胶原相关基因与前列腺癌相关性的综合分析。
Integrative analysis regarding the correlation between collagen-related genes and prostate cancer.
发表日期:2024 Aug 22
作者:
Yunfei Xiao, Cong Lai, Jintao Hu, Yelisudan Mulati, Xiaoting Xu, Jiawen Luo, Degeng Kong, Cheng Liu, Kewei Xu
来源:
Epigenetics & Chromatin
摘要:
前列腺癌(PCa)是男性常见的恶性肿瘤,由于复发和转移而导致死亡率不断上升。最近的研究阐明了胶原蛋白在肿瘤微环境中的关键调节作用,显着影响肿瘤进展。因此,本研究致力于检查与胶原蛋白相关的基因与 PCa 预后之间的关系,目的是揭示它们之间任何可能的关联。前列腺癌个体的基因表达数据来自 TCGA 存储库。鉴定出胶原蛋白相关基因,从而开发出与生化无复发生存(BRFS)相关的风险评分模型。制作了将风险评分与基本临床因素相结合的预后列线图,并评估了疗效。通过各种检测,包括 CCK8、侵袭、迁移、细胞克隆和伤口愈合,证实了关键胶原蛋白相关基因对细胞行为的影响。使用免疫组织化学检测来评估前列腺癌组织样本中的 PLOD3 表达。我们的研究确定了四个关键的胶原相关基因(PLOD3、COL1A1、MMP11、FMOD)具有显着意义。生存分析显示,根据风险评分模型,低风险群体的预后显着改善。风险评分与前列腺癌预后密切相关。研究人员随后创建了列线图,证明了强大的预测功效和实质性的临床适用性。值得注意的是,PLOD3 表达的抑制显着阻碍了 PCa 细胞的增殖、侵袭、迁移和集落形成能力。风险评分源自四种胶原相关蛋白基因,有可能作为患者 BRFS 的精确预后指标。同时,我们的研究已经确定了与胶原蛋白相关的潜在治疗靶点。值得注意的是,PLOD3 在临床标本的癌症和癌旁组织中存在差异表达,并且还通过体外研究进行了验证,并显示其沉默后可抑制 PCa 肿瘤发生。© 2024。作者。
Prostate cancer (PCa) is a common malignancy in men, with an escalating mortality rate attributed to Recurrence and metastasis. Recent studies have illuminated collagen's critical regulatory role within the tumor microenvironment, significantly influencing tumor progression. Accordingly, this investigation is dedicated to examining the relationship between genes linked to collagen and the prognosis of PCa, with the objective of uncovering any possible associations between them.Gene expression data for individuals with prostate cancer were obtained from the TCGA repository. Collagen-related genes were identified, leading to the development of a risk score model associated with biochemical recurrence-free survival (BRFS). A prognostic nomogram integrating the risk score with essential clinical factors was crafted and evaluated for efficacy. The influence of key collagen-related genes on cellular behavior was confirmed through various assays, including CCK8, invasion, migration, cell cloning, and wound healing. Immunohistochemical detection was used to evaluate PLOD3 expression in prostate cancer tissue samples.Our study identified four key collagen-associated genes (PLOD3, COL1A1, MMP11, FMOD) as significant. Survival analysis revealed that low-risk groups, based on the risk scoring model, had significantly improved prognoses. The risk score was strongly associated with prostate cancer prognosis. Researchers then created a nomogram, which demonstrated robust predictive efficacy and substantial clinical applicability.Remarkably, the suppression of PLOD3 expression notably impeded the proliferation, invasion, migration, and colony formation capabilities of PCa cells.The risk score, derived from four collagen-associated genes, could potentially act as a precise prognostic indicator for BRFS of patients. Simultaneously, our research has identified potential therapeutic targets related to collagen. Notably, PLOD3 was differentially expressed in cancer and para-cancer tissues in clinical specimens and it also was validated through in vitro studies and shown to suppress PCa tumorigenesis following its silencing.© 2024. The Author(s).