Lincp21-RNA as Predictive Response Marker for Preoperative Chemoradiotherapy in Rectal Cancer.

Jose Carlos Benitez,Mariano Monzo,Melissa Acosta-Plasencia,Tania Díaz,Luis Cirera,Alfons Navarro,Carme Ferrer,Benjamin Besse,Marc Campayo

doi:10.3390/jpm11050420

Abstract

Preoperative chemoradiotherapy (CRT) is a standard treatment for locally advanced rectal cancer (RC) patients, but its use in non-responders can be associated with increased toxicities and resection delay. LincRNA-p21 is a long non-coding RNA involved in the p53 pathway and angiogenesis regulation. We aimed to study whether lincRNA-p21 expression levels can act as a predictive biomarker for neoadjuvant CRT response. We analyzed RNAs from pretreatment biopsies from 70 RC patients treated with preoperative CRT. Pathological response was classified according to the tumor regression grade (TRG) Dworak classification. LincRNA-p21 expression was determined by RTqPCR. The results showed that lincRNA-p21 was upregulated in stage III tumors (p = 0.007) and in tumors with the worst response regarding TRG (p = 0.027) and downstaging (p = 0.016). ROC curve analysis showed that lincRNA-p21 expression had the capacity to distinguish a complete response from others (AUC:0.696; p = 0.014). LincRNA-p21 was shown as an independent marker of preoperative CRT response (p = 0.047) and for time to relapse (TTR) (p = 0.048). In conclusion, lincRNA-p21 is a marker of advanced disease, worse response to neoadjuvant CRT, and shorter TTR in locally advanced RC patients. The study of lincRNA-p21 may be of value in the individualization of pre-operative CRT in RC.

Highlights

Rectal cancer (RC) accounts for approximately one-third of all colorectal tumors (CRC) and remains the third most common cancer worldwide and the second leading cause of cancer-related death in the world [1]
We aimed to evaluate whether lincRNA-p21 can act as a predictive biomarker for CRT response in a 70-patient cohort of RC treated before resection
Sixty-one (87.1%) patients reported stage III and 9 (12.9%) stage II; 52 (74.3%) patients were assessed for tumor regression grade (TRG) 0–3, and 18 (25.7%) reported pathological complete response (TRG 4, ypT0N0); 64.3% of downstaging was shown

Summary

Introduction

Rectal cancer (RC) accounts for approximately one-third of all colorectal tumors (CRC) and remains the third most common cancer worldwide and the second leading cause of cancer-related death in the world [1]. Despite the adoption of adjuvant postoperative chemotherapy, patients are more than twice as likely to present with a distant recurrence rather than tumor regrowth at the primary site [5,6]. This situation emphasizes the urgency of devising upfront treatment strategies aimed at controlling obscure micro-metastases. Biomarkers to identify patients at high risk of relapse or lack of response are needed to guide treatment options and improve survival rates [11], and non-coding RNAs are promising candidates [12,13]

Objectives

Methods

Results

Discussion

Conclusion