Abstract
Simple SummaryThe establishment of molecular markers to predict response to neoadjuvant chemoradiotherapy (CRT) would help to avoid unnecessary toxicities and surgery delays in the clinical management of locally advanced rectal cancer (LARC) patients. Our aim here was to in-vestigate the clinical impact of miR-19b in this disease. Interestingly, our findings highlight the potential usefulness of miR-19b as a predictor of response to neoadjuvant CRT and outcome, and suggest PPP2R5E as a relevant miR-19b target in LARC.The standard treatment for patients with locally advanced colorectal cancer (LARC) is neoadjuvant 5-fluorouracil (5-FU) based chemoradiotherapy (CRT) followed by surgical mesorectal excision. However, the lack of response to this preoperative treatment strongly compromises patient outcomes and leads to surgical delays and undesired toxicities in those non-responder cases. Thus, the identification of effective and robust biomarkers to predict response to preoperative CRT represents an urgent need in the current clinical management of LARC. The oncomiR microRNA-19b (miR-19b) has been reported to functionally play oncogenic roles in colorectal cancer (CRC) cells as well as regulate 5-FU sensitivity and determine outcome in CRC patients. However, its clinical impact in LARC has not been previously investigated. Here, we show that miR-19b deregulation is a common event in this disease, and its decreased expression significantly associates with lower tumor size after CRT (p = 0.003), early pathological stage (p = 0.003), and absence of recurrence (p = 0.001) in LARC patients. Interestingly, low miR-19b expression shows a predictive value of better response to neoajuvant CRT (p < 0.001), and the subgroup of LARC patients with low miR-19b levels have a markedly longer overall (p = 0.003) and event-free survival (p = 0.023). Finally, multivariate analyses determined that miR-19b independently predicts both patient outcome and response to preoperative CRT, highlighting its potential clinical usefulness in the management of LARC patients.
Highlights
Colorectal carcinoma (CRC) is a highly prevalent multifactorial disease in the Western world, being the third leading cause of death from cancer
New therapeutic approaches are currently under study, the standard treatment recommended by European Society for Medical Oncology (ESMO) guidelines for locally advanced rectal cancer (LARC) is a preoperative chemoradiotherapy (CRT) based on 5fluorouracil or short-course preoperative radiotherapy (SCPRT) followed by a total mesorectal excision (TME) [3]
We evaluated the potential association of low miR-19b downregulation with molecular and clinical parameters in our LARC patient cohort
Summary
Colorectal carcinoma (CRC) is a highly prevalent multifactorial disease in the Western world, being the third leading cause of death from cancer. In Spain, more than 44,000 new colorectal cases are diagnosed each year and, around 15,000 deaths are reported annually [1]. Rectal carcinoma represents almost 30% of all diagnosed colorectal cancers. New therapeutic approaches are currently under study, the standard treatment recommended by European Society for Medical Oncology (ESMO) guidelines for locally advanced rectal cancer (LARC) is a preoperative chemoradiotherapy (CRT) based on 5fluorouracil (intravenous or oral formulation, capecitabine) or short-course preoperative radiotherapy (SCPRT) followed by a total mesorectal excision (TME) [3]. Several studies have demonstrated that this therapeutic strategy leads to a better local response and a lower local relapse rate compared to TME alone or followed by adjuvant CRT [4,5]
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