Journal of Cancer最新文献

{"title":"NAT10 Mediates <i>XPO1</i> mRNA N4-acetylation and Promotes Drug Resistance of Myeloma Cells.","authors":"Yinyin Xu, Li Wang, Christina He, Zhiqiang Liu, Rong Fu, Ying Xie","doi":"10.7150/jca.101403","DOIUrl":"https://doi.org/10.7150/jca.101403","url":null,"abstract":"<p><p>The eventually developed chemoresistance to proteasome inhibitors (PIs) is a major hurdle in curing patients with multiple myeloma (MM) and a key cause of poor prognosis, however the underlying molecular mechanisms of chemoresistance is still poorly understood. Herein, we provide evidences that N-acetyltransferase 10 (NAT10), a catalytic enzyme involving in the acetylation modification of RNA, is overexpressed in the BTZ-resistant (BR) MM cell lines and predicts poor outcomes in the clinic. Further manipulating of NAT10 gene expression in MM cells shows that enforced NAT10 expression decreases sensitivity to PI, however knockdown of NAT10 enhances anti-tumor efficacy of PIs in MM cells <i>in vitro</i> and <i>in vivo</i>. Acetylated RNA immunoprecipitation sequencing (acRIP-seq) combined with RIP-qPCR analysis identifies exportin 1 (XPO1) as an important downstream target of NAT10, with promotes N4-acetylcytidine (ac4C) modification of XPO1 mRNA. Importantly, expressions of XPO1 and NAT10 are meaningfully correlated in bone biopsies from the relapsed/refractory (R/R) MM patients, which were also highly associated with poor outcome. Translationally, dual pharmacological inhibition of NAT10 and XPO1 sensitizes MM cells to BTZ treatment in both cell lines and in a xenograft mouse model of MM. Thus, our study elucidates previously unrecognized role of ac4C modification of XPO1 mRNA in the chemoresistance of MM and provides a potential option for clinical management of R/R MM patients in the clinic.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL14 Induced N⁶-Methyladenosine Modification of FOXP4 mRNA in HBV-HCC.","authors":"Tian-Tian Wang, Yi-Mei Ji, Qian Zhang, Bo Liang, Ting-Ting Fan, Xin Ye","doi":"10.7150/jca.101385","DOIUrl":"https://doi.org/10.7150/jca.101385","url":null,"abstract":"<p><p>Chronic hepatitis B virus infections are a significant cause of liver cirrhosis and cancer. Our research reveals that HBV infection leads to a marked increase in m6A modification of Foxp4 mRNA, resulting in enhanced stability of the mRNA and a subsequent increase in Foxp4 mRNA levels. Analysis of biopsy samples from chronic HBV patients demonstrated consistent upregulation of m6A-modified Foxp4 mRNA levels alongside increased Foxp4 mRNA levels. Functionally, Foxp4 was found to promote proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells in laboratory settings. Additionally, HBV gene expression was shown to activate the PI3K/AKT pathway by modulating Foxp4 mRNA stability in HCC cells. This study provides valuable insights into the underlying mechanisms of HBV infection and its potential implications for cancer development.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Long-term Survival Risk Prediction Model for Patients with Superficial Esophageal Squamous Cell Carcinoma.","authors":"Ruoyun Yang, Min Wei, Xin Yu, Wei Su, Xiaoying Zhou, Han Chen, Guoxin Zhang","doi":"10.7150/jca.99042","DOIUrl":"https://doi.org/10.7150/jca.99042","url":null,"abstract":"<p><p><b>Objectives</b>: Given the data regarding the long-term prognosis of superficial esophageal squamous cell carcinoma (SESCC) is still lacking, we aimed to identify reliable prognostic factors and establish a high-precision prognosis model for patients with SESCC. <b>Methods</b>: A retrospective cohort study was conducted including patients with SESCC at a high-volume tertiary medical center. The primary outcome was disease-specific survival (DSS) at the end of follow-up (minimum of 29 months). Independent prognostic factors including innovative hematological and clinicopathological parameters were identified using comprehensive and novel statistical methods including best subset regression (BSR), the univariate and multivariate Cox analysis, lasso regression, and a dynamic nomogram model was established. <b>Results</b>: A total of 1,171 patients were finally enrolled. The median follow-up time is 83 months (range 29-149 months). Ten independent prognostic risk factors for a poor DSS were identified as follows: male (<i>P=</i>0.127), higher Charlson Comorbidity Index (CCI) (<i>P=</i>0.006), poorly differentiated tumor (<i>P</i><0.001), lymphovascular invasion (LVI) (<i>P</i><0.001), lymph node metastasis (LNM) (<i>P</i><0.001), additional treatment (<i>P</i>=0.007), neutrophils over 32.2x10⁹/L (<i>P</i>=0.003), red blood cell (RBC) lower than 4.45x10¹²/L (<i>P</i><0.001), hemoglobin (Hb) lower than or equal to 98 g/L (<i>P</i>=0.023), alpha-fetoprotein (AFP) higher than 3.24 ng/ml (<i>P</i>=0.034). Subsequently, an online dynamic nomogram was established <i>(https://yryouzu-tools.shinyapps.io/DynNomapp/)</i>. This prediction model showed favourable discrimination ability (area under the curve (AUC) was 0.913 (95% CI: 88.0 - 94.6) and a well-fitted calibration curve. <b>Conclusions</b>: We successfully established a long-term prognosis model for SESCC, which can be applied to effectively predict survival risks for patients, thus strengthening follow-up strategies.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Value of the Noble and Underwood Score in Patients with Non-Small Cell Lung Cancer Undergoing Surgical Resection.","authors":"Soomin An, Wankyu Eo, Dae Hyun Kim, Sookyung Lee","doi":"10.7150/jca.101320","DOIUrl":"https://doi.org/10.7150/jca.101320","url":null,"abstract":"<p><p><b>Background:</b> This retrospective study aimed to evaluate the clinical utility of the Noble and Underwood (NUn) score as a prognostic marker for overall survival (OS) in patients with stage I to IIIA non-small cell lung cancer (NSCLC). The NUn score is a novel composite marker that integrates C-reactive protein (CRP), serum albumin (ALB) levels, and white blood cell (WBC) count to provide a comprehensive assessment of systemic inflammation and nutritional status. <b>Methods:</b> We included patients with stage I to IIIA NSCLC and assessed the NUn score, calculated using CRP, ALB levels, and WBC count. Hazard ratios for OS were determined using Cox regression analysis. The predictive performance of the models was evaluated through metrics such as area under the curve (AUC), concordance index (C-index), integrated AUC (iAUC), integrated discrimination improvement (IDI), continuous net reclassification index (cNRI), and decision curve analysis (DCA). <b>Results:</b> The median age of the patients was 69 years, and 63.1% of patients were men. The cohort included 152 (63.1%) patients with stage I disease, 54 (22.4%) with stage II disease, and 35 (14.5%) with stage IIIA disease. In the multivariate Cox regression analysis, the NUn score, age, American Society of Anesthesiologists Physical Status, tumor-node-metastasis (TNM) stage, and pleural invasion emerged as independent prognostic factors for OS, forming the NUn model. The C-index and iAUC of the NUn model (0.832 and 0.802, respectively) outperformed those of the baseline model based solely on TNM stage. The NUn model also demonstrated superior discriminative capacity compared with the baseline model using metrics such as AUC, IDI, cNRI, and DCA at 3 and 5 years after surgery. Calibration of the nomogram based on the NUn model showed good accuracy. <b>Conclusions:</b> These findings underscore the prognostic significance of the NUn score in predicting OS among patients with stage I to IIIA NSCLC by integrating markers of inflammation and nutritional status. The NUn model, which integrates the NUn score with other clinical variables, exhibited superior discriminative ability compared with TNM stage alone. These findings highlight the potential of the NUn score as a valuable tool in personalized care for patients with NSCLC. Further external validation with independent cohorts is necessary to confirm the model's applicability to other populations.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DOK1 facilitates the advancement of ccRCC.","authors":"Wei Xie, Yuanfeng Zhang, Bian Shu, Zhechuan Zhang, Ronggui Zhang","doi":"10.7150/jca.104375","DOIUrl":"https://doi.org/10.7150/jca.104375","url":null,"abstract":"<p><p><b>Background:</b> Renal cell carcinoma (RCC) is one of the most common human cancers. Clear cell renal cell carcinoma (ccRCC) is a major subtype of RCC. However, the molecular mechanisms underlying ccRCC oncogenesis require further investigation. Docking protein 1 (DOK1) is a putative tumor suppressor gene; however, its role in ccRCC remains unclear. <b>Methods</b>: Bioinformatic analysis was used to illustrate the poor prognosis associated with DOK1 expression and its role in tumor development in ccRCC in patients. qPCR (quantitative polymerase chain reaction) and western blotting assays were used to validate DOK1 expression in ccRCC cells. <i>In vitro</i> experiments were performed to further elucidate the biological role of DOK1 in ccRCC. <b>Results:</b> DOK1 was overexpressed in ccRCC tissues and cells at both mRNA and protein levels. High DOK1 expression closely correlated with poor survival in patients with ccRCC. DOK1 expression significantly accelerated ccRCC proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Through PI3K (phosphatidylin-ositol-3-kinase)/AKT (protein kinase B)/GSK3β (glycogen synthase kinase 3 beta) signaling, DOK1 may control the progression of ccRCC. <b>Conclusion:</b> DOK1 has the potential to serve as a valuable biomarker and target for treatment in ccRCC through its regulation of PI3K/AKT/GSK3β signaling to promote ccRCC progression.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The lower incidence of cervical cancer in type 2 diabetes mellitus with sodium-glucose cotransporter 2 inhibitors utilization.","authors":"Tung-Lin Tsui, Yung-Chuan Ho, Kwo-Chang Ueng, Pei-Lun Liao, Jing-Yang Huang, Chia-Yi Lee, Shih-Chi Su, Shun-Fa Yang","doi":"10.7150/jca.101165","DOIUrl":"https://doi.org/10.7150/jca.101165","url":null,"abstract":"<p><p>Sodium-glucose cotransporter 2 (SGLT2) inhibitors are medications with anti-inflammatory effects used to treat type 2 diabetes mellitus (T2DM). Cervical cancer is the most common gynecological cancer and is characterized by elevated inflammatory status. Accordingly, this study aimed to investigate the potential association between SGLT2 inhibitor use and cervical cancer development. In this retrospective cohort study, female patients with T2DM were divided into 2 groups: SGLT2 inhibitor users and a control group of non-SGLT2 inhibitor users. After propensity score matching, the SGLT2 inhibitor group and control group each had 136 212 patients. Cox proportional hazards regression was conducted to obtain the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for cervical cancer between the 2 groups. Overall, 148 and 191 cases of cervical cancer were identified in the SGLT2 inhibitor and control groups, respectively. The incidence of cervical cancer was significantly lower in the SGLT2 inhibitor group than in the control group (aHR, 0.77; 95% CI, 0.62-0.96, <i>P</i> = 0.0179). In a subgroup analysis stratified by type of oral medication, the effect of SGLT2 inhibitors on cervical cancer development exhibited a significant difference compared with a biguanide group (aHR, 0.77; 95% CI, 0.63-0.95) and a sulfonylurea group (aHR, 0.69; 95% CI, 0.50-0.94) groups. In conclusion, the use of SGLT2 inhibitors in patients with T2DM is associated with reduced risk of cervical cancer development.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Survival Between Different Histological Subtypes in Cervical Cancer Patients: A Retrospective and Propensity Score-matched Analysis.","authors":"Yugu Zhang, Pei Shu, Xin Wang, Ganlu Ouyang, Jitao Zhou, Yaqin Zhao, Zhiping Li, Yongsheng Wang, Yalin Shen","doi":"10.7150/jca.100653","DOIUrl":"https://doi.org/10.7150/jca.100653","url":null,"abstract":"<p><p><b>Objective:</b> To investigate the correlation between different histological subtypes (adenosquamous carcinoma, adenocarcinoma, and squamous cell carcinoma) and the prognosis of cervical cancer. <b>Materials and Methods:</b> In this retrospective cohort analysis, patients with cervical cancer who underwent radical surgery followed by either concurrent chemoradiotherapy (CCRT) or radiotherapy (RT) at West China Hospital of Sichuan University between 2009 and 2018 were enrolled. The study included patients with confirmed pathological diagnoses of cervical adenosquamous carcinoma (ASC), adenocarcinoma (AC), and squamous cell carcinoma (SCC). To ensure a balanced representation, 1:3 propensity score matching (PSM) between cervical adenosquamous carcinoma (ASC) or adenocarcinoma (AC) and squamous cell carcinoma (SCC) was performed. The prognosis of different pathological subtypes, including 5-year overall survival (OS), 5-year disease-free survival (DFS), and treatment failure patterns in terms of recurrence and metastasis, were evaluated between groups. <b>Results:</b> This study enrolled a total of 714 patients between 2009 and 2018, of whom 614 (86%) were diagnosed with SCC. In a 1:3 ratio propensity score matching, 34 cases of ASC were matched with 102 cases of SCC, while 66 cases of AC were paired with another 198 cases of SCC. Baseline demographic and disease characteristics were well-balanced among the treatment groups. During a median follow-up period of 41 months (range: 14 to 122 months), a total of 40 patients experienced disease recurrence. The primary recurrence pattern was distant metastasis, observed in 36 out of 40 cases. Among these cases, recurrence occurred in 28 patients (9.3%) diagnosed with SCC, 10 patients (15.2%) with AC, and 2 patients (5.9%) with ASC. In the AC group, local failure and distant failure were observed in 2% and 12% of cases, respectively. In comparison, the corresponding rates in the paired SCC group were 0.6% and 8.7%. The 5-year OS and DFS rates in the AC group were 82.1% and 79.2%, respectively, compared to the paired SCC group, which had rates of 95.2% and 92.8% respectively (<i>p</i><0.05). Conversely, in the ASC group, the 5-year OS and DFS rates were 96.3% and 92.6%, while the paired SCC group displayed OS and DFS rates of 93.4% and 81.2% respectively, with no statistically significant difference observed. <b>Conclusions:</b> By comparing the prognostic outcomes of different histological subtypes, we concluded that AC histology was linked to a poor prognosis and an increased risk of distant recurrence. ASC histology had a similar outcome to SCC histology rather than AC. Given the poor prognosis for patients diagnosed with AC after adjusting for prognostic factors, it becomes imperative to explore alternative treatment options beyond the current conventional therapy for this condition.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the Secrets of Extracellular Vesicles: Orchestrating Tumor Microenvironment Dynamics in Metastasis, Drug Resistance, and Immune Evasion.","authors":"Rashid Mir, Sadaf Khursheed Baba, Imadeldin Elfaki, Naseh Algehainy, Mohammad A Alanazi, Faisal H Altemani, Faris Jamal Tayeb, Jameel Barnawi, Eram Husain, Ruqaiah I Bedaiwi, Ibrahim Altedlawi Albalawi, Muhanad Alhujaily, Mohammad Muzaffar Mir, Reema Almotairi, Hanan E Alatwi, Aziz Dhaher Albalawi","doi":"10.7150/jca.98426","DOIUrl":"https://doi.org/10.7150/jca.98426","url":null,"abstract":"<p><p>Extracellular vehicles (EVs) are gaining increasing recognition as central contributors to the intricate landscape of the tumor microenvironment (TME). This manuscript provides an extensive examination of the multifaceted roles played by EVs in shaping the TME, with a particular emphasis on their involvement in metastasis, drug resistance, and immune evasion. Metastasis, the process by which cancer cells disseminate to distant sites, remains a formidable challenge in cancer management. EVs, encompassing exosomes and microvesicles, have emerged as critical participants in this cascade of events. They facilitate the epithelial-to-mesenchymal transition (EMT), foster pre-metastatic niche establishment, and enhance the invasive potential of cancer cells. This manuscript delves into the intricate molecular mechanisms underpinning these processes, underscoring the therapeutic potential of targeting EVs to impede metastasis. Drug resistance represents a persistent impediment to successful cancer treatment. EVs are instrumental in intrinsic and acquired drug resistance, acting as mediators of intercellular communication. They ferry molecules like miRNAs and proteins, which confer resistance to conventional chemotherapy and targeted therapies. This manuscript scrutinizes the diverse strategies employed by EVs in propagating drug resistance while also considering innovative approaches involving EV-based drug delivery systems to counteract this phenomenon. Immune evasion is a hallmark of cancer, and EVs are central in sculpting the immunosuppressive milieu of the TME. Tumor-derived EVs thwart immune responses through various mechanisms, including T cell dysfunction induction, the expansion of regulatory T cells (Tregs), and polarization of macrophages towards an immunosuppressive phenotype. In addition, the manuscript explores the diagnostic potential of EVs as biomarkers and their role as therapeutic agents in immune checkpoint blockade therapies. This manuscript provides a comprehensive overview of EV's pivotal role in mediating intricate interactions within the TME, ultimately influencing cancer progression and therapeutic outcomes. A profound understanding of EV-mediated processes in metastasis, drug resistance, and immune evasion opens up promising avenues for developing innovative therapeutic strategies and identifying valuable biomarkers in the ongoing battle against cancer.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum CHI3L1 Levels Predict Overall Survival of Hepatocellular Carcinoma Patients after Hepatectomy.","authors":"Yanji Jiang, Wenfeng Gong, Yingchun Liu, Zihan Zhou, Xiumei Liang, Qiuling Lin, Moqin Qiu, Biaoyang Lin, Xiaoqiang Qiu, Hongping Yu","doi":"10.7150/jca.100791","DOIUrl":"https://doi.org/10.7150/jca.100791","url":null,"abstract":"<p><p><b>Objective:</b> The Chitinase 3-like protein 1 (CHI3L1) is currently used as a biomarker for the diagnosis of liver fibrosis. However, its prognostic value for hepatocellular carcinoma (HCC) patients remains controversial. In this study, we aimed to investigate the prognostic value of the CHI3L1 in HCC patients after hepatectomy. <b>Methods:</b> In total, 753 HCC patients who underwent curative hepatectomy between January 2017 to August 2021 were retrospectively recruited. The probability of overall survival (OS) was evaluated by the Kaplan-Meier method and compared between groups using the log-rank test. Cox proportional hazard regression analysis was used to determine the independent prognostic factors. A prognostic nomogram was constructed for further examine the clinical utility of CHI3L1 in HCC. <b>Results:</b> Kaplan-Meier analysis revealed that elevated serum CHI3L1 levels were associated with worse overall survival of HCC patients. Multivariate Cox regression analysis showed that the high-CHI3L1 group (≥198.94 ng/ml) was associated with a shorter survival time compared with that in the low-CHI3L1 group (< 198.94 ng/ml) after adjustment for potential confounding factors (HR =1.43, 95% CI = 1.05-1.94, <i>P</i> = 0.024). Additionally, the nomogram had sufficient calibration and discriminatory power in the training cohort, with C-indexes of 0.723 (95% CI: 0.673-0.772). The validation cohort showed similar results. Finally, we demonstrated that the AUC of the nomogram was 0.752 (95% CI: 0.683-0.821), which had better predictive ability than AFP (AUC: 0.644, 95% CI: 0.577-0.711). <b>Conclusion:</b> Our results confirmed that the CHI3L1 could serve as an independent predictor for OS in HCC patients after hepatectomy. The nomogram showed a good performance in prognosis prediction of HCC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Constructing a folate metabolism gene signature for predicting prognosis in pulmonary neuroendocrine carcinomas.","authors":"Quanying Tang, Luoyi Li, Ruiyao Wang, Xin Jin, Xuewang Jia, Yifan Zhu, Xiaoyue Sun, Jianguo Zhong, Huangsheng Xie, Yurong Da, Lingling Zu, Song Xu","doi":"10.7150/jca.102186","DOIUrl":"https://doi.org/10.7150/jca.102186","url":null,"abstract":"<p><p>Folate metabolism is a crucial biological process in cell proliferation and exhibits its pro-tumorigenic functions in multiple tumor types. However, its role in pulmonary neuroendocrine carcinomas remains uncertain. Folate metabolism related genes were obtained from previous studies, and the gene expression data and clinical data were collected from GEO database. The expression patterns of folate metabolism related genes were measured across normal and tumor tissues. We subsequently assessed their prognostic role using Kaplan-Meier and univariate Cox regression analysis. The core genes were isolated from 16 prognostic genes through four algorithms. Based on the expression of core genes, patients were divided into two clusters employing consensus clustering algorithm. Furthermore, we evaluated immune infltration level, biological mechanisms, and drug sensitivity. ALDH1L2 was finally identified through qRT-PCR and its pro-tumorigenic function was confirmed via <i>in vitro</i> experiments. The expression patterns of 26 folate metabolism related genes were evaluated between normal lung tissues and PNEC tumor tissues, and 20 of them exhibited differential expression. All of folate metabolism related genes were related to the prognosis of PNECS and 16 genes were identified as prognostic genes. Using SVM-RFE, RF, Xgboost and LASSO algorithm, three core genes were isolated from 16 prognostic genes. Based on the expression patterns of core genes, PNECs patients were divided into two clusters through consensus clustering algorithm. Cluster 1 was characterized by the worse survival, higher immune infiltration level, and sensitivity to chemotherapy. Compared with the HBEC cells, ALDH1L2 was notably overexpressed in NCI-H446 cells (SCLC cell line). ALDH1L2 knockdown significantly repressed the proliferation and migration capacity of tumor cells and increased the cell proportion in S phase. Our results indicated that folate metabolism gene signature is a reliable biomarker for PNECs. Classification based on this signature could be utilized to guide the treatment of PNECs patients and improve its prognosis.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}