Background: Gastric cancer remains a leading cause of cancer-related death. Early detection is crucial, but effective non-invasive screening methods are lacking. This study investigates the diagnostic potential of salivary Cystatin S (CST4) and MicroRNA-223 (miR-223) biomarkers, integrated with health-related factors for early gastric cancer detection.
Methods: Forty-five patients with gastric cancer and 45 healthy controls participated in this case-control study. Saliva samples were collected and analyzed for CST4 and miR-223 levels. Demographic data and health-related factors, including hot drink consumption, gastric ulcer history, Helicobacter pylori infection, body mass index (BMI), DMFT (Dental Decay, Missing, and Filled Teeth), and salty food intake, were also collected through a standardized questionnaire. Salivary CST4 levels were determined using enzyme-linked immunosorbent assay (ELISA), and miR-223 levels were quantified using real-time polymerase chain reaction (PCR). Statistical analyses, encompassing multiple logistic regression, were conducted to evaluate the diagnostic efficacy of the biomarkers alongside health-related parameters.
Results: Significant differences in salivary CST4 and miR-223 levels were observed between gastric cancer patients and healthy controls (P < 0.001). Combining salivary biomarkers and health-related factors yielded high accuracy, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.89 for the model using CST4 and miR-223. Multiple logistic regression analysis identified several health-related factors, including gastric ulcer history and Helicobacter pylori infection, as significant predictors of gastric cancer risk. The inclusion of health factors, along with biomarkers, enhanced early detection's sensitivity and specificity.
Conclusions: The study highlights the potential of salivary biomarkers CST4 and miR-223 as non-invasive tools for early gastric cancer detection. Integrating these biomarkers with health-related factors, such as gastric ulcer history and Helicobacter pylori infection, enhances the risk assessment and diagnostic accuracy for gastric cancer.
{"title":"Integrating Salivary Biomarkers CST4 and <i>miR-223</i> With Health-Related Factors for Gastric Cancer Detection and Risk Assessment.","authors":"Maryam Koopaie, Saba Manafi, Soheila Manifar, Shima Younespour, Sajad Kolahdooz, Mahdi Karimipour Pareshkooh","doi":"10.1177/11795549251375898","DOIUrl":"10.1177/11795549251375898","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer remains a leading cause of cancer-related death. Early detection is crucial, but effective non-invasive screening methods are lacking. This study investigates the diagnostic potential of salivary Cystatin S (CST4) and <i>MicroRNA-223</i> (<i>miR-223</i>) biomarkers, integrated with health-related factors for early gastric cancer detection.</p><p><strong>Methods: </strong>Forty-five patients with gastric cancer and 45 healthy controls participated in this case-control study. Saliva samples were collected and analyzed for CST4 and <i>miR-223</i> levels. Demographic data and health-related factors, including hot drink consumption, gastric ulcer history, <i>Helicobacter pylori</i> infection, body mass index (BMI), DMFT (Dental Decay, Missing, and Filled Teeth), and salty food intake, were also collected through a standardized questionnaire. Salivary CST4 levels were determined using enzyme-linked immunosorbent assay (ELISA), and <i>miR-223</i> levels were quantified using real-time polymerase chain reaction (PCR). Statistical analyses, encompassing multiple logistic regression, were conducted to evaluate the diagnostic efficacy of the biomarkers alongside health-related parameters.</p><p><strong>Results: </strong>Significant differences in salivary CST4 and <i>miR-223</i> levels were observed between gastric cancer patients and healthy controls (<i>P</i> < 0.001). Combining salivary biomarkers and health-related factors yielded high accuracy, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.89 for the model using CST4 and <i>miR-223</i>. Multiple logistic regression analysis identified several health-related factors, including gastric ulcer history and <i>Helicobacter pylori</i> infection, as significant predictors of gastric cancer risk. The inclusion of health factors, along with biomarkers, enhanced early detection's sensitivity and specificity.</p><p><strong>Conclusions: </strong>The study highlights the potential of salivary biomarkers CST4 and <i>miR-223</i> as non-invasive tools for early gastric cancer detection. Integrating these biomarkers with health-related factors, such as gastric ulcer history and <i>Helicobacter pylori</i> infection, enhances the risk assessment and diagnostic accuracy for gastric cancer.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"19 ","pages":"11795549251375898"},"PeriodicalIF":1.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-12eCollection Date: 2025-01-01DOI: 10.1177/11795549251363829
Yutao Wang, Lu Zhao, Jiahao Zhao, Xuanyu Wei, Daorong Wang, Jun Liu, Linjie Hu, Bing Xu, Jun Ji, Jiayi Zhang, Chaowu Chen, Dong Tang
Background: Accurate intraoperative navigation remains challenging in gastrointestinal tumor surgery. This study aims to explore the potential of optical coherence tomography (OCT) and endoscopic ultrasonography (EUS) in enhancing the accuracy of intraoperative navigation.
Methods: This single-center diagnostic study was conducted at Northern Jiangsu People's Hospital from August to December 2024. This study is part of a prospective study, and more patients will be recruited in the future. The normal tissues, tumor tissues, vascular tissues, adipose tissues and lymph nodes of 12 patients with gastrointestinal tumors were collected for OCT and EUS scanning, and the image differences were compared. In addition, 43 lymph node specimens from 18 randomly selected patients were scanned by OCT and EUS, and pathological reports were used as the baseline. The results of OCT and EUS were compared retrospectively.
Results: There are notable differences between OCT and EUS imaging. EUS can capture images of the entire tissue layer, making it more effective than OCT in assessing tumor invasion depth. Conversely, OCT serves as an "optical biopsy," providing higher precision in the early stages of lesions. Our further research indicates that the combined application of these modalities holds significant potential. In a double-blind evaluation of 43 lymph nodes from 18 randomly selected patients, OCT demonstrated a sensitivity of 81.25%, specificity of 88.89%, and a positive predictive value (PPV) of 81.25%. In comparison, EUS showed a sensitivity of 87.50%, specificity of 85.19%, and a PPV of 77.78%. The combined use of OCT and EUS achieved a sensitivity of 93.75%, specificity of 92.59%, and a PPV of 88.24%.
Conclusions: The combined use of OCT and EUS can enhance sensitivity and specificity, thereby improving the accuracy of intraoperative navigation.
Trial registration: Chinese Clinical Trial Registry (No. ChiCTR2400088875); Registered 28 August 2024, first patient enrolled 20 September 2024.
{"title":"A Partially Randomized Diagnostic Trial of OCT-EUS Integration: Enhancing Surgical Margin Delineation and Lymph Node Dissection in Oncological Resection.","authors":"Yutao Wang, Lu Zhao, Jiahao Zhao, Xuanyu Wei, Daorong Wang, Jun Liu, Linjie Hu, Bing Xu, Jun Ji, Jiayi Zhang, Chaowu Chen, Dong Tang","doi":"10.1177/11795549251363829","DOIUrl":"10.1177/11795549251363829","url":null,"abstract":"<p><strong>Background: </strong>Accurate intraoperative navigation remains challenging in gastrointestinal tumor surgery. This study aims to explore the potential of optical coherence tomography (OCT) and endoscopic ultrasonography (EUS) in enhancing the accuracy of intraoperative navigation.</p><p><strong>Methods: </strong>This single-center diagnostic study was conducted at Northern Jiangsu People's Hospital from August to December 2024. This study is part of a prospective study, and more patients will be recruited in the future. The normal tissues, tumor tissues, vascular tissues, adipose tissues and lymph nodes of 12 patients with gastrointestinal tumors were collected for OCT and EUS scanning, and the image differences were compared. In addition, 43 lymph node specimens from 18 randomly selected patients were scanned by OCT and EUS, and pathological reports were used as the baseline. The results of OCT and EUS were compared retrospectively.</p><p><strong>Results: </strong>There are notable differences between OCT and EUS imaging. EUS can capture images of the entire tissue layer, making it more effective than OCT in assessing tumor invasion depth. Conversely, OCT serves as an \"optical biopsy,\" providing higher precision in the early stages of lesions. Our further research indicates that the combined application of these modalities holds significant potential. In a double-blind evaluation of 43 lymph nodes from 18 randomly selected patients, OCT demonstrated a sensitivity of 81.25%, specificity of 88.89%, and a positive predictive value (PPV) of 81.25%. In comparison, EUS showed a sensitivity of 87.50%, specificity of 85.19%, and a PPV of 77.78%. The combined use of OCT and EUS achieved a sensitivity of 93.75%, specificity of 92.59%, and a PPV of 88.24%.</p><p><strong>Conclusions: </strong>The combined use of OCT and EUS can enhance sensitivity and specificity, thereby improving the accuracy of intraoperative navigation.</p><p><strong>Trial registration: </strong>Chinese Clinical Trial Registry (No. ChiCTR2400088875); Registered 28 August 2024, first patient enrolled 20 September 2024.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"19 ","pages":"11795549251363829"},"PeriodicalIF":1.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-11eCollection Date: 2025-01-01DOI: 10.1177/11795549251371094
Mustafa Ersoy
Background: In non-small cell lung cancer (NSCLC) treatment, immunotherapy has become the standard therapy when platinum-based chemotherapy is ineffective, in the absence of a targetable mutation. However, a significant proportion of patients do not benefit from this treatment, underscoring the critical need for predictive biomarkers. This study aims to investigate the potential predictive role of immature granulocytes in response to nivolumab treatment, which can be used as a second-line therapy independent of programmed death ligand 1 (PDL-1) expression and other markers. Furthermore, the study seeks to determine whether there is a difference in the treatment response of immature granulocytes between the 2 main subtypes of NSCLC: lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD).
Methods: This retrospective study enrolled 50 patients with NSCLC who underwent treatment at the Kütahya Health Sciences University Evliya Çelebi Education and Research Hospital and Kütahya City Hospital between January 2021 and January 2025. The study examined the difference between patients' baseline immature granulocyte levels and their initial response to treatment, as assessed by positron emission tomography-computed tomography.
Results: The study found a statistically significant association between higher baseline immature granulocyte levels and poorer treatment response. Subgroup analysis by lung cancer subtype revealed that the difference was more prominent in the LUSCs group.
Conclusion: Immature granulocytes may predict response to nivolumab treatment in NSCLC patients, particularly in the LUSCs subgroup. Based on the findings of this study, immature granulocytes and other neutrophil-dependent inflammatory markers could serve as potential predictors of immunotherapy response and provide insights into the mechanisms of immunotherapy resistance, warranting further investigation. Our study may also encourage future research to look for separate markers for LUSCs and LUADs, given the continued critical need for predictive markers in this field.
{"title":"Immature Granulocytes and Nivolumab Outcomes in Stage IV Non-Small Cell Lung Cancer: Insights by Tumor Subtype.","authors":"Mustafa Ersoy","doi":"10.1177/11795549251371094","DOIUrl":"10.1177/11795549251371094","url":null,"abstract":"<p><strong>Background: </strong>In non-small cell lung cancer (NSCLC) treatment, immunotherapy has become the standard therapy when platinum-based chemotherapy is ineffective, in the absence of a targetable mutation. However, a significant proportion of patients do not benefit from this treatment, underscoring the critical need for predictive biomarkers. This study aims to investigate the potential predictive role of immature granulocytes in response to nivolumab treatment, which can be used as a second-line therapy independent of programmed death ligand 1 (PDL-1) expression and other markers. Furthermore, the study seeks to determine whether there is a difference in the treatment response of immature granulocytes between the 2 main subtypes of NSCLC: lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD).</p><p><strong>Methods: </strong>This retrospective study enrolled 50 patients with NSCLC who underwent treatment at the Kütahya Health Sciences University Evliya Çelebi Education and Research Hospital and Kütahya City Hospital between January 2021 and January 2025. The study examined the difference between patients' baseline immature granulocyte levels and their initial response to treatment, as assessed by positron emission tomography-computed tomography.</p><p><strong>Results: </strong>The study found a statistically significant association between higher baseline immature granulocyte levels and poorer treatment response. Subgroup analysis by lung cancer subtype revealed that the difference was more prominent in the LUSCs group.</p><p><strong>Conclusion: </strong>Immature granulocytes may predict response to nivolumab treatment in NSCLC patients, particularly in the LUSCs subgroup. Based on the findings of this study, immature granulocytes and other neutrophil-dependent inflammatory markers could serve as potential predictors of immunotherapy response and provide insights into the mechanisms of immunotherapy resistance, warranting further investigation. Our study may also encourage future research to look for separate markers for LUSCs and LUADs, given the continued critical need for predictive markers in this field.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"19 ","pages":"11795549251371094"},"PeriodicalIF":1.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12426404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-29eCollection Date: 2025-01-01DOI: 10.1177/11795549251364042
Adam E Singer, Nikhita Kathuria-Prakash, David Shabsovich, Lizette Garcia, Leland Damron, Allan J Pantuck, Alexandra Drakaki
Adrenocortical carcinoma is a rare, aggressive endocrine malignancy with limited effective systemic therapy options and an overall poor prognosis for unresectable or metastatic disease. Chemotherapy and mitotane are the traditional systemic therapies of choice. More recently, as drug development in oncology has shifted away from chemotherapy, a host of therapeutic approaches targeting novel mechanisms of action has been studied in adrenocortical carcinoma. This review summarizes all nonchemotherapeutic approaches that have been and/or are currently being tested in clinical trials for the treatment of unresectable or metastatic adrenocortical carcinoma.
{"title":"Frontiers in Systemic Therapy for Unresectable or Metastatic Adrenocortical Carcinoma: Harnessing Novel Therapeutic Approaches.","authors":"Adam E Singer, Nikhita Kathuria-Prakash, David Shabsovich, Lizette Garcia, Leland Damron, Allan J Pantuck, Alexandra Drakaki","doi":"10.1177/11795549251364042","DOIUrl":"10.1177/11795549251364042","url":null,"abstract":"<p><p>Adrenocortical carcinoma is a rare, aggressive endocrine malignancy with limited effective systemic therapy options and an overall poor prognosis for unresectable or metastatic disease. Chemotherapy and mitotane are the traditional systemic therapies of choice. More recently, as drug development in oncology has shifted away from chemotherapy, a host of therapeutic approaches targeting novel mechanisms of action has been studied in adrenocortical carcinoma. This review summarizes all nonchemotherapeutic approaches that have been and/or are currently being tested in clinical trials for the treatment of unresectable or metastatic adrenocortical carcinoma.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"19 ","pages":"11795549251364042"},"PeriodicalIF":1.9,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12397596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144974953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Multiple first-line chemotherapy-based combination regimens are available for patients with extensive-stage small cell lung cancer (ES-SCLC), however, direct head-to-head comparisons remain limited. This network meta-analysis (NMA) aimed to indirectly compare the efficacy and safety of various first-line combination therapies. Methods: A comprehensive literature search was conducted across electronic databases and academic conference proceedings to identify eligible randomized controlled trials (RCTs). Bayesian network meta-analysis and systematic review were performed on the selected studies. Primary outcomes included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR), along with adverse events of grade ⩾ 3 (grade ⩾ 3 AEs) and subgroup analyses. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022360249). Results: The analysis included 12 randomized trials encompassing 5840 patients and 14 treatment regimens. The combination of benmelstobart, anlotinib and chemotherapy showed the most significant improvement in PFS (hazard ratio [HR] = 0.33, 95% confidence interval [CI] = 0.26-0.41) and OS (HR = 0.61, 95% CI = 0.47-0.79) compared with chemotherapy alone. This regimen ranked highest for PFS (Bayesian ranking probability 99%) and OS (39%). However, it was also associated with a higher risk of Grade ⩾ 3 AEs (HR = 2.01, 95% CI = 1.09-3.73). In patients with baseline liver metastases, this regimen provided the greatest PFS benefit (99%), whereas serplulimab plus chemotherapy offered the best OS (53%). Conversely, for patients with baseline brain metastases, combination therapy failed to demonstrate a significant survival benefit. Conclusions: For treatment-naïve ES-SCLC patients, benmelstobart plus anlotinib plus chemotherapy yielded the most favorable outcomes in terms of PFS, OS and ORR, but a less favorable safety profile. These findings support its use as a potent therapeutic option in few patient populations.
{"title":"Efficacy and Safety of First-Line Chemotherapy-Based Combination Therapy for Patients With Extensive-Stage Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis.","authors":"Qingfang Zhao, Xiaomin Liu, Minghua Yu, Jinglong Chen","doi":"10.1177/11795549251364320","DOIUrl":"10.1177/11795549251364320","url":null,"abstract":"<p><p><b>Background:</b> Multiple first-line chemotherapy-based combination regimens are available for patients with extensive-stage small cell lung cancer (ES-SCLC), however, direct head-to-head comparisons remain limited. This network meta-analysis (NMA) aimed to indirectly compare the efficacy and safety of various first-line combination therapies. <b>Methods:</b> A comprehensive literature search was conducted across electronic databases and academic conference proceedings to identify eligible randomized controlled trials (RCTs). Bayesian network meta-analysis and systematic review were performed on the selected studies. Primary outcomes included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR), along with adverse events of grade ⩾ 3 (grade ⩾ 3 AEs) and subgroup analyses. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022360249). <b>Results:</b> The analysis included 12 randomized trials encompassing 5840 patients and 14 treatment regimens. The combination of benmelstobart, anlotinib and chemotherapy showed the most significant improvement in PFS (hazard ratio [HR] = 0.33, 95% confidence interval [CI] = 0.26-0.41) and OS (HR = 0.61, 95% CI = 0.47-0.79) compared with chemotherapy alone. This regimen ranked highest for PFS (Bayesian ranking probability 99%) and OS (39%). However, it was also associated with a higher risk of Grade ⩾ 3 AEs (HR = 2.01, 95% CI = 1.09-3.73). In patients with baseline liver metastases, this regimen provided the greatest PFS benefit (99%), whereas serplulimab plus chemotherapy offered the best OS (53%). Conversely, for patients with baseline brain metastases, combination therapy failed to demonstrate a significant survival benefit. <b>Conclusions:</b> For treatment-naïve ES-SCLC patients, benmelstobart plus anlotinib plus chemotherapy yielded the most favorable outcomes in terms of PFS, OS and ORR, but a less favorable safety profile. These findings support its use as a potent therapeutic option in few patient populations.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"19 ","pages":"11795549251364320"},"PeriodicalIF":1.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144974958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-20eCollection Date: 2025-01-01DOI: 10.1177/11795549251367498
Mustafa Ersoy
Background: Immunohistochemical results are of vital importance in the classification of patients with breast cancer into subgroups and in treatment decision-making at every stage. However, differences can occur in biopsy results obtained from the same patient. In our study, we aimed to investigate the importance of pathological examination, which is a possible reason for the differences in patients' immunohistochemistry results.
Methods: For this purpose, patients were divided into 3 groups. The differences in estrogen receptor, progesterone receptor, HER2, and Ki-67 were examined between the following groups: patients who received neoadjuvant chemotherapy and then underwent surgery (41 patients), patients who underwent surgery without chemotherapy (50 patients), and the same specimen from a different center and our center (21 patients).
Results: The pathological discordance rates were 34.1% in the neoadjuvant chemotherapy group, 28% in the surgery without chemotherapy group, and 38.1% in the comparison between our institution and an external center, with no statistically significant difference across the 3 groups (P = .667). When examining the changes within each group, statistically significant differences were found in HER2 (P = .002) for the tru-cut biopsy surgery group and Ki-67 (P = .025) for the group comparing our center to an external center.
Conclusions: As a result, it was considered that one of the important reasons for the immunohistochemical differences in breast biopsies, which is a known fact, is the evaluating center and pathologist.
{"title":"Discordance in Immunohistochemistry Results in Breast Pathologies: Effect of Chemotherapy, Specimen Characteristics, or Pathology Center?","authors":"Mustafa Ersoy","doi":"10.1177/11795549251367498","DOIUrl":"10.1177/11795549251367498","url":null,"abstract":"<p><strong>Background: </strong>Immunohistochemical results are of vital importance in the classification of patients with breast cancer into subgroups and in treatment decision-making at every stage. However, differences can occur in biopsy results obtained from the same patient. In our study, we aimed to investigate the importance of pathological examination, which is a possible reason for the differences in patients' immunohistochemistry results.</p><p><strong>Methods: </strong>For this purpose, patients were divided into 3 groups. The differences in estrogen receptor, progesterone receptor, HER2, and Ki-67 were examined between the following groups: patients who received neoadjuvant chemotherapy and then underwent surgery (41 patients), patients who underwent surgery without chemotherapy (50 patients), and the same specimen from a different center and our center (21 patients).</p><p><strong>Results: </strong>The pathological discordance rates were 34.1% in the neoadjuvant chemotherapy group, 28% in the surgery without chemotherapy group, and 38.1% in the comparison between our institution and an external center, with no statistically significant difference across the 3 groups (<i>P</i> = .667). When examining the changes within each group, statistically significant differences were found in HER2 (<i>P</i> = .002) for the tru-cut biopsy surgery group and Ki-67 (<i>P</i> = .025) for the group comparing our center to an external center.</p><p><strong>Conclusions: </strong>As a result, it was considered that one of the important reasons for the immunohistochemical differences in breast biopsies, which is a known fact, is the evaluating center and pathologist.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"19 ","pages":"11795549251367498"},"PeriodicalIF":1.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12368330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144974987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Intrahepatic cholangiocarcinoma (ICC) is a primary liver cancer typically diagnosed at advanced stages, limiting treatment options and reducing survival rates. Targeted therapy presents a promising strategy to improve outcomes. This study aims to identify novel molecular biomarkers influencing ICC development and explore their roles in tumor progression.
Methods: Data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed using weighted gene co-expression network analysis (WGCNA) to identify genes related to tumor metastasis and recurrence. Survival analysis and gene set enrichment analysis (GSEA) assessed the relationship between gene expression and survival, as well as associated signaling pathways. Cellular experiments, including small interfering RNA (siRNA) knockdown, cell viability assays, Transwell migration assays, and flow cytometry, were performed.
Results: The Kaplan-Meier analysis showed that ICC patients with high N-acetyltransferase 2 (NAT2) expression had significantly shorter survival times than those with low expression (P < .001). Gene set enrichment analysis revealed enrichment of MYC and MTORC1 pathways, linked to tumor proliferation, and E2F and G2M pathways, which regulate the cell cycle, in high NAT2 expression samples (P < .01). The NAT2 knockdown reduced RBE cell proliferation (P < .001) and increased late apoptosis (P < .001). Immunofluorescence analysis showed increased Bax and Caspase-3 expression and decreased BCL-2 expression (P < .05), supporting NAT2's role in regulating ICC cell apoptosis.
Conclusion: NAT2, a novel therapeutic target, holds significant potential to improve the prognosis of ICC patients.
背景:肝内胆管癌(ICC)是一种原发性肝癌,通常在晚期诊断,限制了治疗选择并降低了生存率。靶向治疗是一种改善预后的有希望的策略。本研究旨在发现影响ICC发展的新型分子生物标志物,并探讨其在肿瘤进展中的作用。方法:采用加权基因共表达网络分析(WGCNA)对来自癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)的数据进行分析,找出与肿瘤转移和复发相关的基因。生存分析和基因集富集分析(GSEA)评估基因表达与生存的关系,以及相关的信号通路。进行细胞实验,包括小干扰RNA (siRNA)敲除、细胞活力测定、Transwell迁移测定和流式细胞术。结果:Kaplan-Meier分析显示,n-乙酰转移酶2 (NAT2)高表达的ICC患者的生存时间明显短于低表达的ICC患者(P P P P P P P)。结论:NAT2是一种新的治疗靶点,具有显著改善ICC患者预后的潜力。
{"title":"<i>NAT2</i>: A Novel Target in Intrahepatic Cholangiocarcinoma and its Role in Modulating Tumor Behavior.","authors":"Xiyun Chen, Guang Yang, Cheng Lou, Yulong Dong, Zhengang Yuan","doi":"10.1177/11795549251360481","DOIUrl":"10.1177/11795549251360481","url":null,"abstract":"<p><strong>Background: </strong>Intrahepatic cholangiocarcinoma (ICC) is a primary liver cancer typically diagnosed at advanced stages, limiting treatment options and reducing survival rates. Targeted therapy presents a promising strategy to improve outcomes. This study aims to identify novel molecular biomarkers influencing ICC development and explore their roles in tumor progression.</p><p><strong>Methods: </strong>Data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed using weighted gene co-expression network analysis (WGCNA) to identify genes related to tumor metastasis and recurrence. Survival analysis and gene set enrichment analysis (GSEA) assessed the relationship between gene expression and survival, as well as associated signaling pathways. Cellular experiments, including small interfering RNA (siRNA) knockdown, cell viability assays, Transwell migration assays, and flow cytometry, were performed.</p><p><strong>Results: </strong>The Kaplan-Meier analysis showed that ICC patients with high N-acetyltransferase 2 (NAT2) expression had significantly shorter survival times than those with low expression (<i>P</i> < .001). Gene set enrichment analysis revealed enrichment of MYC and MTORC1 pathways, linked to tumor proliferation, and E2F and G2M pathways, which regulate the cell cycle, in high NAT2 expression samples (<i>P</i> < .01). The NAT2 knockdown reduced RBE cell proliferation (<i>P</i> < .001) and increased late apoptosis (<i>P</i> < .001). Immunofluorescence analysis showed increased Bax and Caspase-3 expression and decreased BCL-2 expression (<i>P</i> < .05), supporting NAT2's role in regulating ICC cell apoptosis.</p><p><strong>Conclusion: </strong>NAT2, a novel therapeutic target, holds significant potential to improve the prognosis of ICC patients.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"19 ","pages":"11795549251360481"},"PeriodicalIF":1.9,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12358714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144884131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The eradication of tumors remains a critical and challenging issue in medical research. Exosomes (EXOs) derived from various sources have garnered increasing attention in the field of tumor therapy. Among these, cord blood (CB)-derived EXOs may offer unique advantages in combating tumors due to the distinctive properties of CB. This narrative review examines the current application status of CB-derived EXOs in tumor prevention and treatment: in the context of tumor treatment, it focuses on their direct therapeutic application and their use as drug carriers; regarding tumor prevention, it explores their application in cancer vaccines. In addition, it also reviews the specific components of CB from which these EXOs are derived, their particle sizes, characteristic proteins, and the types of tumors to which they have been primarily applied for prevention and treatment. In conclusion, we believe that CB-derived EXOs hold substantial potential for effective tumor prevention and treatment and are likely to emerge as a prominent area of research in the future.
{"title":"Application of Cord Blood-Derived Exosomes in Tumor Prevention and Treatment.","authors":"Chen Huang, Yongsheng Li, Baozhong Zhang, Yukuan Tang, Yuyang Huang, Wei Wei","doi":"10.1177/11795549251365360","DOIUrl":"10.1177/11795549251365360","url":null,"abstract":"<p><p>The eradication of tumors remains a critical and challenging issue in medical research. Exosomes (EXOs) derived from various sources have garnered increasing attention in the field of tumor therapy. Among these, cord blood (CB)-derived EXOs may offer unique advantages in combating tumors due to the distinctive properties of CB. This narrative review examines the current application status of CB-derived EXOs in tumor prevention and treatment: in the context of tumor treatment, it focuses on their direct therapeutic application and their use as drug carriers; regarding tumor prevention, it explores their application in cancer vaccines. In addition, it also reviews the specific components of CB from which these EXOs are derived, their particle sizes, characteristic proteins, and the types of tumors to which they have been primarily applied for prevention and treatment. In conclusion, we believe that CB-derived EXOs hold substantial potential for effective tumor prevention and treatment and are likely to emerge as a prominent area of research in the future.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"19 ","pages":"11795549251365360"},"PeriodicalIF":1.9,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12340371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: This study investigates the potential of purine nucleoside phosphorylase (PNP) as a biomarker and therapeutic target in muscle-invasive bladder cancer (MIBC). We aimed to explore PNP's expression, prognostic value, and role in metabolic pathways, along with its association with gene mutations.
Methods: We conducted multi-omics analyses using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and other public databases to evaluate PNP expression across MIBC samples and its prognostic impact through Kaplan-Meier and Cox regression analyses. Functional enrichment and gene set variation analysis (GSVA) were performed to identify PNP-related pathways. In addition, in vitro siRNA knockdown experiments were carried out to assess PNP's influence on MIBC cell proliferation.
Results: Our findings revealed that PNP is significantly overexpressed in MIBC tissues and serves as an independent prognostic factor, correlating with poor clinical outcomes across multiple cohorts (TCGA: hazard ratio [HR] > 1.3, P < .05; GSE48075: HR > 1.5, P = .07; GSE169455: HR > 2.8, P < .001). Functional enrichment analysis identified PNP's involvement in various metabolic pathways. Furthermore, we observed a high frequency of RB1 mutations in the PNP-high expression group. Based on this observation, we hypothesize that patients harboring RB1 mutations may benefit from PNP-targeted therapy. In vitro experiments demonstrated that PNP knockdown significantly reduces MIBC cell proliferation.
Conclusion: This study underscores PNP's role as a promising biomarker and therapeutic target in MIBC.
背景:本研究探讨了嘌呤核苷磷酸化酶(PNP)作为肌肉浸润性膀胱癌(MIBC)的生物标志物和治疗靶点的潜力。我们的目的是探讨PNP的表达、预后价值、在代谢途径中的作用,以及它与基因突变的关系。方法:利用来自癌症基因组图谱(TCGA)、基因表达图谱(GEO)等公共数据库的数据进行多组学分析,通过Kaplan-Meier和Cox回归分析评估PNP在MIBC样本中的表达及其对预后的影响。通过功能富集和基因集变异分析(GSVA)鉴定pnp相关通路。此外,我们还进行了体外siRNA敲低实验,以评估PNP对MIBC细胞增殖的影响。结果:我们的研究结果显示,PNP在MIBC组织中显著过表达,并作为一个独立的预后因素,与多个队列的不良临床结果相关(TCGA:风险比[HR] > 1.3, p1.5, P = .07;结论:该研究强调了PNP作为MIBC中有前景的生物标志物和治疗靶点的作用。
{"title":"Purine Nucleoside Phosphorylase (PNP) as a Biomarker and Therapeutic Target in Muscle-Invasive Bladder Cancer.","authors":"Yanfei Chen, Peiyi Xian, Jianming Lu, Le Zhang, Chao Cai, Weide Zhong","doi":"10.1177/11795549251359145","DOIUrl":"10.1177/11795549251359145","url":null,"abstract":"<p><strong>Background: </strong>This study investigates the potential of purine nucleoside phosphorylase (PNP) as a biomarker and therapeutic target in muscle-invasive bladder cancer (MIBC). We aimed to explore PNP's expression, prognostic value, and role in metabolic pathways, along with its association with gene mutations.</p><p><strong>Methods: </strong>We conducted multi-omics analyses using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and other public databases to evaluate PNP expression across MIBC samples and its prognostic impact through Kaplan-Meier and Cox regression analyses. Functional enrichment and gene set variation analysis (GSVA) were performed to identify PNP-related pathways. In addition, <i>in vitro</i> siRNA knockdown experiments were carried out to assess PNP's influence on MIBC cell proliferation.</p><p><strong>Results: </strong>Our findings revealed that PNP is significantly overexpressed in MIBC tissues and serves as an independent prognostic factor, correlating with poor clinical outcomes across multiple cohorts (TCGA: hazard ratio [HR] > 1.3, <i>P</i> < .05; GSE48075: HR > 1.5, <i>P</i> = .07; GSE169455: HR > 2.8, <i>P</i> < .001). Functional enrichment analysis identified PNP's involvement in various metabolic pathways. Furthermore, we observed a high frequency of RB1 mutations in the PNP-high expression group. Based on this observation, we hypothesize that patients harboring RB1 mutations may benefit from PNP-targeted therapy. In vitro experiments demonstrated that PNP knockdown significantly reduces MIBC cell proliferation.</p><p><strong>Conclusion: </strong>This study underscores PNP's role as a promising biomarker and therapeutic target in MIBC.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"19 ","pages":"11795549251359145"},"PeriodicalIF":1.9,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12340192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: This study aimed to determine the prognostic effect of the serum vitamin B12 level/CRP ratio (BCR) on patients diagnosed with solid cancer.
Methods: Patients >18 years diagnosed with solid cancer were included in the study, the data of the patients were retrospectively examined, and the cut-off values for BCR were determined using receiver operating characteristic (ROC) analysis. Accordingly, grouping was performed, appropriate statistical analyses were performed, and P < .05 was accepted as the significance limit value.
Results: The median age of the 344 patients included in the study was found to be 60.9 (range: 27-88) years. Around 56.6% (n = 174) of the patients had nondistant metastatic group and 49.4% (n = 170) had metastatic group. The median follow-up period of the patients was found to be 46.8 (range: 4-63) months. In the metastatic group, mortality was statistically significantly 2.1 times higher in those with a BCR cut-off value <3.5 (95% confidence interval [CI]; 1.4-3.2, P < .001). In the nonmetastatic group, mortality was statistically significantly twice higher in those with a BCR cut-off value <3.8 (95% CI; 1.4-3.3, P < .001). In addition, mortality was statistically significantly higher in high-risk patients in the nonmetastatic group (63.8% (n = 188) vs 45.5% (n = 156) (P < .001). The mOS period for patients in the high-risk group was 42.8 ± 1.4 (95% CI: 40.1-45.5) months, the mOS period for patients in the low-risk group was 51.5 ± 1.3 (95% CI: 49.0-54.0) months, and the mOS period for the entire group was 46.8 ± 1.0 (95% CI: 44.8-48.7) months (P < .001).
Conclusıons: In conclusion, our study has shown that BCR, which has not been reported in the literature to date, is one of the cheapest and easily accessible inflammation markers that can determine prognosis in cancer patients.
背景:本研究旨在确定血清维生素B12水平/CRP比值(BCR)对确诊实体癌患者预后的影响。方法:选取年龄在bb0 ~ 18岁确诊为实体癌的患者,对患者资料进行回顾性分析,采用受试者工作特征(receiver operating characteristic, ROC)分析确定BCR的临界值。结果:纳入研究的344例患者中位年龄为60.9岁(范围:27-88岁)。非远处转移组占56.6% (n = 174),转移组占49.4% (n = 170)。患者的中位随访时间为46.8个月(范围4-63个月)。在转移组中,BCR临界值P P P P P Conclusıons的死亡率具有统计学意义,高出2.1倍:总之,我们的研究表明,迄今为止尚未在文献中报道的BCR是最便宜且易于获取的炎症标志物之一,可以确定癌症患者的预后。
{"title":"The Prognostic Value of B12/CRP Ratio (BCR) in Patients Diagnosed With Solid Cancer.","authors":"Merve Keskinkilic, Elif Cetin Basaran, Tugba Yavuzsen","doi":"10.1177/11795549251360891","DOIUrl":"10.1177/11795549251360891","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to determine the prognostic effect of the serum vitamin B12 level/CRP ratio (BCR) on patients diagnosed with solid cancer.</p><p><strong>Methods: </strong>Patients >18 years diagnosed with solid cancer were included in the study, the data of the patients were retrospectively examined, and the cut-off values for BCR were determined using receiver operating characteristic (ROC) analysis. Accordingly, grouping was performed, appropriate statistical analyses were performed, and <i>P</i> < .05 was accepted as the significance limit value.</p><p><strong>Results: </strong>The median age of the 344 patients included in the study was found to be 60.9 (range: 27-88) years. Around 56.6% (n = 174) of the patients had nondistant metastatic group and 49.4% (n = 170) had metastatic group. The median follow-up period of the patients was found to be 46.8 (range: 4-63) months. In the metastatic group, mortality was statistically significantly 2.1 times higher in those with a BCR cut-off value <3.5 (95% confidence interval [CI]; 1.4-3.2, <i>P</i> < .001). In the nonmetastatic group, mortality was statistically significantly twice higher in those with a BCR cut-off value <3.8 (95% CI; 1.4-3.3, <i>P</i> < .001). In addition, mortality was statistically significantly higher in high-risk patients in the nonmetastatic group (63.8% (n = 188) vs 45.5% (n = 156) (<i>P</i> < .001). The mOS period for patients in the high-risk group was 42.8 ± 1.4 (95% CI: 40.1-45.5) months, the mOS period for patients in the low-risk group was 51.5 ± 1.3 (95% CI: 49.0-54.0) months, and the mOS period for the entire group was 46.8 ± 1.0 (95% CI: 44.8-48.7) months (<i>P</i> < .001).</p><p><strong>Conclusıons: </strong>In conclusion, our study has shown that BCR, which has not been reported in the literature to date, is one of the cheapest and easily accessible inflammation markers that can determine prognosis in cancer patients.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"19 ","pages":"11795549251360891"},"PeriodicalIF":1.9,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12340191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}