Network Mapping of Molecular Biomarkers Influencing Radiation Response in Rectal Cancer

Abstract

Preoperative radiotherapy (RT) plays an important role in the management of locally advanced rectal cancer (RC). Tumor regression after RT shows marked variability, and robust molecular methods are needed to help predict likely response. The aim of this study was to review the current published literature and use Gene Ontology (GO) analysis to define key molecular biomarkers governing radiation response in RC. A systematic review of electronic bibliographic databases (Medline, Embase) was performed for original articles published between 2000 and 2015. Biomarkers were then classified according to biological function and incorporated into a hierarchical GO tree. Both significant and nonsignificant results were included in the analysis. Significance was binarized on the basis of univariate and multivariate statistics. Significance scores were calculated for each biological domain (or node), and a direct acyclic graph was generated for intuitive mapping of biological pathways and markers involved in RC radiation response. Seventytwo individual biomarkers across 74 studies were identified. On highest-order classification, molecular biomarkers falling within the domains of response to stress, cellular metabolism, and pathways inhibiting apoptosis were found to be the most influential in predicting radiosensitivity. Homogenizing biomarker data from original articles using controlled GO terminology demonstrated that cellular mechanisms of response to RT in RC-in particular the metabolic response to RT-may hold promise in developing radiotherapeutic biomarkers to help predict, and in the future modulate, radiation response.

Clinical Effect of Radiotherapy Combined with Capecitabine after Neoadjuvant Therapy for Rectal Cancer

“…Due to the higher concentration of TP in tumor cells and the lower concentration of TP in normal cells, the activity of TP in tumor cells can be enhanced by radiotherapy, and the effect of 5-FU can be further improved. Therefore, radiotherapy combined with capecitabine in rectal cancer patients after neoadjuvant therapy has great advantages [ 19 , 20 ]. In recent years, many scholars have proposed that radiotherapy combined with capecitabine in rectal cancer patients after neoadjuvant therapy can reduce patients' adverse reactions and has a positive effect on improving patients' survival rate [ 21 , 22 ].…”

Genomic-driven nutritional interventions for radiotherapy-resistant rectal cancer patient

“…RT response is governed by various molecular mechanisms including response to stress, cell death, and cell metabolism 6 . Current strategies to improve radioresponse focus on the modulation of cell death and response to stress using chemotherapies, such as fluorouracil (5-FU), capecitabine, gemcitabine, and cisplatin, to enhance tumor sensitivity to RT 7 .…”

Pan-Cancer Analysis of Radiotherapy Benefits and Immune Infiltration in Multiple Human Cancers

“…Further, Speers et al created a human breast cancer (BRCA)-specific radiosensitivity signature (RSS) with biological relevance and validated this signature for the prediction of local recurrence [8]. Finally, Gene Ontology (GO) analyses were employed to define key molecular biomarkers governing response to radiation in rectal cancer [9]. However, all these studies were based on the intrinsic radiation response of tumor cells and the effects of the TME on this response were ignored [10,11].…”