Evaluation of PINK1 protein expression as a predictive marker for the efficacy of adjuvant chemotherapy in colorectal cancer: a retrospective study.

BACKGROUND

PTEN-induced kinase 1 (PINK1) is involved in mitochondrial quality control via mitophagy, and recent studies have reported that its overexpression is associated with chemoresistance and poor prognosis in multiple malignant tumors. However, the clinical significance of PINK1 expression in colorectal cancer remains unclear. In this study, we investigated the association among PINK1 protein expression, clinicopathological factors, and prognosis in patients with colorectal cancer who underwent adjuvant chemotherapy after curative surgery.

METHODS

We retrospectively analyzed 83 patients with colorectal cancer who underwent curative surgery and fluoropyrimidine-based adjuvant chemotherapy in 2016. Expression of PINK1 and autophagy-related protein LC3 was evaluated by immunohistochemical staining, and the percentage of positive cells and staining intensity were scored. The association between PINK1 expression and the prognosis of 25 patients with confirmed recurrence was analyzed in detail. Survival analysis was performed using the Kaplan-Meier method and Cox proportional hazards models. Furthermore, in 11 cases with RNA sequencing analysis available among the recurrent cases, gene expression profiles were compared based on PINK1 expression levels, and biological characteristics were evaluated.

RESULTS

PINK1 high expression was observed in 42.2% of the cases. No significant association was found between PINK1 and LC3 expression and overall survival (OS) or recurrence-free survival (RFS). However, in the recurrence group (n = 25), PINK1 high expression was significantly associated with a shorter OS (p = 0.024). In multivariate analysis, histological differentiation grade and high PINK1 expression were identified as independent prognostic factors (PINK1: hazard ratio 5.345, 95% confidence interval, 1.343-21.276; p = 0.017). RNA sequencing revealed increased expression of genes associated with autophagy and amino acid transport in the high PINK1 expression group.

CONCLUSIONS

High PINK1 expression is associated with poor prognosis in colorectal cancer recurrence and may be involved in the promotion of chemotherapy resistance and cellular stress tolerance. PINK1 is a promising biomarker as a prognostic predictor and a new therapeutic target for adjuvant chemotherapy after surgery.