Ibrahim Ibrahim, Omar Kouli, Sanjana Ilangovan, Melanie Sneddon, Sarika Nalagatla, Carol Marshall, Lorenzo Dutto, Hing Y. Leung, Imran Ahmad
Background
To assess how centralisation of cancer services via robotic surgery influenced positive surgical margin (PSM) occurrence and its associated risk of biochemical recurrence (BCR) in cases of pT2 prostate cancer (PC).
Methods
Retrospective analysis of all radical prostatectomy (RP) cases performed in the West of Scotland during the period from January 2013 to June 2022. Primary outcomes were PSM and BCR. The secondary outcomes compared the impact of centralisation and surgical approach on PSM and BCR; and margin length and location on BCR. Propensity score matching and Cox regression models were performed using R.
Results
A total of, 907 patients were included; 662 robot assisted radical prostatectomy (RARP), 245 open RP. PSM rate was 17.7% (161/907), similar in RARP and open cohorts. Patients with PSM had higher rates of BCR; 26.7%, compared to 8.7% in patients with no PSM. Patients with margins of ≥ 1 mm had higher risk of developing BCR. Patients who underwent open RP had increased incidence of PSM ≥ 1 mm; 40/43 (93%) compared to 83/117 (71%) in robotic approach (p = 0.003). Limitations include the study being retrospective, introduction of centralisation and robot concurrently, and evolution of practice.
Discussion
PSMs in pT2 PC are associated with higher rates of BCR. Introduction of centralisation via the robot had no impact on PSM occurrence or BCR, although did demonstrate a reduction in PSM length.
{"title":"Impact of Centralisation of Radical Prostatectomy Driven by the Introduction of Robotic Systems on Positive Surgical Margin and Biochemical Recurrence in pT2 Prostate Cancer","authors":"Ibrahim Ibrahim, Omar Kouli, Sanjana Ilangovan, Melanie Sneddon, Sarika Nalagatla, Carol Marshall, Lorenzo Dutto, Hing Y. Leung, Imran Ahmad","doi":"10.1002/cam4.70514","DOIUrl":"10.1002/cam4.70514","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>To assess how centralisation of cancer services via robotic surgery influenced positive surgical margin (PSM) occurrence and its associated risk of biochemical recurrence (BCR) in cases of pT2 prostate cancer (PC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Retrospective analysis of all radical prostatectomy (RP) cases performed in the West of Scotland during the period from January 2013 to June 2022. Primary outcomes were PSM and BCR. The secondary outcomes compared the impact of centralisation and surgical approach on PSM and BCR; and margin length and location on BCR. Propensity score matching and Cox regression models were performed using R.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of, 907 patients were included; 662 robot assisted radical prostatectomy (RARP), 245 open RP. PSM rate was 17.7% (161/907), similar in RARP and open cohorts. Patients with PSM had higher rates of BCR; 26.7%, compared to 8.7% in patients with no PSM. Patients with margins of ≥ 1 mm had higher risk of developing BCR. Patients who underwent open RP had increased incidence of PSM ≥ 1 mm; 40/43 (93%) compared to 83/117 (71%) in robotic approach (<i>p</i> = 0.003). Limitations include the study being retrospective, introduction of centralisation and robot concurrently, and evolution of practice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>PSMs in pT2 PC are associated with higher rates of BCR. Introduction of centralisation via the robot had no impact on PSM occurrence or BCR, although did demonstrate a reduction in PSM length.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent and lethal malignancies worldwide. Despite progress in immunotherapy for cancer treatment, its application and efficacy in ESCC remain limited. Therefore, there is an ongoing need to explore potential molecules and therapeutic strategies related to tumor immunity in ESCC.
Methods
In this study, we integrated high-throughput sequencing data, gene chip data, single-cell sequencing data, and various bioinformatics analysis methods along with experimental approaches to identify key genes involved in immune infiltration in ESCC and investigate their relationship with immune cell development, as well as the potential of these key genes in immunotherapy.
Results
We discovered and validated a positive correlation between macrophage infiltration and ITGB2 expression in ESCC. ITGB2 is overexpressed in ESCC and has potential as a prognostic biomarker for the disease. We present for the first time the finding that the expression of ITGB2 in infiltrating macrophages increases as these macrophages polarize toward a tumor-promoting phenotype in ESCC. Moreover, during the progression of ESCC, ITGB2 expression in infiltrating macrophages is upregulated. The higher the expression of ITGB2, the more feasible it is to target macrophages. Additionally, we found that evaluating immune therapy responses in ESCC patients through ITGB2 expression is a viable approach. Furthermore, we identified three miRNAs associated with abnormal ITGB2 expression, providing insights into the upstream molecular interactions of ITGB2.
Conclusions
Macrophage infiltration in ESCC is closely associated with ITGB2, which holds significant potential for immunotherapy applications in ESCC. Based on our findings and prior studies, we propose a novel hypothesis: inducing M1 macrophages in vitro, knocking out ITGB2, and then reinfusing these ITGB2-knockout M1 macrophages into ESCC patients may represent a promising new immunotherapy strategy, providing a new avenue for ESCC immunotherapy.
{"title":"Macrophage Infiltration and ITGB2 Expression in ESCC: A Novel Correlation","authors":"Tao Huang, Longqian Wei, Huafu Zhou, Jun Liu","doi":"10.1002/cam4.70604","DOIUrl":"10.1002/cam4.70604","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent and lethal malignancies worldwide. Despite progress in immunotherapy for cancer treatment, its application and efficacy in ESCC remain limited. Therefore, there is an ongoing need to explore potential molecules and therapeutic strategies related to tumor immunity in ESCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we integrated high-throughput sequencing data, gene chip data, single-cell sequencing data, and various bioinformatics analysis methods along with experimental approaches to identify key genes involved in immune infiltration in ESCC and investigate their relationship with immune cell development, as well as the potential of these key genes in immunotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We discovered and validated a positive correlation between macrophage infiltration and ITGB2 expression in ESCC. ITGB2 is overexpressed in ESCC and has potential as a prognostic biomarker for the disease. We present for the first time the finding that the expression of ITGB2 in infiltrating macrophages increases as these macrophages polarize toward a tumor-promoting phenotype in ESCC. Moreover, during the progression of ESCC, ITGB2 expression in infiltrating macrophages is upregulated. The higher the expression of ITGB2, the more feasible it is to target macrophages. Additionally, we found that evaluating immune therapy responses in ESCC patients through ITGB2 expression is a viable approach. Furthermore, we identified three miRNAs associated with abnormal ITGB2 expression, providing insights into the upstream molecular interactions of ITGB2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Macrophage infiltration in ESCC is closely associated with ITGB2, which holds significant potential for immunotherapy applications in ESCC. Based on our findings and prior studies, we propose a novel hypothesis: inducing M1 macrophages in vitro, knocking out ITGB2, and then reinfusing these ITGB2-knockout M1 macrophages into ESCC patients may represent a promising new immunotherapy strategy, providing a new avenue for ESCC immunotherapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoyu Ji, Siyuan Yang, Dejing Cheng, Wenbo Zhao, Xuebo Sun, Fang Su
Purpose
This study aimed to identify prognostic factors and develop a nomogram for survival in patients with brainstem ependymoma.
Methods
Data of 652 patients diagnosed with brainstem ependymoma extracted from the Surveillance, Epidemiology, and End Results (SEER) registry from 2000 to 2020 were analyzed. Univariate and multivariable Cox regression analyses were performed to examine factors influencing overall survival (OS). Receiver operating characteristic curve (ROC) and calibration curves were used to verify the nomogram. The Kaplan–Meier method was used to analyze OS based on treatment methods stratification or different age patterns.
Results
Six independent prognostic factors of patients with brainstem ependymoma were identified, including age, race, marital status, radiation, gross total resection (GTR), and histology. A comprehensive nomogram model was developed utilizing these predictors identified through multivariable Cox regression analysis. Furthermore, we found that patients with GTR have improved overall survival than patient with no surgery and biopsy only or with partial resection (GTR vs. no: p = 0.0004, GTR vs. partial resection: p = 0.022). Patients with radiation have improved overall survival than patient without radiation (p = 0.00013). Patients with GTR combined radiation therapy have improved overall survival than patient without or with GTR or radiation therapy only (p < 0.0001). Different treatment methods have no significant difference in the overall survival probability of the elderly group.
Conclusions
Individuals who are Black and anaplastic ependymomas were negative risk factors for brainstem ependymoma associated with an increased risk of mortality. Patients aged < 50 years with GTR and radiation always had better survival.
{"title":"Prognostic Factors and Nomogram for Malignant Brainstem Ependymoma: A Population-Based Retrospective Surveillance, Epidemiology, and End Results Database Analysis","authors":"Xiaoyu Ji, Siyuan Yang, Dejing Cheng, Wenbo Zhao, Xuebo Sun, Fang Su","doi":"10.1002/cam4.70564","DOIUrl":"10.1002/cam4.70564","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>This study aimed to identify prognostic factors and develop a nomogram for survival in patients with brainstem ependymoma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data of 652 patients diagnosed with brainstem ependymoma extracted from the Surveillance, Epidemiology, and End Results (SEER) registry from 2000 to 2020 were analyzed. Univariate and multivariable Cox regression analyses were performed to examine factors influencing overall survival (OS). Receiver operating characteristic curve (ROC) and calibration curves were used to verify the nomogram. The Kaplan–Meier method was used to analyze OS based on treatment methods stratification or different age patterns.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Six independent prognostic factors of patients with brainstem ependymoma were identified, including age, race, marital status, radiation, gross total resection (GTR), and histology. A comprehensive nomogram model was developed utilizing these predictors identified through multivariable Cox regression analysis. Furthermore, we found that patients with GTR have improved overall survival than patient with no surgery and biopsy only or with partial resection (GTR vs. no: <i>p</i> = 0.0004, GTR vs. partial resection: <i>p</i> = 0.022). Patients with radiation have improved overall survival than patient without radiation (<i>p</i> = 0.00013). Patients with GTR combined radiation therapy have improved overall survival than patient without or with GTR or radiation therapy only (<i>p</i> < 0.0001). Different treatment methods have no significant difference in the overall survival probability of the elderly group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Individuals who are Black and anaplastic ependymomas were negative risk factors for brainstem ependymoma associated with an increased risk of mortality. Patients aged < 50 years with GTR and radiation always had better survival.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alireza Ramandi, Jacob George, Amir Hossein Behnoush, Alireza Delavari, Zahra Mohammadi, Hossein Poustchi, Reza Malekzadeh
Background
Gamma-glutamyl transferase (GGT) has been shown to have associations with several diseases including cancers. Previous studies have investigated the effect of GGT levels on the gastrointestinal (GI) cancer incidence. We aim to systematically investigate these studies to provide better insights into the interrelationship between GGT and GI cancers.
Methods
Online databases were searched to find relevant studies investigating different GGT levels' effects on the incidence of GI cancers including colorectal, esophageal, liver, pancreas, gastric, and biliary duct cancers. Random-effect meta-analysis was conducted to pool the hazard ratios (HRs) of GGT quartiles (Qs) effect on cancer incidence.
Results
A total of 26 studies were included in the final review, 12 of which underwent meta-analysis that investigated 11 million patients. Based on the meta-analysis, Q4 patients had a 69% higher hazard of GI cancer incidence (HR 1.69, 95% CI 1.41–2.02, p-value < 0.001). The hazard ratio significance was also similar for Q3 (HR 1.22, 95% CI 1.15–1.30, p-value < 0.001) and Q2 (HR 1.10, 95% CI 1.05–1.16, p-value =0.002) of GGT. Colorectal and liver cancers showed a higher hazard ratio among Q2, Q3, and Q4 of GGT compared to Q1. In pancreas and bile duct cancers, only Q4 of GGT had significantly higher HR. Q3 and Q4 of GGT levels had statistically significant associations with gastric cancer incidence.
Conclusion
Higher GGT levels correlate with higher rates of GI cancer incidence, especially in colorectal and hepatic cancers. Future studies should investigate this biomarker's potential role in risk assessment for digestive cancers.
背景：γ -谷氨酰转移酶（GGT）已被证明与包括癌症在内的几种疾病有关。以往的研究调查了GGT水平对胃肠道（GI）癌症发病率的影响。我们的目标是系统地调查这些研究，以更好地了解GGT和GI癌症之间的相互关系。方法：检索在线数据库，查找不同GGT水平对大肠癌、食管癌、肝癌、胰腺癌、胃癌、胆管癌等胃肠道肿瘤发病率影响的相关研究。随机效应荟萃分析GGT四分位数（Qs）对癌症发病率影响的风险比（hr）。结果：最终综述共纳入26项研究，其中12项进行了荟萃分析，调查了1100万患者。基于荟萃分析，Q4患者胃肠道肿瘤发病率增高69% （HR 1.69, 95% CI 1.41-2.02， p值）。结论：GGT水平升高与胃肠道肿瘤发病率增高相关，尤其是结直肠癌和肝癌。未来的研究应该探讨这种生物标志物在消化道癌症风险评估中的潜在作用。
{"title":"The Association Between Serum Gamma-Glutamyl Transferase and Gastrointestinal Cancer Risk: A Systematic Review and Meta-Analysis","authors":"Alireza Ramandi, Jacob George, Amir Hossein Behnoush, Alireza Delavari, Zahra Mohammadi, Hossein Poustchi, Reza Malekzadeh","doi":"10.1002/cam4.70581","DOIUrl":"10.1002/cam4.70581","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Gamma-glutamyl transferase (GGT) has been shown to have associations with several diseases including cancers. Previous studies have investigated the effect of GGT levels on the gastrointestinal (GI) cancer incidence. We aim to systematically investigate these studies to provide better insights into the interrelationship between GGT and GI cancers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Online databases were searched to find relevant studies investigating different GGT levels' effects on the incidence of GI cancers including colorectal, esophageal, liver, pancreas, gastric, and biliary duct cancers. Random-effect meta-analysis was conducted to pool the hazard ratios (HRs) of GGT quartiles (Qs) effect on cancer incidence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 26 studies were included in the final review, 12 of which underwent meta-analysis that investigated 11 million patients. Based on the meta-analysis, Q4 patients had a 69% higher hazard of GI cancer incidence (HR 1.69, 95% CI 1.41–2.02, <i>p</i>-value < 0.001). The hazard ratio significance was also similar for Q3 (HR 1.22, 95% CI 1.15–1.30, <i>p</i>-value < 0.001) and Q2 (HR 1.10, 95% CI 1.05–1.16, <i>p</i>-value =0.002) of GGT. Colorectal and liver cancers showed a higher hazard ratio among Q2, Q3, and Q4 of GGT compared to Q1. In pancreas and bile duct cancers, only Q4 of GGT had significantly higher HR. Q3 and Q4 of GGT levels had statistically significant associations with gastric cancer incidence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Higher GGT levels correlate with higher rates of GI cancer incidence, especially in colorectal and hepatic cancers. Future studies should investigate this biomarker's potential role in risk assessment for digestive cancers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The use of digital health strategies for cancer care increased dramatically in the United States over the past 4 years. However, a dearth of knowledge remains about the use of digital health for cancer prevention for some populations with heath disparities. Therefore, the purpose of the present scoping review was to identify digital health interventions for cancer prevention designed for people with disabilities.
Methods
This scoping review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews and the Arksey and O'Malley methodological framework. The Embase, PubMed, Ovid MEDLINE, and CINAHL/EBSCO databases were searched for peer-reviewed articles published from database inception to February 5, 2024. Reports published in English of studies that employed digital health strategies for cancer prevention, were conducted among people with disabilities regardless of age, and were conducted in the United States were included.
Findings
Following screening for eligibility, seven articles were identified. The types of disabilities were cancer (n = 4), bipolar I or II disorder (n = 1), obesity (n = 1), and deafness (n = 1). Interventions focused on education (n = 4), screening (n = 3), smoking cessation (n = 3), physical activity (n = 1), and cessation support (n = 1). Digital health strategies consisted of educational content delivered online, text messaging, interactive educational games, and downloadable informational applications. The common outcome of interest across all manuscripts was intervention efficacy.
Interpretation
Overall, limited research is available to evaluate the use of digital health for cancer prevention among people with disabilities. This review identified gaps in knowledge that, if addressed, may help guide continued innovation in the use of digital health strategies for cancer prevention among people with disabilities.
{"title":"Use of Digital Health Interventions for Cancer Prevention Among People Living With Disabilities in the United States: A Scoping Review","authors":"Chinenye Lynette Ejezie, Lea Sacca, Sylvia Ayieko, Sara Burgoa, Yasmine Zerrouki, Diana Lobaina, Goodness Okwaraji, Christine Markham","doi":"10.1002/cam4.70571","DOIUrl":"10.1002/cam4.70571","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The use of digital health strategies for cancer care increased dramatically in the United States over the past 4 years. However, a dearth of knowledge remains about the use of digital health for cancer prevention for some populations with heath disparities. Therefore, the purpose of the present scoping review was to identify digital health interventions for cancer prevention designed for people with disabilities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This scoping review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews and the Arksey and O'Malley methodological framework. The Embase, PubMed, Ovid MEDLINE, and CINAHL/EBSCO databases were searched for peer-reviewed articles published from database inception to February 5, 2024. Reports published in English of studies that employed digital health strategies for cancer prevention, were conducted among people with disabilities regardless of age, and were conducted in the United States were included.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>Following screening for eligibility, seven articles were identified. The types of disabilities were cancer (<i>n</i> = 4), bipolar I or II disorder (<i>n</i> = 1), obesity (<i>n</i> = 1), and deafness (<i>n</i> = 1). Interventions focused on education (<i>n</i> = 4), screening (<i>n</i> = 3), smoking cessation (<i>n</i> = 3), physical activity (<i>n</i> = 1), and cessation support (<i>n</i> = 1). Digital health strategies consisted of educational content delivered online, text messaging, interactive educational games, and downloadable informational applications. The common outcome of interest across all manuscripts was intervention efficacy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Overall, limited research is available to evaluate the use of digital health for cancer prevention among people with disabilities. This review identified gaps in knowledge that, if addressed, may help guide continued innovation in the use of digital health strategies for cancer prevention among people with disabilities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lymphatic metastasis in gastric cancer (GC) profoundly influences its prognosis, but the precise mechanism remains elusive. In this study, we identified the long noncoding RNA MIR181A2HG as being upregulated in GC and associated with LNs metastasis and prognosis.
Methods
The expression of MIR181A2HG in GC was identified through bioinformatics screening analysis and qRT-PCR validation. Both in vitro and in vivo functional studies revealed that MIR181A2HG facilitates lymphangiogenesis and lymphatic metastasis. Techniques such as immunofluorescence, immunohistochemistry, qRT-PCR, ELISA, CHIP, RNA-pulldown, luciferase reporter assay, and Co-IP were employed to investigate the mechanism of MIR181A2HG in LNs metastasis of GC.
Results
MIR181A2HG overexpressed in GC signifies an unfavorable prognosis and drives M2 polarization of TAMs enhancing lymphangiogenesis. Mechanistically, MIR181A2HG/miR-5680 axis as a novel ceRNA regulatory axis to upregulate versican (VCAN). On one hand, VCAN interacts with CD44 receptors on the surface of TAMs through paracrine secretion, promoting M2 macrophage polarization and subsequently enhancing the secretion of VEGF-C, ultimately facilitating lymphangiogenesis. On the other hand, VCAN binds to CD44 receptors on the surface of GC cells through autocrine secretion, activating the Hippo pathway and upregulating SP1, thereby promoting the transcription of MIR181A2HG and establishing a feedback loop driving lymphatic metastasis.
Conclusion
This study highlights the pivotal role of MIR181A2HG in GC progression and LNs metastasis. MIR181A2HG-based targeted therapy would represent a novel strategy for GC.
{"title":"The MIR181A2HG/miR-5680/VCAN-CD44 Axis Regulates Gastric Cancer Lymph Node Metastasis by Promoting M2 Macrophage Polarization","authors":"Weijie Zang, Yongpu Yang, Junjie Chen, Qinsheng Mao, Wanjiang Xue, Yilin Hu","doi":"10.1002/cam4.70600","DOIUrl":"10.1002/cam4.70600","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lymphatic metastasis in gastric cancer (GC) profoundly influences its prognosis, but the precise mechanism remains elusive. In this study, we identified the long noncoding RNA MIR181A2HG as being upregulated in GC and associated with LNs metastasis and prognosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The expression of MIR181A2HG in GC was identified through bioinformatics screening analysis and qRT-PCR validation. Both in vitro and in vivo functional studies revealed that MIR181A2HG facilitates lymphangiogenesis and lymphatic metastasis. Techniques such as immunofluorescence, immunohistochemistry, qRT-PCR, ELISA, CHIP, RNA-pulldown, luciferase reporter assay, and Co-IP were employed to investigate the mechanism of MIR181A2HG in LNs metastasis of GC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MIR181A2HG overexpressed in GC signifies an unfavorable prognosis and drives M2 polarization of TAMs enhancing lymphangiogenesis. Mechanistically, MIR181A2HG/miR-5680 axis as a novel ceRNA regulatory axis to upregulate versican (VCAN). On one hand, VCAN interacts with CD44 receptors on the surface of TAMs through paracrine secretion, promoting M2 macrophage polarization and subsequently enhancing the secretion of VEGF-C, ultimately facilitating lymphangiogenesis. On the other hand, VCAN binds to CD44 receptors on the surface of GC cells through autocrine secretion, activating the Hippo pathway and upregulating SP1, thereby promoting the transcription of MIR181A2HG and establishing a feedback loop driving lymphatic metastasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study highlights the pivotal role of MIR181A2HG in GC progression and LNs metastasis. MIR181A2HG-based targeted therapy would represent a novel strategy for GC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div> <section> <h3> Background</h3> <p>7-Hydroxymethotrexate (7-OHMTX) is the main metabolite in plasma following high-dose MTX (HD-MTX), which may result in activity and toxicity of the MTX. Moreover, 7-OHMTX could produce crystalline-like deposits within the renal tubules under acidic conditions or induce renal inflammation, oxidative stress, and cell apoptosis through various signaling pathways, ultimately leading to kidney damage. The objectives of this study were thus to explore the exposure–safety relationship of two compounds and search the most reliable marker for predicting HDMTX nephrotoxicity.</p> </section> <section> <h3> Method</h3> <p>A total of 280 plasma concentration data (140 for MTX and 140 for 7-OHMTX) for 60 pediatric patients with non-Hodgkin lymphoma (NHL) were prospectively collected. Plasma MTX and 7-OHMTX concentrations were determined using a high-performance liquid chromatography tandem mass spectrometry (HPLC–MS/MS) method. A nonlinear mixed effect model approach was used to build a joint population pharmacokinetic (PopPK) model. After validation, the model estimated the peak concentration (<i>C</i><sub>max</sub>) and area under the curve within the initial 48 h (AUC<sub>0-48h</sub>) of the patients after drug administration by Bayesian feedback. The receiver operating characteristic (ROC) curves were generated to identify an exposure threshold associated with nephrotoxicity.</p> </section> <section> <h3> Results</h3> <p>A three-compartment chain model (central and peripheral compartments for MTX and central compartment 7-OHMTX) with the first-order elimination adequately characterized the in vivo process of MTX and 7-OHMTX. The covariate analysis identified that the aspartate aminotransferase (AST) was strongly associated with the peripheral volume of distribution of MTX. Moreover, the <i>C</i><sub>max</sub> of MTX and 7-OHMTX showed significant differences (<i>p</i> < 0.0001, <i>p</i> = 0.0472, respectively) among patients with or without nephrotoxicity. Similarly, individuals with nephrotoxicity also exhibited substantially higher ratio of 7-OHMTX to MTX peak concentration and the sum of MTX + 2.25 times the concentration of 7-OHMTX (<i>p</i> < 0.0001, <i>p</i> = 0.0426, respectively). By ROC analysis, the <i>C</i><sub>max</sub> of MTX and 7-OHMTX had the greatest area under the curve (AUC) values (0.769 and 0.771, respectively). A <i>C</i><sub>max</sub> threshold of 9.26 μmol/L for MTX or a <i>C</i><sub>max</sub> threshold of 0.66 μmol/L for 7-OHMTX was associated with the best sensitivity/specificity for toxicity events (MTX: sensitivity = 0.886; specificity = 0.70; 7-OHMTX: sensitivity = 0.886; specificity
{"title":"Impact of Methotrexate and 7-Hydroxymethotrexate Exposure on Renal Toxicity in Pediatric Non-Hodgkin Lymphoma","authors":"Hao Bing, Yi Ma, Jiamin Xu, Qixian Ling, Yanlong Duan, Libo Zhao","doi":"10.1002/cam4.70516","DOIUrl":"10.1002/cam4.70516","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>7-Hydroxymethotrexate (7-OHMTX) is the main metabolite in plasma following high-dose MTX (HD-MTX), which may result in activity and toxicity of the MTX. Moreover, 7-OHMTX could produce crystalline-like deposits within the renal tubules under acidic conditions or induce renal inflammation, oxidative stress, and cell apoptosis through various signaling pathways, ultimately leading to kidney damage. The objectives of this study were thus to explore the exposure–safety relationship of two compounds and search the most reliable marker for predicting HDMTX nephrotoxicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>A total of 280 plasma concentration data (140 for MTX and 140 for 7-OHMTX) for 60 pediatric patients with non-Hodgkin lymphoma (NHL) were prospectively collected. Plasma MTX and 7-OHMTX concentrations were determined using a high-performance liquid chromatography tandem mass spectrometry (HPLC–MS/MS) method. A nonlinear mixed effect model approach was used to build a joint population pharmacokinetic (PopPK) model. After validation, the model estimated the peak concentration (<i>C</i><sub>max</sub>) and area under the curve within the initial 48 h (AUC<sub>0-48h</sub>) of the patients after drug administration by Bayesian feedback. The receiver operating characteristic (ROC) curves were generated to identify an exposure threshold associated with nephrotoxicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A three-compartment chain model (central and peripheral compartments for MTX and central compartment 7-OHMTX) with the first-order elimination adequately characterized the in vivo process of MTX and 7-OHMTX. The covariate analysis identified that the aspartate aminotransferase (AST) was strongly associated with the peripheral volume of distribution of MTX. Moreover, the <i>C</i><sub>max</sub> of MTX and 7-OHMTX showed significant differences (<i>p</i> < 0.0001, <i>p</i> = 0.0472, respectively) among patients with or without nephrotoxicity. Similarly, individuals with nephrotoxicity also exhibited substantially higher ratio of 7-OHMTX to MTX peak concentration and the sum of MTX + 2.25 times the concentration of 7-OHMTX (<i>p</i> < 0.0001, <i>p</i> = 0.0426, respectively). By ROC analysis, the <i>C</i><sub>max</sub> of MTX and 7-OHMTX had the greatest area under the curve (AUC) values (0.769 and 0.771, respectively). A <i>C</i><sub>max</sub> threshold of 9.26 μmol/L for MTX or a <i>C</i><sub>max</sub> threshold of 0.66 μmol/L for 7-OHMTX was associated with the best sensitivity/specificity for toxicity events (MTX: sensitivity = 0.886; specificity = 0.70; 7-OHMTX: sensitivity = 0.886; specificity ","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anoïsia Courtois, Sophie Gérard, Damien Esparteiro, Eric Nguyen-Khac, Ingrid Marcq, Grégory Fouquet
Background
Chronic and excessive alcohol consumption is the leading cause of death due to chronic liver disease. Alcohol-related liver disease (ALD) encompasses a broad spectrum of clinical and pathological features, ranging from asymptomatic and reversible pathologies to hepatocellular carcinoma (HCC), a highly prevalent and deadly liver cancer. Indeed, alcohol consumption is one of the main worldwide etiologies of HCC. However, the impact of alcohol consumption on HCC pathophysiology and the associated mechanisms remains unclear. Thus, in vitro alcohol-related HCC models are essential for addressing this issue and for assessing new molecular markers of this disease. In this review, we discuss the current in vitro models of alcohol-related HCC. Our global overview demonstrates the lack of uniformity regarding HCC cell lines, alcohol concentration, and duration of alcohol exposure among existing models. Despite efforts to model alcohol exposure effectively that demonstrate enhancement of cancer cell transformation markers and HCC aggressiveness following, respectively, short-term and long-term alcohol exposure, current in vitro models possess numerous limitations.
Aim
This review highlights future challenges in the development of more integrated and representative models of the complex pathophysiology of alcohol-related HCC.
{"title":"An Overview of In Vitro Models of Alcohol-Related Hepatocellular Carcinoma","authors":"Anoïsia Courtois, Sophie Gérard, Damien Esparteiro, Eric Nguyen-Khac, Ingrid Marcq, Grégory Fouquet","doi":"10.1002/cam4.70524","DOIUrl":"10.1002/cam4.70524","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic and excessive alcohol consumption is the leading cause of death due to chronic liver disease. Alcohol-related liver disease (ALD) encompasses a broad spectrum of clinical and pathological features, ranging from asymptomatic and reversible pathologies to hepatocellular carcinoma (HCC), a highly prevalent and deadly liver cancer. Indeed, alcohol consumption is one of the main worldwide etiologies of HCC. However, the impact of alcohol consumption on HCC pathophysiology and the associated mechanisms remains unclear. Thus, in vitro alcohol-related HCC models are essential for addressing this issue and for assessing new molecular markers of this disease. In this review, we discuss the current in vitro models of alcohol-related HCC. Our global overview demonstrates the lack of uniformity regarding HCC cell lines, alcohol concentration, and duration of alcohol exposure among existing models. Despite efforts to model alcohol exposure effectively that demonstrate enhancement of cancer cell transformation markers and HCC aggressiveness following, respectively, short-term and long-term alcohol exposure, current in vitro models possess numerous limitations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This review highlights future challenges in the development of more integrated and representative models of the complex pathophysiology of alcohol-related HCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lung adenocarcinoma (LUAD) exhibits molecular heterogeneity, with mitochondrial damage affecting progression. The relationship between mitochondrial damage and immune infiltration, and Weighted Gene Co-expression Network Analysis (WGCNA)-derived biomarkers for LUAD classification and prognosis, remains unexplored.
Aims
The objective of our research is to identify gene modules closely related to the clinical stages of LUAD using the WGCNA method. Based on the genes within these modules, we constructed machine learning (ML) models for classification and prognosis prediction, thereby facilitating precise diagnosis and personalized treatment of LUAD.
Materials & Methods
Using GeneCards and The Cancer Genome Atlas (TCGA) databases, we screened differentially expressed mitochondrial damage-related genes in LUAD. Immune cell infiltration patterns were assessed using Single-Sample Gene Set Enrichment Analysis (SSGSEA) method. Functional enrichment analyses were conducted to explore biological functions and signaling pathways. Gene modules related to clinical stages of LUAD were identified by WGCNA. ML models were constructed for classification and prognosis prediction, and validated in an independent Gene Expression Omnibus (GEO) dataset.
Results
The study revealed a significant relationship between mitochondrial damage and immune infiltration in LUAD. We identified a gene module closely associated with the clinical stages of LUAD. The ML models for classification and prognosis that were constructed demonstrated good effectiveness and generalization capabilities.
Discussion
Mitochondrial damage-related genes are crucial in LUAD progression and linked to immune infiltration. The gene module and models identified have potential applications in LUAD classification and prognosis, offering novel markers for precision medicine.
Conclusion
This study uncovers the relationship between mitochondrial damage and immune infiltration in LUAD, paving the way for molecular classification, prognosis prediction, and personalized treatment strategies.
背景：肺腺癌（LUAD）表现出分子异质性，线粒体损伤影响进展。线粒体损伤与免疫浸润之间的关系，以及加权基因共表达网络分析（WGCNA）衍生的LUAD分类和预后的生物标志物，仍未得到探索。目的：我们的研究目的是利用WGCNA方法识别与LUAD临床分期密切相关的基因模块。基于这些模块内的基因，我们构建了机器学习（ML）模型进行分类和预后预测，从而促进LUAD的精确诊断和个性化治疗。材料与方法：利用GeneCards和The Cancer Genome Atlas （TCGA）数据库，筛选LUAD中差异表达的线粒体损伤相关基因。采用单样本基因集富集分析（SSGSEA）方法评估免疫细胞浸润模式。通过功能富集分析来探索其生物学功能和信号通路。通过WGCNA鉴定与LUAD临床分期相关的基因模块。构建ML模型用于分类和预后预测，并在独立的Gene Expression Omnibus （GEO）数据集中进行验证。结果：研究显示LUAD患者线粒体损伤与免疫浸润有显著关系。我们发现了一个与LUAD临床分期密切相关的基因模块。所构建的机器学习分类和预后模型显示出良好的有效性和泛化能力。讨论：线粒体损伤相关基因在LUAD进展中至关重要，并与免疫浸润有关。所鉴定的基因模块和模型在LUAD的分类和预后中具有潜在的应用价值，为精准医疗提供了新的标志物。结论：本研究揭示了LUAD中线粒体损伤与免疫浸润的关系，为分子分类、预后预测和个性化治疗策略奠定了基础。
{"title":"Immunoinfiltration Analysis of Mitochondrial Damage-Related Genes in Lung Adenocarcinoma and Construction of a Classification and Prognostic Model Integrated With WGCNA and Machine Learning Algorithms","authors":"Jirong Zhang, Lin Lin","doi":"10.1002/cam4.70590","DOIUrl":"10.1002/cam4.70590","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lung adenocarcinoma (LUAD) exhibits molecular heterogeneity, with mitochondrial damage affecting progression. The relationship between mitochondrial damage and immune infiltration, and Weighted Gene Co-expression Network Analysis (WGCNA)-derived biomarkers for LUAD classification and prognosis, remains unexplored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The objective of our research is to identify gene modules closely related to the clinical stages of LUAD using the WGCNA method. Based on the genes within these modules, we constructed machine learning (ML) models for classification and prognosis prediction, thereby facilitating precise diagnosis and personalized treatment of LUAD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials & Methods</h3>\u0000 \u0000 <p>Using GeneCards and The Cancer Genome Atlas (TCGA) databases, we screened differentially expressed mitochondrial damage-related genes in LUAD. Immune cell infiltration patterns were assessed using Single-Sample Gene Set Enrichment Analysis (SSGSEA) method. Functional enrichment analyses were conducted to explore biological functions and signaling pathways. Gene modules related to clinical stages of LUAD were identified by WGCNA. ML models were constructed for classification and prognosis prediction, and validated in an independent Gene Expression Omnibus (GEO) dataset.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study revealed a significant relationship between mitochondrial damage and immune infiltration in LUAD. We identified a gene module closely associated with the clinical stages of LUAD. The ML models for classification and prognosis that were constructed demonstrated good effectiveness and generalization capabilities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Mitochondrial damage-related genes are crucial in LUAD progression and linked to immune infiltration. The gene module and models identified have potential applications in LUAD classification and prognosis, offering novel markers for precision medicine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study uncovers the relationship between mitochondrial damage and immune infiltration in LUAD, paving the way for molecular classification, prognosis prediction, and personalized treatment strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aims to elucidate the expression pattern of SERPINE1, assess its prognostic significance, and explore potential therapeutic drugs targeting this molecule.
Methods and Results
In this study, we delved into the variations in gene mutation, methylation patterns, and expression levels of SERPINE1 in head and neck squamous cell carcinoma (HNSCC) and normal tissues, leveraging comprehensive analyses of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. The connection between the biological function of the gene and prognosis was scrutinized through immune infiltration and enrichment analyses. Concurrently, we assessed the potential therapeutic value of SERPINE1 through drug sensitivity analysis. It was observed that, particularly in human papillomavirus (HPV) negative HNSCC, SERPINE1 exhibited elevated expression levels, correlating with poorer prognosis. The infiltration levels of eight cell types, such as eosinophils, Tgd, and macrophages, showed a positive correlation with SERPINE1 expression, whereas infiltration levels of four cell types, including cytotoxic cells, B cells, and pDCs, displayed a negative correlation. Furthermore, copy number variations of SERPINE1 were primarily characterized by homologous amplification, positively correlating with its expression, while methylation showed an inverse correlation. The outcomes of drug sensitivity analysis underscored the potential of SERPINE1 as a therapeutic target.
Conclusion
Elevated expression of SERPINE1 in HNSCC is intricately linked with adverse prognostic outcomes and has the potential to influence the immune microenvironment. Subsequent investigations are imperative to fully elucidate the prognostic implications of SERPINE1 as a biomarker and to unlock its therapeutic promise as a target for intervention.
{"title":"Prognostic Significance and Therapeutic Potential of SERPINE1 in Head and Neck Squamous Cell Carcinoma","authors":"Changyu Zhu, Heshu Liu, Zhixin Li, Yijun Shi, Jingyang Zhao, Yuping Bai, Qian Chen, Wei Li","doi":"10.1002/cam4.70605","DOIUrl":"10.1002/cam4.70605","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This study aims to elucidate the expression pattern of SERPINE1, assess its prognostic significance, and explore potential therapeutic drugs targeting this molecule.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>In this study, we delved into the variations in gene mutation, methylation patterns, and expression levels of SERPINE1 in head and neck squamous cell carcinoma (HNSCC) and normal tissues, leveraging comprehensive analyses of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. The connection between the biological function of the gene and prognosis was scrutinized through immune infiltration and enrichment analyses. Concurrently, we assessed the potential therapeutic value of SERPINE1 through drug sensitivity analysis. It was observed that, particularly in human papillomavirus (HPV) negative HNSCC, SERPINE1 exhibited elevated expression levels, correlating with poorer prognosis. The infiltration levels of eight cell types, such as eosinophils, Tgd, and macrophages, showed a positive correlation with SERPINE1 expression, whereas infiltration levels of four cell types, including cytotoxic cells, B cells, and pDCs, displayed a negative correlation. Furthermore, copy number variations of SERPINE1 were primarily characterized by homologous amplification, positively correlating with its expression, while methylation showed an inverse correlation. The outcomes of drug sensitivity analysis underscored the potential of SERPINE1 as a therapeutic target.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Elevated expression of SERPINE1 in HNSCC is intricately linked with adverse prognostic outcomes and has the potential to influence the immune microenvironment. Subsequent investigations are imperative to fully elucidate the prognostic implications of SERPINE1 as a biomarker and to unlock its therapeutic promise as a target for intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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