin plus 5-fluorouracil (CF) treatment via HAI were retrospectively analyzed. The therapeutic efficacy, overall survival (OS), progression-free survival (PFS), and adverse events were compared between the two treatment groups. Results: The Cinobufacini group demonstrated significant curative effects on treatment via HAI compared with the CF group, including the objective response rate (44.9% vs 27.9%, P=0.048), the median OS (14.8 months vs 11.1 months, P=0.010), and the median PFS (10.3 months vs 6.0 months, P=0.006). Result in subgroup analysis of portal vein invasion grade supported the efficacy in Cinobufacini treatment, especially in the median OS of Vp1-2 (18.3 months vs 14.3 months, P=0.043) and Vp3 (15.0 months vs 11.4 months, P=0.046), as well as the median PFS of Vp1-2 (14.8 months vs 10.2 months, P=0.028) and Vp3 (10.8 months vs 6.6 months, P=0.033) compared with CF treatment. Cox proportional hazards model and forest plot analysis of factors confirmed the survival benefit from HAI with Cinobufacini over CF (hazard ratio [HR], 0.61; 95% CI: 0.40– 0.91; P=0.010). Multivariable analysis identified portal vein invasion grade (Vp4; HR, 1.78; 95% CI: 1.03– 2.16; P=0.032) and AFP (> 1000; HR, 1.61; 95% CI: 1.08– 1.91; P=0.039) as the independent factors for prognosis. Moreover, the total incidence of adverse events in the Cinobufacini group was significantly lower than in the CF group (60.9% vs 82.0%, P=0.009). Conclusion: Cinobufacini therapy via HAI is a viable strategy for curing advanced HCC with MVI, due to prolonged survival and a superior safety profile.
背景：大血管侵犯（MVI）的存在与晚期肝细胞癌（HCC）的不良预后有关。本研究旨在评估通过肝动脉输注（HAI）对伴有大血管侵犯的晚期 HCC 患者进行西诺布卡尼治疗的有效性和安全性：方法：回顾性分析了130例连续接受Cinobufacini或顺铂加5-氟尿嘧啶（CF）肝动脉输注治疗的不可切除晚期HCC合并MVI患者的临床记录。比较了两组患者的疗效、总生存期（OS）、无进展生存期（PFS）和不良反应：结果：与 CF 组相比，Cinobufacini 组通过 HAI 治疗取得了显著的疗效，包括客观反应率（44.9% vs 27.9%，P=0.048）、中位 OS（14.8 个月 vs 11.1 个月，P=0.010）和中位 PFS（10.3 个月 vs 6.0 个月，P=0.006）。门静脉侵犯分级亚组分析结果支持西诺巴昔尼治疗的疗效，尤其是与CF治疗相比，Vp1-2（18.3个月 vs 14.3个月，P=0.043）和Vp3（15.0个月 vs 11.4个月，P=0.046）的中位OS，以及Vp1-2（14.8个月 vs 10.2个月，P=0.028）和Vp3（10.8个月 vs 6.6个月，P=0.033）的中位PFS。Cox比例危险模型和因素森林图分析证实，与CF相比，使用西诺巴昔尼进行HAI治疗可提高生存率（危险比[HR]，0.61；95% CI：0.40- 0.91；P=0.010）。多变量分析发现，门静脉侵犯分级（Vp4；HR，1.78；95% CI：1.03- 2.16；P=0.032）和 AFP（>；1000；HR，1.61；95% CI：1.08- 1.91；P=0.039）是影响预后的独立因素。此外，西诺布法西尼组的不良反应总发生率明显低于CF组（60.9% vs 82.0%，P=0.009）：结论：通过HAI进行西诺布卡尼治疗是治愈伴有MVI的晚期HCC的一种可行策略，因为它能延长患者的生存期，而且安全性更高。
{"title":"Efficacy and Safety of Hepatic Arterial Infusion Therapy with Cinobufacini in Advanced Hepatocellular Carcinoma with Macrovascular Invasion: A Retrospective Cohort Study","authors":"Tao Xue, Hongbin Yu, Wenming Feng, Yao Wang, Shiyong Wu, Lili Wang, Peiqin Zhu, Jianming Guan, Quan Sun","doi":"10.2147/cmar.s440017","DOIUrl":"https://doi.org/10.2147/cmar.s440017","url":null,"abstract":"<strong>Background:</strong> The presence of macrovascular invasion (MVI) is associated with poor prognosis in advanced hepatocellular carcinoma (HCC). This study aims to evaluate the efficacy and safety of Cinobufacini therapy via hepatic arterial infusion (HAI) in advanced HCC patients with MVI.<br/><strong>Methods:</strong> The clinical records of 130 consecutive patients with unresectable advanced HCC and MVI who had received Cinobufacini or cisplatin plus 5-fluorouracil (CF) treatment via HAI were retrospectively analyzed. The therapeutic efficacy, overall survival (OS), progression-free survival (PFS), and adverse events were compared between the two treatment groups.<br/><strong>Results:</strong> The Cinobufacini group demonstrated significant curative effects on treatment via HAI compared with the CF group, including the objective response rate (44.9% vs 27.9%, <em>P</em>=0.048), the median OS (14.8 months vs 11.1 months, <em>P</em>=0.010), and the median PFS (10.3 months vs 6.0 months, <em>P</em>=0.006). Result in subgroup analysis of portal vein invasion grade supported the efficacy in Cinobufacini treatment, especially in the median OS of Vp1-2 (18.3 months vs 14.3 months, <em>P</em>=0.043) and Vp3 (15.0 months vs 11.4 months, <em>P</em>=0.046), as well as the median PFS of Vp1-2 (14.8 months vs 10.2 months, <em>P</em>=0.028) and Vp3 (10.8 months vs 6.6 months, <em>P</em>=0.033) compared with CF treatment. Cox proportional hazards model and forest plot analysis of factors confirmed the survival benefit from HAI with Cinobufacini over CF (hazard ratio [HR], 0.61; 95% CI: 0.40– 0.91; <em>P</em>=0.010). Multivariable analysis identified portal vein invasion grade (Vp4; HR, 1.78; 95% CI: 1.03– 2.16; <em>P</em>=0.032) and AFP (> 1000; HR, 1.61; 95% CI: 1.08– 1.91; <em>P</em>=0.039) as the independent factors for prognosis. Moreover, the total incidence of adverse events in the Cinobufacini group was significantly lower than in the CF group (60.9% vs 82.0%, <em>P</em>=0.009).<br/><strong>Conclusion:</strong> Cinobufacini therapy via HAI is a viable strategy for curing advanced HCC with MVI, due to prolonged survival and a superior safety profile.<br/><br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140126465","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}
Background: The Sirtuin (SIRT) family consists of seven evolutionary conserved NAD-dependent deacetylases that play important roles in various cancers, including breast cancer (BC). SIRTs expression has been reported to have prognostic value in BC, but these studies used limited sample size and yielded inconsistent conclusions. This study evaluated the association of SIRT3 and other SIRT family members with survival and neoadjuvant chemotherapy outcomes. Methods: BC patients’ data was obtained from the TCGA-BRCA, METABRIC and GEO databases, comprising 4336 samples. SIRTs expression and overall survival (OS) were analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. SIRT3 expression levels were compared between pathologic complete response (pCR) and non-pCR groups after neoadjuvant chemotherapy in triple-negative breast cancer (TNBC). Protein-protein interaction networks were constructed using the STRING database. Gene set enrichment analysis (GSEA) was performed to explore potential functions of SIRT3. Results: Through systematic analysis of SIRTs expression and OS of BC using three independent cohorts: TCGA-BRCA, METABRIC and GSE16446, we found that high SIRT3 expression was significantly associated with worse OS in TNBC in the TCGA-BRCA cohort, which was validated in the METABRIC and GSE16446 cohorts. SIRT3 expression was correlated with BC subtypes and American Joint Committee on Cancer (AJCC) T stage, but not with age-at-diagnosis, race, or tumor stage. Moreover, TNBC patients with higher SIRT3 expression had lower pCR rates after neoadjuvant chemotherapy (p = 6.40e-03) and SIRT3 expression was significantly lower in the pCR group than in the non-pCR group in TNBC (p = 4.2e-03). GSEA indicated that SIRT3 was involved in drug-related pathways such as oxidative phosphorylation, metabolism of xenobiotics by cytochrome P450, and drug metabolism. Conclusion: Our study suggests that SIRT3 is a potential biomarker for both OS and neoadjuvant chemosensitivity in TNBC. It may also assist in selecting suitable candidates and treatment options for TNBC patients.
{"title":"SIRT3 Expression Predicts Overall Survival and Neoadjuvant Chemosensitivity in Triple-Negative Breast Cancer","authors":"Lvwen Ning, Ni Xie","doi":"10.2147/cmar.s445248","DOIUrl":"https://doi.org/10.2147/cmar.s445248","url":null,"abstract":"<strong>Background:</strong> The Sirtuin (SIRT) family consists of seven evolutionary conserved NAD-dependent deacetylases that play important roles in various cancers, including breast cancer (BC). SIRTs expression has been reported to have prognostic value in BC, but these studies used limited sample size and yielded inconsistent conclusions. This study evaluated the association of SIRT3 and other SIRT family members with survival and neoadjuvant chemotherapy outcomes.<br/><strong>Methods:</strong> BC patients’ data was obtained from the TCGA-BRCA, METABRIC and GEO databases, comprising 4336 samples. SIRTs expression and overall survival (OS) were analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. SIRT3 expression levels were compared between pathologic complete response (pCR) and non-pCR groups after neoadjuvant chemotherapy in triple-negative breast cancer (TNBC). Protein-protein interaction networks were constructed using the STRING database. Gene set enrichment analysis (GSEA) was performed to explore potential functions of SIRT3.<br/><strong>Results:</strong> Through systematic analysis of SIRTs expression and OS of BC using three independent cohorts: TCGA-BRCA, METABRIC and GSE16446, we found that high SIRT3 expression was significantly associated with worse OS in TNBC in the TCGA-BRCA cohort, which was validated in the METABRIC and GSE16446 cohorts. SIRT3 expression was correlated with BC subtypes and American Joint Committee on Cancer (AJCC) T stage, but not with age-at-diagnosis, race, or tumor stage. Moreover, TNBC patients with higher SIRT3 expression had lower pCR rates after neoadjuvant chemotherapy (p = 6.40e-03) and SIRT3 expression was significantly lower in the pCR group than in the non-pCR group in TNBC (p = 4.2e-03). GSEA indicated that SIRT3 was involved in drug-related pathways such as oxidative phosphorylation, metabolism of xenobiotics by cytochrome P450, and drug metabolism.<br/><strong>Conclusion:</strong> Our study suggests that SIRT3 is a potential biomarker for both OS and neoadjuvant chemosensitivity in TNBC. It may also assist in selecting suitable candidates and treatment options for TNBC patients.<br/><br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140076513","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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