Pub Date : 2024-06-26DOI: 10.1007/s00432-024-05814-2
Melda Yeghaian, Teresa M Tareco Bucho, Melissa de Bruin, Alexander Schmitz, Zuhir Bodalal, Egbert F Smit, Regina G H Beets-Tan, Daan van den Broek, Stefano Trebeschi
Purpose: In this study, we aimed to evaluate the potential of routine blood markers, serum tumour markers and their combination in predicting RECIST-defined progression in patients with stage IV non-small cell lung cancer (NSCLC) undergoing treatment with immune checkpoint inhibitors.
Methods: We employed time-varying statistical models and machine learning classifiers in a Monte Carlo cross-validation approach to investigate the association between RECIST-defined progression and blood markers, serum tumour markers and their combination, in a retrospective cohort of 164 patients with NSCLC.
Results: The performance of the routine blood markers in the prediction of progression free survival was moderate. Serum tumour markers and their combination with routine blood markers generally improved performance compared to routine blood markers alone. Elevated levels of C-reactive protein (CRP) and alkaline phosphatase (ALP) ranked as the top predictive routine blood markers, and CYFRA 21.1 was consistently among the most predictive serum tumour markers. Using these classifiers to predict overall survival yielded moderate to high performance, even when cases of death-defined progression were excluded. Performance varied across the treatment journey.
Conclusion: Routine blood tests, especially when combined with serum tumour markers, show moderate predictive value of RECIST-defined progression in NSCLC patients receiving immune checkpoint inhibitors. The relationship between overall survival and RECIST-defined progression may be influenced by confounding factors.
{"title":"Can blood-based markers predict RECIST progression in non-small cell lung cancer treated with immunotherapy?","authors":"Melda Yeghaian, Teresa M Tareco Bucho, Melissa de Bruin, Alexander Schmitz, Zuhir Bodalal, Egbert F Smit, Regina G H Beets-Tan, Daan van den Broek, Stefano Trebeschi","doi":"10.1007/s00432-024-05814-2","DOIUrl":"10.1007/s00432-024-05814-2","url":null,"abstract":"<p><strong>Purpose: </strong>In this study, we aimed to evaluate the potential of routine blood markers, serum tumour markers and their combination in predicting RECIST-defined progression in patients with stage IV non-small cell lung cancer (NSCLC) undergoing treatment with immune checkpoint inhibitors.</p><p><strong>Methods: </strong>We employed time-varying statistical models and machine learning classifiers in a Monte Carlo cross-validation approach to investigate the association between RECIST-defined progression and blood markers, serum tumour markers and their combination, in a retrospective cohort of 164 patients with NSCLC.</p><p><strong>Results: </strong>The performance of the routine blood markers in the prediction of progression free survival was moderate. Serum tumour markers and their combination with routine blood markers generally improved performance compared to routine blood markers alone. Elevated levels of C-reactive protein (CRP) and alkaline phosphatase (ALP) ranked as the top predictive routine blood markers, and CYFRA 21.1 was consistently among the most predictive serum tumour markers. Using these classifiers to predict overall survival yielded moderate to high performance, even when cases of death-defined progression were excluded. Performance varied across the treatment journey.</p><p><strong>Conclusion: </strong>Routine blood tests, especially when combined with serum tumour markers, show moderate predictive value of RECIST-defined progression in NSCLC patients receiving immune checkpoint inhibitors. The relationship between overall survival and RECIST-defined progression may be influenced by confounding factors.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: Tumor-associated macrophages (TAMs) play a critical role in hepatocellular carcinoma (HCC) progression and metastasis. Systematic investigation of the cross-talk between TAMs and HCC may help in searching for the critical target to guard against HCC metastasis.
Methods and results: Herein, we found that TREM1 highly expressed in HCC tissue by analyzing the data obtain from GEO database. Interestingly, the results indicated that TREM1 was primarily expressed by monocytes. Immune infiltration studies further validated that TREM1 expression was positively related with increased infiltration of macrophages in HCC tissues. In vitro, we observed that TREM1 knockdown significantly abrogated the effect of TAMs in promoting the metastasis and epithelial-mesenchymal transition (EMT) of HCC cells. Additionally, cytokine array detection identified CCL7 as the main responsive cytokine following with TREM1 knockdown in TAMs.
Conclusion: Taken together, our findings strongly suggested that high expression of TREM1 was positively associated with metastasis and poor prognosis of HCC. Furthermore, TAMs expressing TREM1 contribute to EMT-based metastasis through secreting CCL7. These results provide a novel insight into the potential development of targeting the TREM1/CCL7 pathway for preventing metastatic HCC.
{"title":"TREM1<sup>+</sup> tumor-associated macrophages secrete CCL7 to promote hepatocellular carcinoma metastasis.","authors":"Simin Huang, Longguang He, Yufei Zhao, Yuxuan Wei, Qiwen Wang, Yi Gao, Xiaofeng Jiang","doi":"10.1007/s00432-024-05831-1","DOIUrl":"10.1007/s00432-024-05831-1","url":null,"abstract":"<p><strong>Purpose: </strong>Tumor-associated macrophages (TAMs) play a critical role in hepatocellular carcinoma (HCC) progression and metastasis. Systematic investigation of the cross-talk between TAMs and HCC may help in searching for the critical target to guard against HCC metastasis.</p><p><strong>Methods and results: </strong>Herein, we found that TREM1 highly expressed in HCC tissue by analyzing the data obtain from GEO database. Interestingly, the results indicated that TREM1 was primarily expressed by monocytes. Immune infiltration studies further validated that TREM1 expression was positively related with increased infiltration of macrophages in HCC tissues. In vitro, we observed that TREM1 knockdown significantly abrogated the effect of TAMs in promoting the metastasis and epithelial-mesenchymal transition (EMT) of HCC cells. Additionally, cytokine array detection identified CCL7 as the main responsive cytokine following with TREM1 knockdown in TAMs.</p><p><strong>Conclusion: </strong>Taken together, our findings strongly suggested that high expression of TREM1 was positively associated with metastasis and poor prognosis of HCC. Furthermore, TAMs expressing TREM1 contribute to EMT-based metastasis through secreting CCL7. These results provide a novel insight into the potential development of targeting the TREM1/CCL7 pathway for preventing metastatic HCC.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11196310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: Hepatocellular carcinoma (HCC) is a critical global health concern, with existing treatments benefiting only a minority of patients. Recent findings implicate the chemokine ligand 17 (CCL17) and its receptor CCR4 as pivotal players in the tumor microenvironment (TME) of various cancers. This investigation aims to delineate the roles of CCL17 and CCR4 in modulating the tumor's immune landscape, assessing their potential as therapeutic interventions and prognostic markers in HCC.
Methods: 873 HCC patients post-radical surgery from 2008 to 2012 at Zhongshan Hospital, Fudan University were retrospectively examined. These individuals were stratified into a training cohort (n = 354) and a validation cohort (n = 519). Through immunohistochemical analysis on HCC tissue arrays, the expressions of CCL17, CCR4, CD73, CD47, HHLA2, and PD-L1 were quantified. Survival metrics were analyzed using the Cox model, and a prognostic nomogram was devised via R software.
Results: The investigation confirmed the presence of CCL17 and CCR4 within the cancerous and stromal compartments of HCC tissues, associating their heightened expression with adverse clinical markers and survival outcomes. Notably, the interplay between CD73 and CCR4 expression in tumor stroma highlighted a novel cellular entity, CCR4 + CD73 + stromal cells, impacting overall and relapse-free survival. A prognostic nomogram amalgamating these immunological markers and clinical variables was established, offering refined prognostic insights and aiding in the management of HCC. The findings suggest that reduced CCR4 and CCR4 + CD73 + cell prevalence may forecast improved outcomes post-TACE.
Conclusion: This comprehensive evaluation of CCR4, CCL17, and associated markers introduces a nuanced understanding of the HCC immunological milieu, proposing CCR4 + CD73 + stromal cells as critical to HCC pathogenesis and patient stratification.
{"title":"Enhancing hepatocellular carcinoma management: prognostic value of integrated CCL17, CCR4, CD73, and HHLA2 expression analysis.","authors":"Wei Gan, Bao-Ye Sun, Zhang-Fu Yang, Cheng Ye, Zhu-Tao Wang, Cheng Zhou, Guo-Qiang Sun, Yong Yi, Shuang-Jian Qiu","doi":"10.1007/s00432-024-05832-0","DOIUrl":"10.1007/s00432-024-05832-0","url":null,"abstract":"<p><strong>Purpose: </strong>Hepatocellular carcinoma (HCC) is a critical global health concern, with existing treatments benefiting only a minority of patients. Recent findings implicate the chemokine ligand 17 (CCL17) and its receptor CCR4 as pivotal players in the tumor microenvironment (TME) of various cancers. This investigation aims to delineate the roles of CCL17 and CCR4 in modulating the tumor's immune landscape, assessing their potential as therapeutic interventions and prognostic markers in HCC.</p><p><strong>Methods: </strong>873 HCC patients post-radical surgery from 2008 to 2012 at Zhongshan Hospital, Fudan University were retrospectively examined. These individuals were stratified into a training cohort (n = 354) and a validation cohort (n = 519). Through immunohistochemical analysis on HCC tissue arrays, the expressions of CCL17, CCR4, CD73, CD47, HHLA2, and PD-L1 were quantified. Survival metrics were analyzed using the Cox model, and a prognostic nomogram was devised via R software.</p><p><strong>Results: </strong>The investigation confirmed the presence of CCL17 and CCR4 within the cancerous and stromal compartments of HCC tissues, associating their heightened expression with adverse clinical markers and survival outcomes. Notably, the interplay between CD73 and CCR4 expression in tumor stroma highlighted a novel cellular entity, CCR4 + CD73 + stromal cells, impacting overall and relapse-free survival. A prognostic nomogram amalgamating these immunological markers and clinical variables was established, offering refined prognostic insights and aiding in the management of HCC. The findings suggest that reduced CCR4 and CCR4 + CD73 + cell prevalence may forecast improved outcomes post-TACE.</p><p><strong>Conclusion: </strong>This comprehensive evaluation of CCR4, CCL17, and associated markers introduces a nuanced understanding of the HCC immunological milieu, proposing CCR4 + CD73 + stromal cells as critical to HCC pathogenesis and patient stratification.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11196339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: Circular RNAs (circRNAs) are increasingly recognized for their important roles in various cancers, including papillary thyroid cancer (PTC). The specific mechanisms by which the circLIF receptor subunit alpha (circLIFR, hsa_circ_0072309) influences PTC progression remain largely unknown.
Methods: In our study, CircLIFR, miR-429, and TIMP2 levels were assessed using reverse transcription-quantitative PCR. The roles of circLIFR and miR-429 in PTC cells were determined using Cell Counting Kit-8, colony formation, wound healing, and Transwell assays. Western blotting was utilized to examine the levels of TIMP2. The direct interaction between circLIFR, TIMP2, and miR-429 was confirmed using dual-luciferase reporter, RNA immunoprecipitation, and fluorescence in situ hybridization assays.
Results: In PTC tissues and cells, a decrease in circLIFR and TIMP2 levels, accompanied by an increase in miR-429 levels, was observed. Overexpression of circLIFR or downregulation of miR-429 effectively suppressed the proliferation and migration of PTC cells. Conversely, the knockdown of circLIFR or overexpression of miR-429 had the opposite effect. Furthermore, circLIFR overexpression suppressed tumor growth in vivo. Mechanistically, circLIFR modulated TIMP2 expression by serving as a sponge for miR-429. Rescue experiments indicated that the antitumor effect of circLIFR could be reversed by miR-429.
Conclusion: This study confirmed circLIFR as a novel tumor suppressor delayed PTC progression through the miR-429/TIMP2 axis. These findings suggested that circLIFR held promise as a potential therapeutic target for PTC.
{"title":"Circular RNA circLIFR suppresses papillary thyroid cancer progression by modulating the miR-429/TIMP2 axis.","authors":"Fengyuan Zhang, Jiazheng Li, Jingjing Xu, Xugan Jiang, Shengxia Chen, Qais Ahmad Nasser","doi":"10.1007/s00432-024-05839-7","DOIUrl":"10.1007/s00432-024-05839-7","url":null,"abstract":"<p><strong>Purpose: </strong>Circular RNAs (circRNAs) are increasingly recognized for their important roles in various cancers, including papillary thyroid cancer (PTC). The specific mechanisms by which the circLIF receptor subunit alpha (circLIFR, hsa_circ_0072309) influences PTC progression remain largely unknown.</p><p><strong>Methods: </strong>In our study, CircLIFR, miR-429, and TIMP2 levels were assessed using reverse transcription-quantitative PCR. The roles of circLIFR and miR-429 in PTC cells were determined using Cell Counting Kit-8, colony formation, wound healing, and Transwell assays. Western blotting was utilized to examine the levels of TIMP2. The direct interaction between circLIFR, TIMP2, and miR-429 was confirmed using dual-luciferase reporter, RNA immunoprecipitation, and fluorescence in situ hybridization assays.</p><p><strong>Results: </strong>In PTC tissues and cells, a decrease in circLIFR and TIMP2 levels, accompanied by an increase in miR-429 levels, was observed. Overexpression of circLIFR or downregulation of miR-429 effectively suppressed the proliferation and migration of PTC cells. Conversely, the knockdown of circLIFR or overexpression of miR-429 had the opposite effect. Furthermore, circLIFR overexpression suppressed tumor growth in vivo. Mechanistically, circLIFR modulated TIMP2 expression by serving as a sponge for miR-429. Rescue experiments indicated that the antitumor effect of circLIFR could be reversed by miR-429.</p><p><strong>Conclusion: </strong>This study confirmed circLIFR as a novel tumor suppressor delayed PTC progression through the miR-429/TIMP2 axis. These findings suggested that circLIFR held promise as a potential therapeutic target for PTC.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11196293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-25DOI: 10.1007/s00432-024-05845-9
Jiannan Xu, Songyao Chen, Tengfei Hao, Guangyao Liu, Kai Zhang, Changhua Zhang, Yulong He
Background: Mex-3 RNA binding family members are well-established to be important in cancer development and progression. However, the functions of Mex-3 RNA binding family member A (MEX3A) in colorectal cancer (CRC) metastasis remain poorly understood. In this study, we aim to reveal the function and the mechanism of MEX3A in promoting CRC metastasis.
Methods: We used multiple databases including TCGA database, UALCAN, LinkedOmics, CancerSEA, GeneMANIA and STRING database to investigate the expression, the functions and underlying molecular mechanism of MEX3A in CRC. Multiple experimental methods were adapted to determine the study, including real-time PCR (qPCR), immunohistochemistry (IHC), western blot (WB), transfection, transwell migration and invasion assays, immunofluorescence (IF).
Results: We found that MEX3A was significantly upregulated and correlated to tumor stage and lymph nodal metastasis in CRC through bioinformatics analysis and tissue immunohistochemistry (IHC). The higher expression of MEX3A in CRC correlated with poor recurrence-free survival (RFS) and overall survival (OS). In vitro studies showed that knockdown of MEX3A suppressed EMT transition, invasion and metastasis of CRC cells. Mechanistically, we revealed that MEX3A promotes epithelial-mesenchymal transition (EMT), invasion and metastasis of CRC cells by upregulating the Wnt/β-catenin signaling pathway.
Conclusion: In conclusion, our study reveals that MEX3A promotes CRC migration, invasion and EMT via regulating the Wnt/β-catenin signaling pathway and could be a novel therapeutic target for this patient population.
{"title":"MEX3A promotes colorectal cancer migration, invasion and EMT via regulating the Wnt/β-catenin signaling pathway.","authors":"Jiannan Xu, Songyao Chen, Tengfei Hao, Guangyao Liu, Kai Zhang, Changhua Zhang, Yulong He","doi":"10.1007/s00432-024-05845-9","DOIUrl":"10.1007/s00432-024-05845-9","url":null,"abstract":"<p><strong>Background: </strong>Mex-3 RNA binding family members are well-established to be important in cancer development and progression. However, the functions of Mex-3 RNA binding family member A (MEX3A) in colorectal cancer (CRC) metastasis remain poorly understood. In this study, we aim to reveal the function and the mechanism of MEX3A in promoting CRC metastasis.</p><p><strong>Methods: </strong>We used multiple databases including TCGA database, UALCAN, LinkedOmics, CancerSEA, GeneMANIA and STRING database to investigate the expression, the functions and underlying molecular mechanism of MEX3A in CRC. Multiple experimental methods were adapted to determine the study, including real-time PCR (qPCR), immunohistochemistry (IHC), western blot (WB), transfection, transwell migration and invasion assays, immunofluorescence (IF).</p><p><strong>Results: </strong>We found that MEX3A was significantly upregulated and correlated to tumor stage and lymph nodal metastasis in CRC through bioinformatics analysis and tissue immunohistochemistry (IHC). The higher expression of MEX3A in CRC correlated with poor recurrence-free survival (RFS) and overall survival (OS). In vitro studies showed that knockdown of MEX3A suppressed EMT transition, invasion and metastasis of CRC cells. Mechanistically, we revealed that MEX3A promotes epithelial-mesenchymal transition (EMT), invasion and metastasis of CRC cells by upregulating the Wnt/β-catenin signaling pathway.</p><p><strong>Conclusion: </strong>In conclusion, our study reveals that MEX3A promotes CRC migration, invasion and EMT via regulating the Wnt/β-catenin signaling pathway and could be a novel therapeutic target for this patient population.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11196291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-25DOI: 10.1007/s00432-024-05840-0
Jun Luo, Zheng Yao, Weiren Liang, Danjun Song, Hui Zeng, Yi Jiang, Zhehan Bao, Jiaping Zheng, Yinan Ding
Objectives: Cholangiocarcinoma (CCA) is a rare tumor with a poor prognosis and poses significant therapeutic challenges. Herein, we investigated the mechanism of efficacy of 125I seed implantation therapy in CCA, focusing on the induction of reactive oxygen species (ROS)-mediated apoptosis and the involvement of glutathione peroxidase 2 (GPX2).
Materials and methods: Human cholangiocarcinoma cell lines QBC939 and RBE were purchased for in vitro studies. In vivo studies were performed using a rabbit VX2 CCA model. Apoptosis and proliferation were detected by TUNEL staining and clone formation, respectively. ROS generation was detected by dihydroethidium staining. Histological evaluation was performed by hematoxylin and eosin staining. Protein expression was determined by Western blotting and immunohistochemistry.
Results: Our results demonstrate that 125I seeds effectively inhibited tumor growth in the rabbit VX2 tumor model and promoted the apoptosis of CCA cells in vitro in a dose-dependent manner. Molecular analyses indicate a marked increase in reactive oxygen species (ROS) levels following treatment with 125I seeds, suggesting the involvement of ROS-mediated apoptosis in the therapeutic mechanism. Furthermore, the downregulation of glutathione peroxidase 2 (GPX2) was observed, indicating its potential role in modulating ROS-mediated apoptosis in CCA.
Conclusion: 125I seed implantation therapy exerts therapeutic effects on CCA by inducing ROS-mediated apoptosis. The downregulation of GPX2 may contribute to enhanced ROS accumulation and apoptotic cell death. These findings provide mechanistic insights into the therapeutic potential of 125I seed implantation for CCA and highlight ROS-mediated apoptosis and GPX2 regulation as promising targets for further investigation and therapeutic intervention in this malignancy.
目的:胆管癌(CCA)是一种罕见的肿瘤,预后较差,给治疗带来了巨大挑战。在此,我们研究了 125I 种子植入疗法在 CCA 中的疗效机制,重点是诱导活性氧(ROS)介导的细胞凋亡以及谷胱甘肽过氧化物酶 2(GPX2)的参与。使用兔 VX2 CCA 模型进行体内研究。凋亡和增殖分别通过 TUNEL 染色和克隆形成进行检测。通过二氢乙锭染色检测 ROS 的生成。组织学评估采用苏木精和伊红染色法。蛋白质表达通过 Western 印迹法和免疫组化法测定:结果:我们的研究结果表明,125I种子能有效抑制兔VX2肿瘤模型中的肿瘤生长,并以剂量依赖的方式促进体外CCA细胞的凋亡。分子分析表明,使用 125I 种子治疗后,活性氧(ROS)水平明显升高,表明 ROS 介导的细胞凋亡参与了治疗机制。结论:125I 种子植入疗法通过诱导 ROS 介导的细胞凋亡对 CCA 发挥治疗作用。GPX2 的下调可能导致 ROS 积累和细胞凋亡的增强。这些发现从机理上揭示了125I粒子植入对CCA的治疗潜力,并强调了ROS介导的细胞凋亡和GPX2调控是对这种恶性肿瘤进行进一步研究和治疗干预的有希望的靶点。
{"title":"Mechanistic insights into <sup>125</sup>I seed implantation therapy for Cholangiocarcinoma: focus on ROS-Mediated apoptosis and the role of GPX2.","authors":"Jun Luo, Zheng Yao, Weiren Liang, Danjun Song, Hui Zeng, Yi Jiang, Zhehan Bao, Jiaping Zheng, Yinan Ding","doi":"10.1007/s00432-024-05840-0","DOIUrl":"10.1007/s00432-024-05840-0","url":null,"abstract":"<p><strong>Objectives: </strong>Cholangiocarcinoma (CCA) is a rare tumor with a poor prognosis and poses significant therapeutic challenges. Herein, we investigated the mechanism of efficacy of <sup>125</sup>I seed implantation therapy in CCA, focusing on the induction of reactive oxygen species (ROS)-mediated apoptosis and the involvement of glutathione peroxidase 2 (GPX2).</p><p><strong>Materials and methods: </strong>Human cholangiocarcinoma cell lines QBC939 and RBE were purchased for in vitro studies. In vivo studies were performed using a rabbit VX2 CCA model. Apoptosis and proliferation were detected by TUNEL staining and clone formation, respectively. ROS generation was detected by dihydroethidium staining. Histological evaluation was performed by hematoxylin and eosin staining. Protein expression was determined by Western blotting and immunohistochemistry.</p><p><strong>Results: </strong>Our results demonstrate that <sup>125</sup>I seeds effectively inhibited tumor growth in the rabbit VX2 tumor model and promoted the apoptosis of CCA cells in vitro in a dose-dependent manner. Molecular analyses indicate a marked increase in reactive oxygen species (ROS) levels following treatment with <sup>125</sup>I seeds, suggesting the involvement of ROS-mediated apoptosis in the therapeutic mechanism. Furthermore, the downregulation of glutathione peroxidase 2 (GPX2) was observed, indicating its potential role in modulating ROS-mediated apoptosis in CCA.</p><p><strong>Conclusion: </strong><sup>125</sup>I seed implantation therapy exerts therapeutic effects on CCA by inducing ROS-mediated apoptosis. The downregulation of GPX2 may contribute to enhanced ROS accumulation and apoptotic cell death. These findings provide mechanistic insights into the therapeutic potential of <sup>125</sup>I seed implantation for CCA and highlight ROS-mediated apoptosis and GPX2 regulation as promising targets for further investigation and therapeutic intervention in this malignancy.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11196350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: Limited data are available regarding the partner and localizer of BRCA2 (PALB2) in Chinese patients with early breast cancer. This study aimed to assess the spectrum and characteristics of germline PALB2 pathogenic variants in this population.
Methods: Peripheral blood samples were collected from 1556 patients diagnosed with BRCA1/2-negative early-onset breast cancer. All coding regions and exon‒intron boundaries of the PALB2 genes were screened through next-generation sequencing.
Results: The prevalence of PALB2 pathogenic variants was approximately 0.77% in the cohort. Eleven PALB2 pathogenic variants were identified in twelve participants, including five frameshift mutations and six nonsense mutations. All other variants were detected once, except for PALB2 c.1056_1057del (detected twice). Two PALB2 carriers (2/12, 16.7%) have documented family history of breast cancer and/or ovarian cancer. Patients with a positive family history exhibited a threefold higher possibility of being identified as PALB2 carriers than those without a family history (2% vs. 0.69%), although the difference was not statistically significant (p = 0.178). Compared to non-carriers, PALB2 carriers has a tendency to appear in younger age (≤ 30 years) (25% vs 14.4%), human epidermal growth factor receptor-2 (HER2)-negative status (83.3% vs. 70.2%), and diagnosed with invasive micropapillary carcinoma (16.7% vs 3.1%).
Conclusion: The prevalence of the germline PALB2 pathogenic variants was approximately 0.77% in Chinese patients with BRCA1/2-negative early-onset breast cancer. Our findings is crucial for understanding population-specific genetic risks and offering insights that can enhance genetic counseling and genetic testing strategies in this population.
目的:有关中国早期乳腺癌患者中BRCA2(PALB2)的伴侣和定位者的数据有限。本研究旨在评估该人群中 PALB2 种系致病变异的谱系和特征:方法:收集了 1556 例 BRCA1/2 阴性早发乳腺癌患者的外周血样本。通过新一代测序筛选了 PALB2 基因的所有编码区和外显子内含子边界:结果:队列中PALB2致病变异的发生率约为0.77%。在12名参与者中发现了11个PALB2致病变异,包括5个框移突变和6个无义突变。除PALB2 c.1056_1057del(检测到两次)外,其他变异均检测到一次。两名 PALB2 基因携带者(2/12,16.7%)有乳腺癌和/或卵巢癌家族史记录。有阳性家族史的患者被鉴定为PALB2携带者的可能性是无家族史患者的三倍(2% vs. 0.69%),但差异无统计学意义(p = 0.178)。与非携带者相比,PALB2携带者的年龄更小(小于30岁)(25% vs 14.4%),人表皮生长因子受体-2(HER2)阴性(83.3% vs 70.2%),诊断为浸润性微乳头状癌(16.7% vs 3.1%):结论:在BRCA1/2阴性的中国早发乳腺癌患者中,PALB2种系致病变体的患病率约为0.77%。我们的研究结果对于了解特定人群的遗传风险至关重要,并为加强该人群的遗传咨询和基因检测策略提供了启示。
{"title":"Spectrum and characteristics of germline PALB2 pathogenic variants in 1556 early-onset breast cancer patients in China.","authors":"Jing Li, Peng He, Qindong Cai, Lili Chen, Yali Wang, Weifeng Cai, Yibin Qiu, Shunyi Liu, Wenhui Guo, Minyan Chen, Yuxiang Lin, Chuan Wang, Fangmeng Fu","doi":"10.1007/s00432-024-05758-7","DOIUrl":"10.1007/s00432-024-05758-7","url":null,"abstract":"<p><strong>Purpose: </strong>Limited data are available regarding the partner and localizer of BRCA2 (PALB2) in Chinese patients with early breast cancer. This study aimed to assess the spectrum and characteristics of germline PALB2 pathogenic variants in this population.</p><p><strong>Methods: </strong>Peripheral blood samples were collected from 1556 patients diagnosed with BRCA1/2-negative early-onset breast cancer. All coding regions and exon‒intron boundaries of the PALB2 genes were screened through next-generation sequencing.</p><p><strong>Results: </strong>The prevalence of PALB2 pathogenic variants was approximately 0.77% in the cohort. Eleven PALB2 pathogenic variants were identified in twelve participants, including five frameshift mutations and six nonsense mutations. All other variants were detected once, except for PALB2 c.1056_1057del (detected twice). Two PALB2 carriers (2/12, 16.7%) have documented family history of breast cancer and/or ovarian cancer. Patients with a positive family history exhibited a threefold higher possibility of being identified as PALB2 carriers than those without a family history (2% vs. 0.69%), although the difference was not statistically significant (p = 0.178). Compared to non-carriers, PALB2 carriers has a tendency to appear in younger age (≤ 30 years) (25% vs 14.4%), human epidermal growth factor receptor-2 (HER2)-negative status (83.3% vs. 70.2%), and diagnosed with invasive micropapillary carcinoma (16.7% vs 3.1%).</p><p><strong>Conclusion: </strong>The prevalence of the germline PALB2 pathogenic variants was approximately 0.77% in Chinese patients with BRCA1/2-negative early-onset breast cancer. Our findings is crucial for understanding population-specific genetic risks and offering insights that can enhance genetic counseling and genetic testing strategies in this population.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11196361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-25DOI: 10.1007/s00432-024-05825-z
Yuan Liu, Shan-Shan Fang, Run-Sheng Zhao, Bo Liu, Yi-Qiang Jin, Quan Li
Purpose: This study aimed to assess the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus platinum versus paclitaxel plus platinum as first-line therapy in patients with metastatic or recurrent cervical cancer.
Methods: Between October 2020 and March 2022, consecutive patients with diagnosed with metastatic or recurrent cervical cancer were retrospectively recruited in our hospital. Fifty-four patients were treated with nab-paclitaxel plus cisplatin or carboplatin. Twenty-four patients were treated with paclitaxel plus cisplatin or carboplatin. A propensity score matching (PSM) analysis was done using a multivariable logistic regression model. The two groups were compared for objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in the raw and matched dataset.
Results: The nab-paclitaxel group showed a higher ORR than the paclitaxel group both in the raw dataset (72.2% vs. 45.8%; P = 0.025) and matched dataset (81.1% vs. 47.6%; P = 0.008). The median PFS was significantly longer in the nab-paclitaxel group than in the paclitaxel group both in the raw and matched dataset (12 vs. 7 months; P < 0.05). The median OS was not reached in the nab-paclitaxel group compared with 15 months in the paclitaxel group, with a trend toward prolongation. The most common toxicity was hematological adverse events, including grade 3-4 neutropenia, grade 3 anemia and thrombocytopenia in both groups and no statistical differences were observed between the groups (all P > 0.05).
Conclusion: Compared with paclitaxel plus platinum, nab-paclitaxel plus platinum may be an effective and tolerable option as first-line therapy for patients with metastatic or recurrent cervical cancer.
目的:本研究旨在评估纳米颗粒白蛋白结合紫杉醇(nab-紫杉醇)加铂与紫杉醇加铂作为转移性或复发性宫颈癌患者一线治疗的有效性和安全性:2020年10月至2022年3月期间,回顾性招募本院连续确诊的转移性或复发性宫颈癌患者。54名患者接受了纳布-紫杉醇加顺铂或卡铂治疗。24名患者接受了紫杉醇加顺铂或卡铂治疗。使用多变量逻辑回归模型进行了倾向得分匹配(PSM)分析。比较了原始数据集和匹配数据集中两组患者的客观反应率(ORR)、无进展生存期(PFS)和总生存期(OS):结果:在原始数据集(72.2% vs. 45.8%;P = 0.025)和匹配数据集(81.1% vs. 47.6%;P = 0.008)中,纳布-紫杉醇组的客观反应率均高于紫杉醇组。在原始数据集和匹配数据集中,纳布-紫杉醇组的中位生存期明显长于紫杉醇组(12个月 vs. 7个月;P 0.05):结论:与紫杉醇加铂相比,纳布-紫杉醇加铂可能是转移性或复发性宫颈癌患者一线治疗的有效且可耐受的选择。
{"title":"Nab-paclitaxel plus platinum versus paclitaxel plus platinum as first-line therapy in patients with metastatic or recurrent cervical cancer.","authors":"Yuan Liu, Shan-Shan Fang, Run-Sheng Zhao, Bo Liu, Yi-Qiang Jin, Quan Li","doi":"10.1007/s00432-024-05825-z","DOIUrl":"10.1007/s00432-024-05825-z","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to assess the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus platinum versus paclitaxel plus platinum as first-line therapy in patients with metastatic or recurrent cervical cancer.</p><p><strong>Methods: </strong>Between October 2020 and March 2022, consecutive patients with diagnosed with metastatic or recurrent cervical cancer were retrospectively recruited in our hospital. Fifty-four patients were treated with nab-paclitaxel plus cisplatin or carboplatin. Twenty-four patients were treated with paclitaxel plus cisplatin or carboplatin. A propensity score matching (PSM) analysis was done using a multivariable logistic regression model. The two groups were compared for objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in the raw and matched dataset.</p><p><strong>Results: </strong>The nab-paclitaxel group showed a higher ORR than the paclitaxel group both in the raw dataset (72.2% vs. 45.8%; P = 0.025) and matched dataset (81.1% vs. 47.6%; P = 0.008). The median PFS was significantly longer in the nab-paclitaxel group than in the paclitaxel group both in the raw and matched dataset (12 vs. 7 months; P < 0.05). The median OS was not reached in the nab-paclitaxel group compared with 15 months in the paclitaxel group, with a trend toward prolongation. The most common toxicity was hematological adverse events, including grade 3-4 neutropenia, grade 3 anemia and thrombocytopenia in both groups and no statistical differences were observed between the groups (all P > 0.05).</p><p><strong>Conclusion: </strong>Compared with paclitaxel plus platinum, nab-paclitaxel plus platinum may be an effective and tolerable option as first-line therapy for patients with metastatic or recurrent cervical cancer.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11196321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-25DOI: 10.1007/s00432-024-05835-x
Siyer Roohani, Titus Rotermund, Felix Ehret, Tomasz Dziodzio, Armin Jarosch, Frederik Maximilian Schäfer, Anne Flörcken, Silvan Wittenberg, Daniel Zips, David Kaul
Purpose: This study sought to investigate oncological outcomes and prognostic factors for patients with angiosarcomas (AS).
Methods: This single-center, retrospective cohort study, analyzed histopathologically confirmed AS cases. Primarily diagnosed, locally recurrent and metastatic AS were included. Overall survival (OS), local control (LC) and local progression-free survival (LPFS) were assessed by Kaplan-Meier estimator. Multivariable Cox regression analysis was performed to detect factors associated with OS and LPFS.
Results: In total, 118 patients with a median follow-up of 6.6 months were included. The majority presented with localized disease (62.7%), followed by metastatic (31.4%) and locally recurrent (5.9%) disease. Seventy-four patients (62.7%) received surgery, of which 29 (39.2%) were treated with surgery only, 38 (51.4%) with surgery and perioperative radiotherapy or chemotherapy, and 7 (9.4%) with surgery, perioperative radiotherapy and chemotherapy. Multivariable Cox regression of OS showed a significant association with age per year (hazard ratio (HR): 1.03, p = 0.044) and metastatic disease at presentation (hazard ratio: 3.24, p = 0.015). For LPFS, age per year (HR: 1.04, p = 0.008), locally recurrent disease at presentation (HR: 5.32, p = 0.013), and metastatic disease at presentation (HR: 4.06, p = 0.009) had significant associations. Tumor size, epithelioid components, margin status, and perioperative RT and/or CTX were not significantly associated with OS or LPFS.
Conclusion: Older age and metastatic disease at initial presentation status were negatively associated with OS and LPFS. Innovative and collaborative effort is warranted to overcome the epidemiologic challenges of AS by collecting multi-institutional datasets, characterizing AS molecularly and identifying new perioperative therapies to improve patient outcomes.
{"title":"Angiosarcoma: clinical outcomes and prognostic factors, a single-center analysis.","authors":"Siyer Roohani, Titus Rotermund, Felix Ehret, Tomasz Dziodzio, Armin Jarosch, Frederik Maximilian Schäfer, Anne Flörcken, Silvan Wittenberg, Daniel Zips, David Kaul","doi":"10.1007/s00432-024-05835-x","DOIUrl":"10.1007/s00432-024-05835-x","url":null,"abstract":"<p><strong>Purpose: </strong>This study sought to investigate oncological outcomes and prognostic factors for patients with angiosarcomas (AS).</p><p><strong>Methods: </strong>This single-center, retrospective cohort study, analyzed histopathologically confirmed AS cases. Primarily diagnosed, locally recurrent and metastatic AS were included. Overall survival (OS), local control (LC) and local progression-free survival (LPFS) were assessed by Kaplan-Meier estimator. Multivariable Cox regression analysis was performed to detect factors associated with OS and LPFS.</p><p><strong>Results: </strong>In total, 118 patients with a median follow-up of 6.6 months were included. The majority presented with localized disease (62.7%), followed by metastatic (31.4%) and locally recurrent (5.9%) disease. Seventy-four patients (62.7%) received surgery, of which 29 (39.2%) were treated with surgery only, 38 (51.4%) with surgery and perioperative radiotherapy or chemotherapy, and 7 (9.4%) with surgery, perioperative radiotherapy and chemotherapy. Multivariable Cox regression of OS showed a significant association with age per year (hazard ratio (HR): 1.03, p = 0.044) and metastatic disease at presentation (hazard ratio: 3.24, p = 0.015). For LPFS, age per year (HR: 1.04, p = 0.008), locally recurrent disease at presentation (HR: 5.32, p = 0.013), and metastatic disease at presentation (HR: 4.06, p = 0.009) had significant associations. Tumor size, epithelioid components, margin status, and perioperative RT and/or CTX were not significantly associated with OS or LPFS.</p><p><strong>Conclusion: </strong>Older age and metastatic disease at initial presentation status were negatively associated with OS and LPFS. Innovative and collaborative effort is warranted to overcome the epidemiologic challenges of AS by collecting multi-institutional datasets, characterizing AS molecularly and identifying new perioperative therapies to improve patient outcomes.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11196347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: Beyond the Thyroid Imaging Reporting and Data System (TIRADS) classification of thyroid nodules, additional factors must be weighed in the decision to perform fine needle aspiration (FNA). In this study, we aimed to identify risk factors for malignancy in patients with ultrasound-classified Chinese-TIRADS (C-TIRADS) 4 A nodules.
Methods: Patients who underwent thyroid FNA at our institution between May 2021 and September 2022 were enrolled. We collected demographic data, including age, sex, previous radiation exposure, and family history. An in-person questionnaire was used to collect lifestyle data, such as smoking habits and alcohol consumption. Body mass index (BMI) was calculated. The serum levels of thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) were measured. Prior to FNA, ultrasonic inspection reports were reviewed. The cytologic diagnoses for FNA of thyroid nodules followed the Bethesda System for Reporting Thyroid Cytopathology (2017).
Results: Among the 252 C-TIRADS 4 A nodules, 103 were malignant. Compared to those in the benign group, the patients in the malignant group had a younger age (42.2 ± 13.6 vs. 51.5 ± 14.0 years, P < 0.001). Logistic regression showed that advanced age was associated with a lower risk of malignancy in C-TIRADS 4 A nodules (OR = 0.95, 95% CI 0.93 ~ 0.97, P < 0.001). We demonstrated a decreased risk of malignancy in patients with 48.5 years or older.
Conclusion: Advanced age was associated with a decreased risk of malignancy in patients with C-TIRADS 4 A nodules. This study indicated that in addition to sonographic characteristics, patient age should be considered when assessing the risk of malignancy.
目的:除了甲状腺成像报告和数据系统(TIRADS)对甲状腺结节的分类外,在决定是否进行细针穿刺(FNA)时还必须权衡其他因素。在这项研究中,我们旨在确定经超声分类的中国-TIRADS(C-TIRADS)4 A 结节患者发生恶性肿瘤的风险因素:方法:选取2021年5月至2022年9月期间在我院接受甲状腺FNA检查的患者作为研究对象。我们收集了人口统计学数据,包括年龄、性别、既往辐射暴露和家族史。我们还采用当面问卷调查的方式收集生活方式数据,如吸烟习惯和饮酒量。我们还计算了体重指数(BMI)。测量血清中促甲状腺激素(TSH)、甲状腺过氧化物酶抗体(TPOAb)和甲状腺球蛋白抗体(TGAb)的水平。在进行 FNA 之前,对超声波检查报告进行审查。甲状腺结节FNA的细胞学诊断遵循《贝塞斯达甲状腺细胞病理学报告系统(2017)》:在252个C-TIRADS 4 A结节中,103个为恶性。与良性组相比,恶性组患者的年龄较小(42.2±13.6 岁 vs. 51.5±14.0 岁,P 结论:高龄与甲状腺结节的风险降低有关:高龄与 C-TIRADS 4 A 结节患者发生恶性肿瘤的风险降低有关。这项研究表明,在评估恶性肿瘤风险时,除了声像图特征外,还应考虑患者的年龄。
{"title":"Clinical risk factors and cancer risk of thyroid imaging reporting and data system category 4 A thyroid nodules.","authors":"Jing Cheng, Bing Han, Yingchao Chen, Qin Li, Wenwen Xia, Ningjian Wang, Yingli Lu","doi":"10.1007/s00432-024-05847-7","DOIUrl":"10.1007/s00432-024-05847-7","url":null,"abstract":"<p><strong>Purpose: </strong>Beyond the Thyroid Imaging Reporting and Data System (TIRADS) classification of thyroid nodules, additional factors must be weighed in the decision to perform fine needle aspiration (FNA). In this study, we aimed to identify risk factors for malignancy in patients with ultrasound-classified Chinese-TIRADS (C-TIRADS) 4 A nodules.</p><p><strong>Methods: </strong>Patients who underwent thyroid FNA at our institution between May 2021 and September 2022 were enrolled. We collected demographic data, including age, sex, previous radiation exposure, and family history. An in-person questionnaire was used to collect lifestyle data, such as smoking habits and alcohol consumption. Body mass index (BMI) was calculated. The serum levels of thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) were measured. Prior to FNA, ultrasonic inspection reports were reviewed. The cytologic diagnoses for FNA of thyroid nodules followed the Bethesda System for Reporting Thyroid Cytopathology (2017).</p><p><strong>Results: </strong>Among the 252 C-TIRADS 4 A nodules, 103 were malignant. Compared to those in the benign group, the patients in the malignant group had a younger age (42.2 ± 13.6 vs. 51.5 ± 14.0 years, P < 0.001). Logistic regression showed that advanced age was associated with a lower risk of malignancy in C-TIRADS 4 A nodules (OR = 0.95, 95% CI 0.93 ~ 0.97, P < 0.001). We demonstrated a decreased risk of malignancy in patients with 48.5 years or older.</p><p><strong>Conclusion: </strong>Advanced age was associated with a decreased risk of malignancy in patients with C-TIRADS 4 A nodules. This study indicated that in addition to sonographic characteristics, patient age should be considered when assessing the risk of malignancy.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11196368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}