TY - JOUR
T1 - Potential of miR-21 to Predict Incomplete Response to Chemoradiotherapy in Rectal Adenocarcinoma
AU - Ourô, Susana
AU - Mourato, Cláudia
AU - Velho, Sónia
AU - Cardador, André
AU - Ferreira, Marisa P.
AU - Albergaria, Diogo
AU - Castro, Rui E.
AU - Maio, Rui
AU - Rodrigues, Cecília M.P.
N1 - Funding: This work has received funding from European Structural and Investment Funds through the COMPETE Programme Grant LISBOA-01-0145-FEDER-016405, from National Funds through Fundação para a Ciência e Tecnologia Programme grant SAICTPAC/0019/2015 and by a cholar from the Portuguese Society of Coloproctology as Investigation in Coloproctology Research Prize 2016–2018.
PY - 2020/10/27
Y1 - 2020/10/27
N2 - Background: Patients with locally advanced rectal adenocarcinoma (LARC) are treated with neoadjuvant chemoradiotherapy (CRT). However, biomarkers for patient selection are lacking, and the association between miRNA expression and treatment response and oncological outcomes is unclear. Objectives: To investigate miRNAs as predictors of response to neoadjuvant CRT and its association with oncological outcomes. Methods: This retrospective study analyzed miRNA expression (miR-16, miR-21, miR-135b, miR-145, and miR-335) in pre- and post-chemoradiation rectal adenocarcinoma tissue and non-neoplastic mucosa in 91 patients treated with neoadjuvant CRT (50.4 Gy) and proctectomy. Two groups were defined: a pathological complete responders group (tumor regression grade—TRG 0) and a pathological incomplete responders group (TRG 1, 2, and 3). Results: miR-21 and miR-135b were upregulated in tumor tissue of incomplete responders comparing with non-neoplastic tissue (p = 0.008 and p < 0.0001, respectively). Multivariate analysis showed significant association between miR-21 in pre-CRT tumor tissue and response, with a 3.67 odds ratio (OR) of incomplete response in patients with higher miR-21 levels (p = 0.04). Although with no significance, patients treated with 5-fluorouracil (5-FU) presented reduced odds of incomplete response compared with those treated with capecitabine (OR = 0.19; 95% confidence interval (CI) 0.03–1.12, p = 0.05). Moreover, significant differences were seen in overall survival (OS) in relation to clinical TNM stage (p = 0.0004), cT (p = 0.0001), presence of distant disease (p = 0.002), mesorectal tumor deposits (p = 0.003), and tumor regression grade (p = 0.04). Conclusion: miR-21 may predict response to CRT in rectal cancer (RC).
AB - Background: Patients with locally advanced rectal adenocarcinoma (LARC) are treated with neoadjuvant chemoradiotherapy (CRT). However, biomarkers for patient selection are lacking, and the association between miRNA expression and treatment response and oncological outcomes is unclear. Objectives: To investigate miRNAs as predictors of response to neoadjuvant CRT and its association with oncological outcomes. Methods: This retrospective study analyzed miRNA expression (miR-16, miR-21, miR-135b, miR-145, and miR-335) in pre- and post-chemoradiation rectal adenocarcinoma tissue and non-neoplastic mucosa in 91 patients treated with neoadjuvant CRT (50.4 Gy) and proctectomy. Two groups were defined: a pathological complete responders group (tumor regression grade—TRG 0) and a pathological incomplete responders group (TRG 1, 2, and 3). Results: miR-21 and miR-135b were upregulated in tumor tissue of incomplete responders comparing with non-neoplastic tissue (p = 0.008 and p < 0.0001, respectively). Multivariate analysis showed significant association between miR-21 in pre-CRT tumor tissue and response, with a 3.67 odds ratio (OR) of incomplete response in patients with higher miR-21 levels (p = 0.04). Although with no significance, patients treated with 5-fluorouracil (5-FU) presented reduced odds of incomplete response compared with those treated with capecitabine (OR = 0.19; 95% confidence interval (CI) 0.03–1.12, p = 0.05). Moreover, significant differences were seen in overall survival (OS) in relation to clinical TNM stage (p = 0.0004), cT (p = 0.0001), presence of distant disease (p = 0.002), mesorectal tumor deposits (p = 0.003), and tumor regression grade (p = 0.04). Conclusion: miR-21 may predict response to CRT in rectal cancer (RC).
KW - biomarkers
KW - chemoradiotherapy response
KW - miR-21
KW - rectal cancer
KW - tumor regression grade
UR - http://www.scopus.com/inward/record.url?scp=85095958151&partnerID=8YFLogxK
U2 - 10.3389/fonc.2020.577653
DO - 10.3389/fonc.2020.577653
M3 - Article
C2 - 33194696
AN - SCOPUS:85095958151
VL - 10
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 577653
ER -