Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou, Guangdong, 510000, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510000, China.
BMC Cancer. 2024 Aug 22;24(1):1038. doi: 10.1186/s12885-024-12783-9.
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.
前列腺癌（PCa）是男性常见的恶性肿瘤，其死亡率的上升归因于复发和转移。最近的研究表明，胶原蛋白在肿瘤微环境中具有关键的调节作用，对肿瘤的进展有重要影响。因此，本研究致力于探讨与胶原蛋白相关的基因与 PCa 预后之间的关系，旨在揭示它们之间可能存在的关联。
从 TCGA 数据库中获取前列腺癌患者的基因表达数据。确定与胶原蛋白相关的基因，构建与生化无复发生存（BRFS）相关的风险评分模型。构建并评估了一个整合风险评分和重要临床因素的预后列线图，以评估其疗效。通过 CCK8、侵袭、迁移、细胞克隆和划痕愈合等实验，证实了关键胶原蛋白相关基因对细胞行为的影响。免疫组织化学检测用于评估前列腺癌组织样本中 PLOD3 的表达。
本研究确定了四个关键的胶原蛋白相关基因（PLOD3、COL1A1、MMP11、FMOD）作为重要的标志物。生存分析显示，基于风险评分模型，低风险组的预后明显改善。风险评分与前列腺癌的预后密切相关。研究人员随后构建了一个列线图，该列线图具有较强的预测效能和广泛的临床应用价值。值得注意的是，抑制 PLOD3 的表达显著抑制了 PCa 细胞的增殖、侵袭、迁移和集落形成能力。
由四个与胶原蛋白相关的基因组成的风险评分模型可能成为预测 BRFS 的精确预后指标。同时，我们的研究还确定了与胶原蛋白相关的潜在治疗靶点。值得注意的是，在临床标本中，PLOD3 在癌组织和癌旁组织中均有差异表达，并且通过体外研究进行了验证，证实其沉默后可抑制 PCa 的肿瘤发生。
