Background: This study aimed to investigate the molecular profiles of 237 stage III CRC patients from the international IDEA study. It also sought to correlate these profiles with Toll-like and vitamin D receptor polymorphisms, clinicopathological and epidemiological characteristics, and patient outcomes. Methods: Whole Exome Sequencing and PCR-RFLP on surgical specimens and blood samples, respectively, were performed to identify molecular profiling and the presence of Toll-like and vitamin D polymorphisms. Bioinformatic analysis revealed mutational status. Results: Among the enrolled patients, 63.7% were male, 66.7% had left-sided tumors, and 55.7% received CAPOX as adjuvant chemotherapy. Whole exome sequencing identified 59 mutated genes in 11 different signaling pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) CRC panel. On average, patients had 8 mutated genes (range, 2–21 genes). Mutations inARAFandMAPK10emerged as independent prognostic factors for reduced DFS (p= 0.027 andp< 0.001, respectively), while RAC3 andRHOAgenes emerged as independent prognostic factors for reduced OS (p= 0.029 andp= 0.006, respectively). Right-sided tumors were also identified as independent prognostic factors for reduced DFS (p= 0.019) and OS (p= 0.043). Additionally, patients with tumors in the transverse colon had mutations in genes related to apoptosis,PIK3-Akt,Wnt, andMAPKsignaling pathways. Conclusions: Molecular characterization of tumor cells can enhance our understanding of the disease course. Mutations may serve as promising prognostic biomarkers, offering improved treatment options. Confirming these findings will require larger patient cohorts and international collaborations to establish correlations between molecular profiling, clinicopathological and epidemiological characteristics and clinical outcomes.
背景：本研究旨在分析国际IDEA研究中237例III期结直肠癌（CRC）患者的分子特征，并探讨其与Toll样受体及维生素D受体基因多态性、临床病理特征、流行病学特征及患者预后的相关性。方法：分别对手术标本进行全外显子组测序，对血液样本进行PCR-RFLP分析，以确定分子特征及Toll样受体和维生素D受体基因多态性。通过生物信息学分析揭示基因突变状态。结果：入组患者中63.7%为男性，66.7%为左侧肿瘤，55.7%接受CAPOX方案辅助化疗。全外显子组测序在京都基因与基因组百科全书（KEGG）结直肠癌基因集中识别出涉及11条信号通路的59个突变基因。患者平均携带8个突变基因（范围2-21个）。ARAF与MAPK10基因突变是无病生存期（DFS）缩短的独立预后因素（p值分别为0.027和<0.001），而RAC3与RHOA基因突变是总生存期（OS）缩短的独立预后因素（p值分别为0.029和0.006）。右侧肿瘤也被确定为DFS（p=0.019）和OS（p=0.043）缩短的独立预后因素。此外，横结肠肿瘤患者携带与细胞凋亡、PIK3-Akt、Wnt及MAPK信号通路相关的基因突变。结论：肿瘤细胞的分子特征分析可深化对疾病进程的理解。基因突变可能成为有前景的预后生物标志物，为优化治疗方案提供依据。验证这些发现需要更大规模的患者队列和国际合作，以明确分子特征、临床病理及流行病学特征与临床结局之间的关联。
肿瘤(癌症)患者之家