World Journal of Oncology最新文献

{"title":"Analysis of Pancreatic Cancer Genetic Risk Factors in a Multi-Ethnic Population Sample.","authors":"Abdullah Al-Qahtani, Ali Al-Ali, Bency John, Kusum Kapila, Rabeah Al-Temaimi","doi":"10.14740/wjon1911","DOIUrl":"https://doi.org/10.14740/wjon1911","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer (PC) has one of the highest mortality to incidence ratio of all cancers. Early identification of at-risk individuals should permit early diagnosis. Genome-wide association studies showed the association of several genetic variants with PC risk in multi-ethnic populations. Our objective was to examine the association of these genetic variants with PC in a population sample from Kuwait.</p><p><strong>Methods: </strong>DNA samples from 103 pancreatic ductal adenocarcinoma (PDAC) specimens and 132 healthy controls were used for genotyping <i>ABO</i> rs505922, <i>BCAR1</i> rs7190458, <i>LINC-PINT</i> rs6971499, <i>HNF1B</i> rs4795218, <i>VDR</i> rs2228570 rs731236, and <i>PRSS1</i> rs111033565 rs111033568 rs387906698 and rs267606982 using TaqMan genotyping assays, and VDR expression was performed by immunocytochemistry.</p><p><strong>Results: </strong><i>ABO</i> rs505922C and <i>VDR</i> rs2228570A were associated with PDAC risk (odds ratio (OR): 1.55, 95% confidence interval (CI): 1.07 - 2.24, P = 0.027; OR: 1.64, 95% CI: 1.09 - 2.48, P = 0.024; respectively). An unweighted polygenic risk score (<i>ABO</i> rs505922, <i>BCAR1</i> rs7190458, <i>LINC-PINT</i> rs6971499, and <i>HNF1B</i> rs4795218) was significantly associated with PDAC risk (β: -0.11, 95% CI: -0.15 to -0.05, P < 0.001). VDR expression was downregulated or absent in most PDAC specimens regardless of <i>VDR</i> haplotype.</p><p><strong>Conclusion: </strong><i>ABO</i> rs505922C and <i>VDR</i> rs2228570A are PDAC genetic risk factors in our population. Ethnicity influences the association of reported genetic PDAC risk factors and should be adjusted for when performing PDAC genetic risk estimations. Investigation of these genetic risk factors in other ethnic populations is a necessity to evaluate their PDAC risk prediction potential.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142336800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of Five-Year Relative Survival of Patients With Endometrial Cancer: A Period Analysis.","authors":"Xiao Jiao Zhao, Xin Bing, Qi Qi Lei, Yong Ran Cheng, Jun Yang, Liang You Wang, Tian Hua Chen, Tian Hui Chen","doi":"10.14740/wjon1921","DOIUrl":"https://doi.org/10.14740/wjon1921","url":null,"abstract":"<p><strong>Background: </strong>Endometrial cancer is one of the most common female cancers globally and in China. Although timely assessment of 5-year relative survival is crucial for guiding secondary prevention and early screening programs for endometrial cancer patients, those kinds of data are scarce in China. We aimed to provide a timely and accurate assessment of 5-year relative survival for patients with endometrial cancer from eastern China.</p><p><strong>Methods: </strong>Overall, 945 patients diagnosed with endometrial cancer during 2004 - 2018 from four cancer registries with high-quality data from Taizhou, eastern China were included. Period analysis was used to calculate 5-year relative survival for overall and the stratification by age at diagnosis and region. Model-based period analysis was used to predict the 5-year relative survival for the upcoming period of 2019 - 2023.</p><p><strong>Results: </strong>We found that 5-year relative survival during 2014 - 2018 reached 86.4% for overall, while urban areas had higher survival compared to rural areas (91.3% vs. 85.3%). Furthermore, there was a clear age gradient, decreasing from 89.3% for age < 55 years to 80.5% for age > 74 years. Predicted 5-year relative survival for the upcoming period 2019 - 2023 could reach 88.4%.</p><p><strong>Conclusions: </strong>We provide, a timely and accurate assessment of 5-year relative survival for patients with endometrial cancer from Taizhou, eastern China, reaching 86.4% for overall. Our finding has important implications for the overall evaluation of early detection and screening programs for patients with endometrial cancer in eastern China.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142336801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patterns and Frequency of Pathogenic Germline Variants Among Prostate Cancer Patients Utilizing Multi-Gene Panel Genetic Testing.","authors":"Ramiz Abu Hijlih, Baha Sharaf, Samer Salah, Hira Bani Hani, Sarah M Nielsen, Brandie Heald, Edward D Esplin, Rami Ghanem, Abdulla Alzibdeh, Tamer Al-Batsh, Yosra Al-Masri, Hikmat Abdel-Razeq","doi":"10.14740/wjon1896","DOIUrl":"https://doi.org/10.14740/wjon1896","url":null,"abstract":"<p><strong>Background: </strong>Germline genetic testing (GGT) has significant implications in the management of patients with prostate cancer (PCa). Herein, we report on patterns and frequency of pathogenic/likely pathogenic germline variants (P/LPGVs) among newly diagnosed Arab patients with PCa.</p><p><strong>Methods: </strong>Patients meeting the National Comprehensive Cancer Network (NCCN) eligibility criteria for GGT were offered a 19-gene PCa panel or an expanded 84-gene multi-cancer panel.</p><p><strong>Results: </strong>During the study period, 231 patients were enrolled; 107 (46.3%) had metastatic disease at diagnosis. In total, 17 P/LPGVs were detected in 17 patients (7.4%). Among the 113 (48.9%) patients who underwent GGT with the 19-gene panel, eight (7.1%) had P/LPGVs, compared to nine (7.6%) of the 118 (51.1%) who did GGT through the expanded 84-gene panel (P = 0.88). Variant of uncertain significance (VUS) rate was higher (n = 73, 61.9%) among the group who underwent expanded 84-gene panel testing compared to those who underwent the 19-gene PCa panel (n = 35, 30.9%) (P = 0.001). P/LPGVs in DNA damage repair (DDR) genes, most frequently <i>BRCA2</i>, <i>CHEK2</i> and <i>TP53</i>, were the most common P/LPGVs findings.</p><p><strong>Conclusion: </strong>This study is the first to characterize the germline genetic profile of an Arab population with PCa. All detected P/LPGVs were potentially actionable, with most variants able to be detected with a PCa-specific panel.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142336806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Vitamin C Intake Is Associated With Decreased Pancreatic Cancer Risk.","authors":"Maria Pereira, Matthew Cardeiro, Lexi Frankel, Bryan Greenfield, Kazuaki Takabe, Omar M Rashid","doi":"10.14740/wjon1854","DOIUrl":"10.14740/wjon1854","url":null,"abstract":"<p><strong>Background: </strong>Patients with pancreatic cancer have an unfavorable 5-year survival rate of approximately 3% due to diagnosis occurring at advanced stages. Prior research has proposed vitamin C may have a therapeutic and preventative role in pancreatic cancer.</p><p><strong>Methods: </strong>A Health Insurance Portability and Accountability Act (HIPAA) compliant national database was utilized to assess pancreatic cancer risk in patients with or without a history of vitamin C intake. The International Classification of Diseases (ICD) codes were used, specifically the International Classification of Diseases, 10th Edition (ICD-10) and International Classification of Diseases, Nineth Edition (ICD-9), between January 2010 and December 2020. Patients were matched, and statistical analyses were implemented. Chi-squared, logistic regression, and odds ratio were used to test for significance and to estimate relative risk.</p><p><strong>Results: </strong>A total of 83,941 patients were identified as utilizing prescribed vitamin C. Subsequent matching by Charlson Comorbidity Index (CCI) score and age resulted in two groups of 50,384 patients. The incidence of pancreatic cancer was 243 (0.48%) in the group with a history of vitamin C intake compared to 442 (0.88%) in the control group. The difference was statistically significant by P < 3.174 × 10^-14 with an odds ratio of 0.548 (95% confidence interval (CI): 0.468 - 0.641). Overall, patients without vitamin C prescription had an increased prevalence of pancreatic cancer throughout all ages and regions of the United States when compared to those with a vitamin C prescription. In addition, healthcare costs were higher in total for the control group when compared to the experimental group.</p><p><strong>Conclusions: </strong>This retrospective cohort study found a statistically significant correlation between vitamin C and subsequent incidence of pancreatic cancer. Further studies are recommended to explore vitamin C's redox and cofactor activity in the context of preventing and possibly treating pancreatic cancer, as well as consider pancreatic cancer lifestyle risk factors such as smoking.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11236377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Outcomes Between Partial and Radical Laparoscopic Nephrectomy for Localized Renal Tumors Larger Than Four Centimeters: A Systematic Review and Meta-Analysis.","authors":"Bao Nan Dong, Jie Song, Wen Li Yang, Hui Zhan, Ting Luan, Jian Song Wang","doi":"10.14740/wjon1866","DOIUrl":"10.14740/wjon1866","url":null,"abstract":"<p><strong>Background: </strong>Earlier studies have juxtaposed different laparoscopic methods for treating renal tumors; however, extensive evidence with a particular focus on large kidney tumors remains lacking. The objective of this meta-analysis was to assess the perioperative outcomes, kidney performance, and cancer-related results of laparoscopic partial nephrectomy (LPN) versus laparoscopic radical nephrectomy (LRN) for treating extensive, localized, non-metastatic kidney tumors (cT1b-cT2N0M0).</p><p><strong>Methods: </strong>We systematically searched multiple databases from database inception until December 2023 for relevant studies. Selected data were analyzed with the Cochrane Collaboration's Review Manager 5.4 software using a random-effects model. Outcomes were expressed as odds ratios and weighted mean differences with 95% confidence intervals, considering a P value of < 0.05 as significant.</p><p><strong>Results: </strong>Data from nine studies encompassing 1,303 patients (529 LPN, 774 LRN) revealed that LPN was associated with lengthier surgeries and increased blood loss compared to LRN. While LPN exhibited higher postoperative complication rates, the disparity did not reach statistical significance. LPN led to improved postoperative renal function, manifesting as a reduced estimated glomerular filtration rate (eGFR) decline and fewer incidents of new chronic kidney disease cases. Both groups demonstrated comparable tumor recurrence and overall mortality rates, but LPN exhibited significantly lower cancer-specific mortality rates.</p><p><strong>Conclusions: </strong>LPN, despite longer operative times and greater intraoperative blood loss, was found to be superior to LRN in preserving postoperative renal function. Oncologically, LPN and LRN have comparable overall mortality rates, but LPN showed a significant advantage in terms of lower cancer-specific mortality rates.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11236382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of Period Analysis to Timely Assess Five-Year Relative Survival for the Patients With Bone Cancer.","authors":"Xian Kuan Xie, Xiao Jiao Zhao, Run Hua Li, Yong Ran Cheng, Xin Bing, Jun Yang, Liang You Wang, Hui Jun Zhu, Tian Hui Chen, Jin Fei Chen","doi":"10.14740/wjon1875","DOIUrl":"10.14740/wjon1875","url":null,"abstract":"<p><strong>Background: </strong>While timely assessment of long-term survival for patients with bone cancer is essential for evaluation on early detection and prognosis level of treatment of bone cancer, those data are extremely scarce in China. We aimed to timely and accurately assess long-term survival for patients with bone cancer in Eastern China.</p><p><strong>Methods: </strong>Patients diagnosed with bone cancer during 2004 - 2018 from four cancer registries with high-quality data from Taizhou, Eastern China were included. Five-year relative survival (RS) of bone cancer patients was calculated by period analysis for overall and the stratification. We further predicted 5-year RS during upcoming 2019 - 2023 using a model-based period analysis and survival data during 2004 - 2018.</p><p><strong>Results: </strong>Overall, 5-year RS for patients with bone cancer during 2014 - 2018 reached 46.6%, being 40.8% for male and 51.0% for female. Five-year RS declined along with aging, decreasing from 58.9% for age < 45 years to 41.5% for age > 60 years, while 5-year RS for urban area was higher compared to rural area (59.1% vs. 44.3%). The 5-year RS during upcoming 2019 - 2023 reached 48.3%. We found a clear upward trend in 5-year RS during 2004 - 2023 for overall and the stratification by sex, age at diagnosis, and region.</p><p><strong>Conclusions: </strong>We found that, for first time in China using period analysis, most up-to-date 5-year RS for patients with bone cancer reached 46.6% during 2014 - 2018, and is projected to reach 48.3% for the period 2019 - 2023, which has important implications for timely evaluation on early detection and prognosis level of treatment for patients with bone cancer in Eastern China.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11236380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Opportunities and Challenges in the Development of Antibody-Drug Conjugate for Triple-Negative Breast Cancer: The Diverse Choices and Changing Needs.","authors":"Qi Tang, Hui Li, Xin Tong Zhao, Ze Ying Li, Chun Xiao Ma, Shao Qiang Zhou, De Dian Chen","doi":"10.14740/wjon1853","DOIUrl":"10.14740/wjon1853","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is a highly heterogeneous breast cancer subtype, which is also characterized by the aggressive phenotype, high recurrence rate, and poor prognosis. Antibody-drug conjugate (ADC) is a monoclonal antibody with a cytotoxic payload connected by a linker. ADC is gaining more and more attention as a targeted anti-cancer agent. Clinical studies of emerging ADC drugs such as sacituzumab govitecan and trastuzumab deruxtecan in patients with metastatic breast cancer (including TNBC) are progressing rapidly. In view of its excellent clinical efficacy and good tolerability, Sacituzumab govitecan gained accelerated approval by the FDA for the treatment of advanced metastatic TNBC in 2020. This review discusses the treatment status and challenges in TNBC, with an emphasis on the current status of ADC development and clinical trials in TNBC and metastatic breast cancer. We also summarize the clinical experience and future exploration directions of ADC development for TNBC patients.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11236369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proximal Femoral Metastasis From Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma Mimicking Osteosarcoma on Magnetic Resonance Imaging.","authors":"Chang Jun Chen, Jun Feng Yin, Hao Xuan Zhang, Qing Wei Ma, Xin Zhao, Meng Chen, Da Yong Peng","doi":"10.14740/wjon1888","DOIUrl":"10.14740/wjon1888","url":null,"abstract":"<p><p>The aggressive nature of lung cancer is frequently accompanied by a high incidence of bone metastasis; however, proximal femoral metastasis from lung cancer is comparatively uncommon when compared to other malignancies. In this report, we present the case of a 53-year-old Asian male who presented with pain in the left thigh and back. Magnetic resonance imaging revealed severe bone destruction with involvement of adjacent soft tissue mass at the left thigh, exhibiting imaging findings that mimic osteosarcoma. Subsequent bone biopsy confirmed the diagnosis of epidermal growth factor receptor (<i>EGFR</i>)-mutated lung adenocarcinoma with bone metastasis. The patient achieved survival following administration of osimertinib and underwent surgery for femoral metastases without palliative surgery for lung cancer. Therefore, proximal femoral metastasis from <i>EGFR</i>-mutated lung adenocarcinoma should be considered as a differential diagnosis in patients suspected to have osteosarcoma. The imaging findings of proximal femoral metastasis from <i>EGFR</i>-mutated lung adenocarcinoma were presented, and their therapeutic management was discussed.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11236371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Results of Stereotactic Body Radiotherapy With CyberKnife-M6 for Primary and Metastatic Lung Cancer.","authors":"Sureyya Sarihan, Sema Gozcu Tunc, Zenciye Kiray Irem, Arda Kahraman, Gokhan Ocakoglu","doi":"10.14740/wjon1865","DOIUrl":"10.14740/wjon1865","url":null,"abstract":"<p><strong>Background: </strong>The aim of the study was to evaluate the efficacy of stereotactic body radiotherapy (SBRT) using the CyberKnife-M6 (CK-M6) with lung optimized treatment (LOT) module in patients with primary lung cancer and lung metastases.</p><p><strong>Methods: </strong>Forty-two lesions from 35 patients were treated between 2019 and 2022. Four-dimensional computed tomography images were obtained when the patients were in a free breathing modality. Tracking modality was selected prospectively according to the visibility of the target. The median prescribed dose was 48 Gy in four fractions (fx) (28 - 55 Gy/1- 7 fx). The median age was 68 years (47 - 82 years), and 43% of cases were adenocarcinoma. The median lesion size was 15 mm (6 - 36 mm).</p><p><strong>Results: </strong>Complete, partial and stable responses were obtained as 26%, 62%, and 9.5% at a median of 2 months (1 - 6 months), and 35.5%, 47.5% and 5% at the 12th month evaluation, respectively. Grade 3 and higher toxicity was not observed in any case. The mean and 2-year overall survival (OS) was 31.5 months and 54%, and the local recurrence-free survival (LRFS) was 29.6 months and 51%, respectively. In univariate analysis, target lesion type, complete response (CR), and higher esophagus maximum dose were favorable factors for OS and LRFS (P < 0.05). The CR at 12th month evaluation remained significant in multivariate analysis in terms of OS (hazard ratio = 8.602, 95% confidence interval: 1.05 - 70.01; P = 0.044).</p><p><strong>Conclusions: </strong>A mean LRFS of 29.6 months and OS of 31.5 months were obtained in patients with primary and metastatic lung cancer. With a median treatment time of 25 min, motion-managed strategy with CK-M6-LOT-based SBRT is an effective, safe, and comfortable treatment method for lung cancer.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11236372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Significance and Possible Biological Mechanism for <i>CLDN8</i> Downregulation in Kidney Renal Clear Cell Carcinoma Tissues.","authors":"Han Chu Ji, Jian Di Li, Guan Lan Zhang, Zhi Guang Huang, Ji Wen Cheng, Sheng Hua Li, Chun Yan Zhao, Yu Xing Tang, Kai Qin, You Liang Ma, Yu Long, Gang Chen, Bin Qin","doi":"10.14740/wjon1869","DOIUrl":"10.14740/wjon1869","url":null,"abstract":"<p><strong>Background: </strong>The clinical role of claudin 8 (<i>CLDN8</i>) in kidney renal clear cell carcinoma (KIRC) remains unclarified. Herein, the expression level and potential molecular mechanisms of <i>CLDN8</i> underlying KIRC were determined.</p><p><strong>Methods: </strong>High-throughput datasets of KIRC were collected from GEO, ArrayExpress, SRA, and TCGA databases to determine the mRNA expression level of the <i>CLDN8</i>. In-house tissue microarrays and immunochemistry were performed to examine CLDN8 protein expression. A summary receiver operating characteristic curve (SROC) and standardized mean difference (SMD) forest plot were generated using Stata v16.0. Single-cell analysis was conducted to further prove the expression level of <i>CLDN8</i>. A clustered regularly interspaced short palindromic repeats knockout screen analysis was executed to assess the growth impact of <i>CLDN8</i>. Functional enrichment analysis was conducted using the Metascape database. Additionally, single-sample gene set enrichment analysis was implied to explore immune cell infiltration in KIRC.</p><p><strong>Results: </strong>A total of 17 mRNA datasets comprising 1,060 KIRC samples and 452 non-cancerous control samples were included in this study. Additionally, 105 KIRC and 16 non-KIRC tissues were analyzed using in-house immunohistochemistry. The combined SMD was -5.25 (95% confidence interval (CI): -6.13 to -4.37), and CLDN8 downregulation yielded an SROC area under the curve (AUC) close to 1.00 (95% CI: 0.99 - 1.00). <i>CLDN8</i> downregulation was also confirmed at the single-cell level. Knocking out <i>CLDN8</i> stimulated KIRC cell proliferation. Lower <i>CLDN8</i> expression was correlated with worse overall survival of KIRC patients (hazard ratio of <i>CLDN8</i> downregulation = 1.69, 95% CI: 1.2 - 2.4). Functional pathways associated with <i>CLDN8</i> co-expressed genes were centered on carbon metabolism obstruction, with key hub genes <i>ACADM</i>, <i>ACO2</i>, <i>NDUFS1</i>, <i>PDHB</i>, <i>SDHD</i>, <i>SUCLA2</i>, <i>SUCLG1</i>, and <i>SUCLG2.</i></p><p><strong>Conclusions: </strong><i>CLDN8</i> is downregulated in KIRC and is considered a potential tumor suppressor. <i>CLDN8</i> deficiency may promote the initiation and progression of KIRC, potentially in conjunction with metabolic dysfunction.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11236366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}