Objectives: Clear cell renal cell carcinoma (ccRCC) may later metastasize despite curative surgery. This study asked whether transcriptomic alterations detectable at nephrectomy are associated with subsequent metastatic progression, and whether such signals retain prognostic relevance in overt metastatic disease. Methods: Bulk RNA sequencing was performed in 30 ccRCC patients without metastasis at surgery; 4 developed distant metastasis during follow-up. Differential expression, enrichment, and network analyses identified hub genes, which were screened by ROC analysis with bootstrap optimism correction. External validation used TCGA-KIRC focusing on patients metastatic at baseline (M1) to evaluate overall and disease-specific survival with multivariable Cox models (per-SD expression, adjusted for age, sex, and stage); Kaplan–Meier curves were shown for visualization only. Results: Fifty-nine DEGs distinguished patients who later metastasized from those who remained metastasis-free, with enrichment in mitotic and chromosomal-segregation pathways. Five hub genes (BASP1,CDCA8,KIF2C,LMNB1,TROAP) showed high discrimination in the discovery set (optimism-corrected AUC ~0.92–0.93). In TCGA-M1,CDCA8, andTROAPwere consistently associated with worse survival and remained significant in multivariable models. Conclusions: Dysregulation of mitotic control may underlie latent metastatic competence in ccRCC.CDCA8andTROAPemerge as candidate prognostic biomarkers, linking postoperative metastatic progression in an initially M0 cohort with survival in metastatic disease. These hypothesis-generating findings warrant validation in larger, prospective cohorts.
目的：透明细胞肾细胞癌（ccRCC）在根治性手术后仍可能发生转移。本研究旨在探讨肾切除术时可检测到的转录组学改变是否与后续转移进展相关，以及此类信号在显性转移疾病中是否仍具有预后意义。方法：对30例手术时无转移的ccRCC患者进行批量RNA测序；其中4例在随访期间出现远处转移。通过差异表达、富集和网络分析确定枢纽基因，并采用ROC分析结合Bootstrap乐观校正进行筛选。外部验证使用TCGA-KIRC数据库，重点关注基线时已发生转移（M1）的患者，通过多变量Cox模型（按每标准差表达量，校正年龄、性别和分期）评估总生存期和疾病特异性生存期；Kaplan–Meier曲线仅用于可视化展示。结果：59个差异表达基因可区分后续发生转移与未转移的患者，这些基因富集于有丝分裂和染色体分离通路。五个枢纽基因（BASP1、CDCA8、KIF2C、LMNB1、TROAP）在发现集中显示出高区分度（乐观校正AUC约0.92–0.93）。在TCGA-M1数据中，CDCA8和TROAP与较差的生存率持续相关，且在多变量模型中仍保持显著性。结论：有丝分裂调控失调可能是ccRCC潜在转移能力的基础。CDCA8和TROAP作为候选预后生物标志物，将初始M0队列的术后转移进展与转移性疾病生存期联系起来。这些假设性发现需要在更大规模的前瞻性队列中进行验证。
肿瘤(癌症)患者之家