METHODS: Levels of MtDNA-CN were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) in a cohort of 308 CRC patients with dMMR comprising 180 stage II and 128 stage III patients. Clinicopathologic and therapeutic data were collected. The study examined the association between mtDNA-CN levels and prognosis, as well as the impact of ACT benefit on dMMR CRC patients. Subgroup analyses were performed based mainly on tumor stage and mtDNA-CN level. Kaplan-Meier and Cox regression models were used to evaluate the effect of mtDNA-CN on disease-free survival (DFS) and overall survival (OS).
RESULTS: A substantial reduction in mtDNA-CN expression was observed in tumor tissue, and higher mtDNA-CN levels were correlated with improved DFS (73.4% vs 85.7%; P = 0.0055) and OS (82.5% vs 90.3%; P = 0.0366) in dMMR CRC patients. Cox regression analysis identified high mtDNA-CN as an independent protective factor for DFS (hazard ratio [HR] 0.547; 95% confidence interval [CI] 0.321-0.934; P = 0.0270) and OS (HR 0.520; 95% CI 0.272-0.998; P = 0.0492). Notably, for dMMR CRC patients with elevated mtDNA-CN, ACT significantly improved DFS (74.6% vs 93.4%; P = 0.0015) and OS (81.0% vs 96.7%; P = 0.0017), including those with stage II or III disease.
CONCLUSIONS: The mtDNA-CN levels exhibited a correlation with the prognosis of stage II or III CRC patients with dMMR. Elevated mtDNA-CN emerges as a robust prognostic factor, indicating improved ACT outcomes for stages II and III CRC patients with dMMR. These findings suggest the potential utility of mtDNA-CN as a biomarker for guiding personalized ACT treatment in this population.
方法:使用定量实时聚合酶链反应(qRT-PCR)评估308例dMMRCRC患者的MtDNA-CN水平,包括180例II期和128例III期患者。收集临床病理和治疗数据。该研究检查了mtDNA-CN水平与预后之间的关系,以及ACT获益对dMMRCRC患者的影响。亚组分析主要基于肿瘤分期和mtDNA-CN水平进行。采用Kaplan-Meier和Cox回归模型评价mtDNA-CN对无病生存期(DFS)和总生存期(OS)的影响。
结果:在肿瘤组织中观察到mtDNA-CN表达显著减少,在dMMRCRC患者中,较高的mtDNA-CN水平与改善的DFS(73.4%vs85.7%;P=0.0055)和OS(82.5%vs90.3%;P=0.0366)相关。Cox回归分析确定高mtDNA-CN是DFS(风险比[HR]0.547;95%置信区间[CI]0.321-0.934;P=0.0270)和OS(HR0.520;95%CI0.272-0.998;P=0.0492)的独立保护因素。值得注意的是,对于mtDNA-CN升高的dMMRCRC患者,ACT显著提高了DFS(74.6%vs93.4%;P=0.0015)和OS(81.0%vs96.7%;P=0.0017),包括患有II期或III期疾病的患者。
结论:mtDNA-CN水平与患有dMMR的II期或III期CRC患者的预后相关。mtDNA-CN升高是一个强有力的预后因素,提示有dMMR的II期和III期CRC患者的ACT结局改善。这些发现表明mtDNA-CN作为指导该人群中个性化ACT治疗的生物标志物的潜在用途。