目的:前列腺癌(PCa)是男性常见的恶性肿瘤,死亡率上升归因于复发和转移。最近的研究已经阐明了胶原蛋白在肿瘤微环境中的关键调节作用。显著影响肿瘤进展。因此,这项研究致力于研究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。
方法:前列腺癌患者的基因表达数据来自TCGA库。确定了与胶原相关的基因,导致与生化无复发生存期(BRFS)相关的风险评分模型的发展。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。通过各种试验证实了关键胶原相关基因对细胞行为的影响。包括CCK8,入侵,迁移,细胞克隆,伤口愈合。免疫组织化学检测用于评估前列腺癌组织样品中的PLOD3表达。
结果:我们的研究确定了四个关键的胶原相关基因(PLOD3、COL1A1、MMP11、FMOD)具有显著性。生存分析显示,低风险人群,基于风险评分模型,有显著改善预后。风险评分与前列腺癌预后密切相关。然后研究人员创建了一个列线图,这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表达的抑制明显阻碍了增殖,入侵,迁移,和PCa细胞的集落形成能力。
结论:风险评分,来自四个胶原蛋白相关基因,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在临床标本中的癌症和癌旁组织中差异表达,并且还通过体外研究进行了验证,并显示出在沉默后抑制PCa肿瘤发生。
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.