Identification of proteins associated with treatment response of neoadjuvant chemoradiotherapy in rectal mucinous adenocarcinoma by co-expression network analysis based on proteomic analysis

Abstract

For rectal mucinous adenocarcinoma (MAC), identifying biomarkers of neoadjuvant chemoradiotherapy (NCRT) response has become imperative. This study applied label-free mass spectrometry and weighted gene co-expression network analysis to identify hub proteins in association with the NCRT response in 20 rectal MAC patients. We identified 131 differentially abundant proteins and 7 candidate proteins associated with the NCRT response. The immunostaining expressions of six proteins (ENOA, ILEU, MDHM, RM11, PTGDS, and RL3) were significantly associated with the NCRT response. Logistic regression analysis revealed that ENOA (OR = 6.275, P = 0.006) was independent risk hub protein for the NCRT response. Tow hub proteins (ENOA and PTGDS) were identified as significant risk factors by Cox regression analysis. A prognostic risk score system was constructed: risk score = (0.910 × EXPENOA) + (−1.519 × EXPPTGDS), and found to be an independent predictor of DFS in rectal MAC patients (HR = 10.308, P < 0.001). Our study suggested that ENOA may be a novel biomarker for the NCRT response and prognosis in rectal MAC patients. A two-hub-protein-based risk score system might be used for predicting tumor recurrence in rectal MAC patients. SignificanceNCRT resistance is a major problem in the treatment of rectal MAC patients. Identifying robust predictive biomarkers for NCRT resistance is beneficial to the stratified treatment of rectal MAC patients. In this study, label-free mass spectrometry and weighted gene co-expression network analysis identified ENOA as a potential novel biomarker for the NCRT response and prognosis. ENOA may be involved in the process of the NCRT resistance and tumor recurrence through the carbon metabolism pathway.