Journal of Cancer最新文献

{"title":"Integrated machine learning based on cuproptosis and RNA methylation regulators to explore the molecular model of prostate cancer and provide novel insights to immunotherapy.","authors":"Junchao Wu, Wentian Wu, Jiaxuan Qin, Ziqi Chen, Rongfang Zhong, Xunkai Zhu, Jialin Meng, Peng Guo, Song Fan","doi":"10.7150/jca.112843","DOIUrl":"10.7150/jca.112843","url":null,"abstract":"<p><p><b>Background:</b> As a highly prevalent tumor in males, prostate cancer (PCa) needs newly developed biomarkers to guide prognosis and treatment. However, few researches have elaborated on the function of cuproptosis-associated RNA methylation regulators (CARMRs). <b>Methods:</b> We identified CARMRs based on single-sample gene set enrichment analysis and weighted gene co-expression network analyses. Subsequently, we performed 10 machine learning algorithms and 101 combinations of them to select the best model in TCGA, GSE70768, GSE70769, and DKFZ cohorts. Furthermore, we explored the potential function of CARMRs in the tumor microenvironment, immunotherapy, and tumor mutation burden (TMB). We validated the expression of the two genes with the largest regression coefficients using qRT-PCR. <b>Results:</b> In our analysis, we successfully established a consensus prognostic model with 9 CARMRs based on the 101-machine learning framework. Furthermore, functional enrichment analysis revealed different metabolic and signaling pathways in the high- and low-risk groups. Notably, the high-risk group had a higher TMB, a lower level of immune infiltration, and a lower expression of immune checkpoints. Through drug sensitive analysis, we screened chemotherapy drugs suitable for different groups. Vitro experiments illustrated the high expression of C4orf48 and SLC26A1 in PCa compared with normal controls. The discovery was in concordance with bioinformatic analysis results. <b>Conclusion:</b> A gene signature with 9 CARMRs was developed in our study, which served as biomarkers for PCa. This brings benefits in determining the prognosis of patients with PCa and guiding personalized treatment.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2762-2777"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325854","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":"TACE Empowers Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors in Unresectable HCC: A Multicenter Retrospective Study.","authors":"Yu Lei, Yaowei Bai, Xiatong Bai, Jiacheng Liu, Bo Sun, Wenlong Wu, Xiaoling Zhi, Yang Su, Hongsen Zhang, Chuansheng Zheng","doi":"10.7150/jca.112706","DOIUrl":"10.7150/jca.112706","url":null,"abstract":"<p><p><b>Purpose</b>: The aim of this multicenter retrospective study was to evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) in treating advanced hepatocellular carcinoma (HCC) compared to treatment with TKI and ICI alone. <b>Methods</b>: The study included 286 patients with advanced HCC, of which 210 were treated with TACE, TKI, and ICI (TACE+T+I group) and 76 with TKI and ICI alone (T+I group). Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and disease control rate (DCR) were assessed. A nomogram was developed to stratify patients into high-risk and low-risk groups based on their one-year and two-year survival probabilities. <b>Results</b>: Patients in the TACE+T+I group demonstrated significantly longer PFS (8.4 months vs. 4.0 months, Log-rank <i>P</i> = 0.0016) and median OS (14.5 months vs. 10.0 months, Log-rank <i>P</i> < 0.0001) compared to the T+I group. Additionally, the TACE+T+I group had a higher ORR (56.7% vs. 21.1%, <i>P</i> = 0.002) and DCR (84.3% vs. 72.4%, <i>P</i> = 0.023). Both groups exhibited good tolerance to adverse events. A nomogram incorporating factors such as therapeutic strategy, prothrombin time (PT), age, and tumor size effectively categorized patients into low- and high-risk groups with notably different survival outcomes. <b>Conclusion</b>: These findings suggest that TACE combined with TKI and ICI significantly improved survival outcomes and showed good safety compared to TKI and ICI alone in the treatment of advanced HCC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2750-2761"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325857","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":"Stanniocalcin-2 significantly promotes colorectal cancer progression by regulating cancer cell proliferation and invasion.","authors":"Fang Li, Zihao Liu, Kaibin Huang, Shunkai Ding, Chang Zhu, Yuxiang Fu, Xiao Sun, Shipai Zhang, Rui Zhang, Zhipeng Jiang, Keli Zhong, Qijun Zheng","doi":"10.7150/jca.101892","DOIUrl":"10.7150/jca.101892","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Our study delves into the molecular intricacies of CRC by analyzing gene expression profiles across multiple datasets, revealing significant gene alterations that distinguish CRC from normal tissues. We identified Stanniocalcin-2 (STC2) as a key regulator in CRC, associated with poor prognosis, survival outcomes and cancer cell proliferation or invasion. Through comprehensive data mining of the Gene Expression Omnibus (GEO), the European Bioinformatics Institute (EMBL-EBI), and The Cancer Genome Atlas (TCGA), we emphasized the role of STC2 in tumorigenesis. Our pan-cancer analysis established STC2's involvement in various cancer types, underscoring its potential as a universal biomarker. Additionally, we performed experimental research and found STC2 is significantly upregulated in CRC tissue and can promote CRC progression by regulating cancer cell invasion and proliferation. This study provides valuable insights into the oncogenic role of STC2, proposing it as a promising target for therapeutic intervention and a marker for aggressive cancer phenotypes.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2737-2749"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325856","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":"Pan-cancer analysis identifies DBF4B as an immunologic and prognostic biomarker.","authors":"Chongjiu Qin, Yu Chen, Haifei Qin, Xinlei Huang, Haixiang Xie, Kejian Yang, Junqi Liu, Xin Zhou, Xiwen Liao, Chuangye Han, Hao Su, Guohong Yan, Zuying Wan, Tao Peng, Guangzhi Zhu","doi":"10.7150/jca.109134","DOIUrl":"10.7150/jca.109134","url":null,"abstract":"<p><p>DBF4 zinc finger B (DBF4B) is a regulator of cellular CDC7 proteins, and the complex it forms with CDC7 proteins plays a key role in coordinating the initiation of DNA replication. Compared with previous DBF4B studies, this study is the first to use a publicly available database to explore DBF4B differential expression and prognosis in different cancers, as well as its association with gene mutations, molecular and immune subtypes, immune infiltration, methylation, and drug sensitivity. Our results showed that DBF4B was significantly differentially expressed in most cancer types as well as in cancers with different molecular and immune subtypes, and DBF4B was also significantly correlated with the prognosis of a subset of cancers. Furthermore, our analysis showed that DBF4B expression in liver hepatocellular carcinoma (LIHC) was associated with a variety of factors, including age, gender, race, height, weight, body mass index (BMI), presence of residual tumor, and tumor status. Elevated DBF4B expression was correlated with poorer overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). especially in different clinical subtypes. In conclusion, DBF4B may be a key molecular biomarker for pan-cancer immunology and prognosis and an independent prognostic risk factor for LIHC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2626-2648"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325868","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":"Current status and future prospects of cancer-derived immunoglobulins in pancreatic cancer.","authors":"Rui Ma, Fusheng Zhang, Yongsu Ma, Weikang Liu, Guangnian Liu, Yiran Chen, Jixin Zhang, Yinmo Yang, Xiaodong Tian","doi":"10.7150/jca.109497","DOIUrl":"10.7150/jca.109497","url":null,"abstract":"<p><p>Immunoglobulin (Ig) is an important part of the immune system, which is mainly produced by B cells to recognize and kill pathogens. In recent years, the concept of cancer-derived immunoglobulin (cIg) has been proposed. cIg is a special form of Ig found in tumor microenvironment, and the role of cIg in tumor development and potential clinical significance of cIg have attracted more attention recently. The discovery of cIg marks a new understanding of tumor immune response and provides new ideas for early diagnosis and individualized treatment of tumors. Pancreatic cancer is a highly malignant tumor that does not respond well to conventional treatment, and causes serious complications such as pancreatic cancer-associated diabetes. Therefore, exploring potential role of cIg in pancreatic cancer and the progression of pancreatic cancer-associated diabetes is expected to be a breakthrough to improve the diagnosis and treatment of pancreatic cancer and associated complications. This review aims to summarize current research status of cIg in the field of pancreatic cancer, and provide new ideas for modulating microenvironment of pancreatic cancer to improve diagnostic efficiency and therapeutic effect.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2673-2679"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325848","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":"Two-Sample Network Mendelian Randomization and Single-Cell Analysis Reveal the Causal Associations and Underlying Mechanisms Between Antihypertensive Drugs and Kidney Cancer.","authors":"Ruiyi Deng, Mingrui Zou, Jianhui Qiu, Jiaheng Shang, Chaojian Yu, Peidong Tian, Yizhou Wang, Lin Cai, Jingcheng Zhou, Kan Gong","doi":"10.7150/jca.110850","DOIUrl":"10.7150/jca.110850","url":null,"abstract":"<p><p><b>Background</b>: Antihypertensive drugs represent the most widely used drugs worldwide. However, the association between antihypertensive drugs and the risk of kidney cancer remains unclear. This study innovatively integrates multi-omics and causal inference approaches to investigate the long-term effects and potential mechanisms of 12 antihypertensive drug classes on kidney cancer risk. <b>Methods:</b> In this study, novel approaches including two-sample mendelian randomization (MR), summary-data-based mendelian randomization (SMR), two-step network MR, and single-cell transcriptomic analysis were employed. Single nucleotide polymorphisms (SNPs) were obtained from genome-wide association studies (GWASs) to proxy exposures and outcomes. The cis-expression quantitative trait loci (cis-eQTL) as the proxies of exposure were also obtained. MR estimates were generated using the inverse-variance weighted method or Wald ratio method. Sensitivity analyses were undertaken to interrogate the robustness of the main findings. Two-step network MR and single-cell analysis were specifically designed to dissect pathway-level mediation and expression patterns of identified targets. <b>Results</b>: In the main analysis, genetically proxied calcium-channel blockers (odds ratio [OR]: 0.95, 95% confidence interval [CI]: 0.91-0.99, p=0.021) and vasodilator antihypertensives (OR: 0.86, 95% CI: 0.76-0.97, p=0.018) were suggestively associated with decreased risk of kidney cancer, whereas genetically proxied angiotensin-converting enzyme inhibitors (OR: 1.13, 95% CI: 1.00-1.27, p=0.043) was suggestively associated with increased risk of kidney cancer. Genetically proxied antiadrenergic agents (OR=0.94, 95% CI: 0.90-0.99, p=0.021) and centrally acting antihypertensives (OR=0.93, 95% CI: 0.88-0.98, p=0.010) were suggestively associated with a decreased risk of clear cell renal cell carcinoma. SMR analysis revealed that these suggestively significant associations might be driven by <i>CACNA1C</i>, <i>CALM1</i>, <i>ACE</i>, and <i>LTA4H</i>. Upon two-step network MR analyses, 10 pathways with directional consistency were identified, and the mediation proportion ranged from 3.22% to 7.12%. The influence of antihypertensive drugs on kidney cancer risk might be associated with their regulation of levels of blood cells and lipids. Single-cell analysis further revealed the expression patterns of the four identified targets in peripheral blood and tumor infiltrating immune cells. <b>Conclusion:</b> This study pioneers the integration of causal inference and single-cell omics to demonstrate that antihypertensive drugs modulate kidney cancer risk through target-specific mechanisms involving blood cell and lipid pathways. Our findings provide actionable targets (<i>CACNA1C</i>, <i>CALM1</i>, <i>ACE</i>, and <i>LTA4H</i>) for drug repurposing trials and underscore the clinical importance of personalized antihypertensive therapy in cancer prevention.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2690-2705"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325859","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":"Navigating the role of protein lactylation in prostate cancer and its implications for immunotherapy.","authors":"Dongzhang Li, Kaifeng Wang, Guantao Lou, Wangjian Li, Quan Ma, Yu'e Liu, Yongliang Chen","doi":"10.7150/jca.114137","DOIUrl":"10.7150/jca.114137","url":null,"abstract":"<p><p>Prostate cancer is an aggressive malignancy with high prevalence and significant mortality, characterized by its remarkable metabolic adaptability and immune complexity. Emerging evidence has highlighted the critical role of post-translational modifications (PTMs) in cancer biology, with protein lactylation gaining attention as a novel PTM with profound implications. Lactylation, derived from lactate, links the altered metabolic processes of tumor cells to diverse cellular functions, including epigenetic regulation and protein dynamics. It significantly influences tumor progression, immune evasion, and therapeutic resistance by modulating key immune cells within the tumor microenvironment. The immunosuppressive conditions created by lactate and lactylation favor tumor survival in prostate cancer. Thus, targeting lactylation offers innovative strategies for treating prostate cancer. By leveraging lactylation modulation, particularly in combination with immune checkpoint inhibitors, there is potential to enhance anti-tumor immune responses and improve treatment outcomes. This review explores the intersection of metabolic alterations and immune modulation, underscoring lactylation as a promising therapeutic avenue in prostate cancer.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2706-2719"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325865","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 Des-Gamma-Carboxy Prothrombin in AFP-Negative Hepatocellular Carcinoma Patients Following Liver Resection: <i>A Multicenter Study</i>.","authors":"Si-Yu Liu, Mu-Gen Dai, Wen-Feng Lu, Lei Liang, Jun-Wei Liu, Zhuo-Kai Li, Bin Ye","doi":"10.7150/jca.112394","DOIUrl":"10.7150/jca.112394","url":null,"abstract":"<p><p><b>Background:</b> Hepatocellular carcinoma (HCC) is a major global health concern with high postoperative recurrence rates. Des-gamma-carboxy prothrombin (DCP) is a promising biomarker for HCC prognosis, but its optimal cutoff value remains unclear, especially in AFP-negative patients. This study aimed to determine the ideal cutoff value of DCP in AFP-negative HCC patients following liver resection and to investigate its impact on long-term outcomes. <b>Methods:</b> This multicenter retrospective study included 661 patients who underwent curative HCC resection between 2015 and 2020 at three Chinese hospitals. Patients with AFP levels < 20 ng/mL were included. The primary endpoints were overall survival (OS) and time to recurrence (TTR). DCP levels were categorized as low (≤ 600 mAU/ml) and high (> 600 mAU/ml). <b>Results:</b> Among the 661 patients (median age 56 years; 88.4% men), 477 had low DCP levels and 184 had high DCP levels. Patients with high DCP levels had more aggressive tumor characteristics, including larger tumor size, microvascular invasion, and macrovascular invasion. The 5-year OS rates were 76.3% in the low DCP group vs. 57.6% in the high DCP group (<i>P</i> < 0.001), and the 5-year recurrence rates were 44.9% vs. 61.0% (<i>P</i> < 0.001), respectively. Multivariable analysis showed that high DCP levels were an independent risk factor for decreased OS (HR 1.548, 95%CI 1.135-2.111; <i>P</i> = 0.006) and increased TTR (HR 1.390, 95%CI 1.081-1.787; <i>P</i> = 0.010). <b>Conclusion:</b> A DCP cutoff value of 600 mAU/ml effectively stratifies AFP-negative HCC patients into high- and low-risk groups for survival and recurrence after liver resection. This cutoff value can guide clinical decision-making and improve prognostic accuracy.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2680-2689"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325870","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":"Revealing Potential Therapeutic Targets in Gastric Cancer through Inflammation and Protein-Protein Interaction Hub Networks.","authors":"Wei Wu, Guoliang Li, Lixin Chai, Yating Yin, Xin Xu, Chenlun Han, Hongyong Liu, Yi Cao, Yumiao Wang, Qunhao Guo, Wenxuan Chen, Peter Wang, Zhijian Pan","doi":"10.7150/jca.112218","DOIUrl":"10.7150/jca.112218","url":null,"abstract":"<p><p><b>Background:</b> Gastric cancer (GC) ranks second in incidence and mortality among digestive system cancer, following colorectal cancer. Currently treatment options are limited, and the prognosis for GC remains poor. <b>Methods:</b> Four bulk RNA sequencing (RNA-seq) datasets and two single-cell RNA sequencing (scRNA-seq) datasets were downloaded from the Gene Expression Omnibus (GEO) database. Initially, we identified differentially expressed genes (DEGs). The intersection list of inflammatory response-related DEGs (IRR-DEGs) was utilized for enrichment analyses. Hub genes were extracted from the protein-protein interaction (PPI) network of DEGs, exploring their expression in the context of scRNA-seq landscapes and cell-cell communication. IRR hub DEGs were identified, and pathway and receptor-ligand pairs were analyzed at this gene level. <b>Results:</b> The analysis identified 69 DEGs in GC. Among these, 8 IRR-DEGs (SPP1, TIMP1, SERPINF1, TNFAIP6, LGALS1, LY6E, MSR1, and SELE) were closely associated with 19 types of immune cells and various lymphocytes. Of the 12 hub genes (SPP1, TIMP1, FSTL1, THY1, COL4A1, FBN1, ASPN, COL10A1, COL5A1, THBS2, LUM, and SPARC), their expression is significantly enhanced in stem cells, primarily involving communication with monocytes, and four prognostic-related genes were discovered. Two IRR hub DEGs indicated that the SPP1 signaling pathway, specifically the SPP1-CD44 ligand-receptor pairs, plays a critical role. <b>Conclusion:</b> We have collectively identified 18 genes that could serve as biomarkers for future GC targeting. The discovery of the SPP1-CD44 ligand-receptor axis not only elucidates a novel inflammatory signaling pathway driving tumor progression, but also provides a potential therapeutic target for disrupting cancer-stromal interactions. Importantly, these biomarkers lay the foundation for developing precision immunotherapies that target the inflammatory-immune axis in GC management.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2720-2736"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325855","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":"Omega-6/Omega-3 Ratio as a Protective Factor in Lung Cancer: A Mendelian Randomization Study on Polyunsaturated Fatty Acids and Lung Adenocarcinoma Risk.","authors":"Cheng Wang, Ya Ding, Qikang Hu, Bin Wang, Shouzhi Xie, Zhi Yang, Zhe Zhang, Dexing Dai, An Xiong, Ruoman Sun, Yali Ling, Lei Qiu, Fenglei Yu, Zhongjian Xie, Muyun Peng","doi":"10.7150/jca.112416","DOIUrl":"10.7150/jca.112416","url":null,"abstract":"<p><p><b>Background:</b> While observational studies have reported conflicting associations between polyunsaturated fatty acids (PUFAs) and lung cancer risk, the causal role of specific PUFA subtypes remains unclear. <b>Methods:</b> Leveraging genome-wide association data from the UK Biobank and International Lung Cancer Consortium, we employed univariable, multivariable, and bidirectional Mendelian randomization (MR) analyses to investigate the causal effects of seven PUFA traits (including omega-3, DHA, EPA, omega-6, LA, AA, and the omega-6/omega-3 ratio) on lung cancer and its subtypes. <b>Results:</b> Our primary finding revealed a robust protective effect of a higher omega-6/omega-3 ratio against overall lung cancer (IVW: OR = 0.87; 95% CI: 0.78-0.96; <i>P_value</i> = 0.009) and lung adenocarcinoma (LUAD) (IVW: OR = 0.78; 95% CI: 0.67-0.89; <i>P_value</i> = 0.0005). Conversely, elevated omega-3 and DHA levels were associated with increased LUAD risk. These associations persisted after adjusting for BMI, smoking, and potential pleiotropy. <b>Conclusion:</b> This study provides the first causal evidence that a higher omega-6/omega-3 ratio reduces lung cancer risk, particularly LUAD, through multivariable and bidirectional Mendelian randomization analyses that account for BMI, smoking, and genetic pleiotropy. These findings highlight the ratio's potential as a novel and modifiable dietary target for prevention, offering actionable insights beyond prior studies focused on individual PUFA subtypes.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2649-2662"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325866","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}