Survival Impacts of Mitochondrial Status in Esophageal Squamous Cell Carcinoma Patients

Abstract

Background Little is known about the survival impacts of mitochondrial status in esophageal squamous cell carcinoma (ESCC) patients who undergo neoadjuvant chemotherapy (NAC) followed by surgery. Methods In total, 260 pre-NAC samples from ESCC patients were analyzed. Mitochondrial status was estimated employing an objective, immunohistochemistry-based system (Mito-score). Mito-scores were dichotomized according to the median value of our cohort. We also evaluated the immune microenvironment (CD4, CD8, Foxp3, HLA class-1, Ki-67 and programmed death ligand-1) on pre-NAC specimens. Multivariate Cox hazards models were applied to determine independent predictors of poor overall survival (OS). Results Patients with cT3–4 tumors had higher Mito-scores than those with cT1–2 tumors (p = 0.06), and good responders to NAC had significantly higher Mito-scores than poor responders to NAC (p = 0.04). CD8 cells and Ki-67 expression were significantly higher in Mito-high than Mito-low tumors (p = 0.017 and p < 0.001, respectively). Patients with low Mito-scores had significantly poorer OS than those with high Mito-scores (3-year OS: 57.6% vs. 68.2%; p = 0.03). A survival difference by Mito-score was evident in cStage III–IV patients (3-year OS: low 50.6% vs. high 66.1%; p = 0.006). Multivariable analysis revealed that a low Mito-score (hazard ratio 1.59, 95% confidence interval 1.12–2.24; p = 0.009) as well as pT3–4 disease (p < 0.001) and pN2–3 disease (p < 0.001) were independently associated with poor OS outcomes. Conclusions A low Mito-score before NAC had a significant survival impact in ESCC patients, especially in those with advanced disease. Mitochondrial status might be associated with tumor aggressiveness and responsiveness to NAC, thereby possibly affecting the survival outcomes of ESCC patients.