Prognostic Value of LC3A Protein Expression Patterns in Rectal Cancer Tumors

Background/Objectives: Autophagy is a conserved self-degradation process by which cells break down and recycle their cellular constituents. This process is activated by various stressors, including nutrient deprivation and DNA damage, and has also been associated with tumor progression. In the present study, we aimed to determine the expression patterns, clinicopathological significance, and prognostic value of the autophagy marker microtubule-associated protein 1 light chain 3 alpha (LC3A)-an essential component of autophagic vacuoles-in rectal cancer. Methods: LC3A reactivity was measured by immunohistochemistry in tumor samples from 243 patients who underwent surgery for rectal cancer. Results: Three distinct patterns of LC3A expression were identified: diffuse cytoplasmic, perinuclear, and stone-like structures (SLS). In Kaplan-Meier survival analyses, patients positive for the SLS pattern of LC3A staining in the tumor periphery (TP) had worse overall survival (OS; p = 0.001) and disease-free survival (DFS; p = 0.030) than those without SLSs in this region, as determined by the log-rank test. When patients were stratified by tumor stage, this result was significant in those with stage T3-T4 (OS, p < 0.001; DFS, p = 0.001) but not T1-T2 disease. Multivariate Cox regression analysis further showed an association between TP-localized LC3A SLS positivity and reduced OS for the overall cohort (hazard ratio [HR] = 2.6313, 95% confidence interval [CI]: 1.090-6.349, p = 0.031) and specifically those in the T3-T4 subgroup (HR = 3.347, 95% CI: 1.657-6.760, p = 0.001). Conclusions: Our findings suggest that positivity for SLSs in the TP may hold clinical value as a biomarker for survival prognosis in rectal cancer patients.