Impact of mutation profiles identified by next generation sequencing on clinicopathological features and survival in metastatic colorectal cancers

Colorectal cancer is a disease with increasing incidence and is a major cause of morbidity and mortality worldwide. It ranks as the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths. Due to its high mortality rate, research on colorectal cancer has significantly increased in recent years. When the pathogenesis of colorectal cancer is not fully understood, conventional treatment approaches may fall short. As a result, studies focusing on the genetic structure of tumors have gained importance. Particularly, next-generation sequencing technologies have enabled detailed profiling of tumor genetics, paving the way for targeted therapeutic strategies. In this study, we retrospectively analyzed patients diagnosed with colorectal cancer (CRC) between 2012 and 2024 at the Medical Oncology Outpatient Clinic of Trakya University Faculty of Medicine Hospital and/or diagnosed elsewhere but followed at the same hospital, all of whom underwent genetic mutation analysis using next-generation sequencing. The study excluded patients who were diagnosed at our institution but received follow-up care elsewhere, those without next-generation sequencing analysis, and those who declined chemotherapy treatment. The study included 307 patients whose demographic data, presenting symptoms at diagnosis, tumor localization, stage, metastatic sites, tumor markers, treatment modalities, and survival outcomes were evaluated. When analyzing mutations identified by next-generation sequencing in relation to gender and age at diagnosis, the presence of APC and FBXW7 mutations was found to be significantly higher in male patients compared to females. No other statistically significant differences were observed in terms of gender or age across other mutations. Examination of the relationship between tumor localization and mutations revealed no statistically significant associations based on chisquare analysis. Likewise, no significant differences were found between genetic mutations and the presence of liver or lung metastases. Notably, perineural invasion had a statistically significant negative impact on survival. Among the mutations evaluated by Kaplan-Meier survival analysis, TP53, the RAS gene family, and EGFR mutations showed statistically significant effects on survival. Although patients with FBXW7 mutations exhibited shorter overall survival, this difference was not statistically significant. Given the retrospective nature of this study and the limited size and heterogeneity of the patient cohort, further large-scale, prospective, and randomized studies are needed to clarify the clinical implications of these findings.