The association of hypoxia-inducible factor-1 alpha expression, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio with three-year progression-free survival in locally advanced colorectal cancer patients.

Introduction: Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide and ranks among the top three in Indonesia. Most patients were diagnosed in a locally advanced stage, with a high recurrence rate despite standard oxaliplatin-based chemotherapy. The hypoxic tumor microenvironment through activation of HIF-1α and systemic inflammation reflected by the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) could be associated with the tumor progression. Aim: To evaluate the association of HIF-1α expression, NLR, and PLR with three-year progression-free survival (PFS) in locally advanced CRC patients. Methods: This retrospective cohort study included 50 patients with high-risk stage II and stage III CRC who underwent surgical resection and adjuvant oxaliplatin-based chemotherapy in Cipto Mangunkusumo National Hospital. HIF-1α expression was assessed by immunohistochemistry, while NLR and PLR were calculated from pre-treatment blood tests. Data were analyzed using Kaplan–Meier and Cox regression methods, with p<0.05 considered statistically significant. Results: The median HIF-1α expression was 96.32%, with a cut-off value of 96.51% (AUC 0.472; p=0.746). There was no significant association between HIF-1α expression and three-year PFS (HR 1.274; p=0.495). The cut-off points for NLR and PLR were 3.46 (AUC 0.486; p=0.872) and 198.31 (AUC 0.505; p=0.952), respectively, and both were not significantly associated with three-year PFS (NLR: HR 0.947; p=0.874; PLR: HR 1.060; p=0.869). Conclusions: HIF-1α expression, NLR, and PLR were not significantly associated with three-year progression-free survival in locally advanced CRC patients.