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LncRNAs Associated with Chemoradiotherapy Response and Prognosis in Locally Advanced Rectal Cancer

BACKGROUND: There are only limited studies on the long non-coding RNAs (lncRNAs) associated with neoadjuvant chemoradiotherapy (NCRT) response and prognosis of locally advanced rectal cancer (LARC) patients. This study identified lncRNAs associated with NCRT response and prognosis in CRC patients an...

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Autores principales: Zhang, Yiyi, Guan, Bingjie, WU, Yong, Du, Fan, Zhuang, Jinfu, Yang, Yuanfeng, Guan, Guoxian, Liu, Xing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636753/
https://www.ncbi.nlm.nih.gov/pubmed/34866926
http://dx.doi.org/10.2147/JIR.S334096
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author Zhang, Yiyi
Guan, Bingjie
WU, Yong
Du, Fan
Zhuang, Jinfu
Yang, Yuanfeng
Guan, Guoxian
Liu, Xing
author_facet Zhang, Yiyi
Guan, Bingjie
WU, Yong
Du, Fan
Zhuang, Jinfu
Yang, Yuanfeng
Guan, Guoxian
Liu, Xing
author_sort Zhang, Yiyi
collection PubMed
description BACKGROUND: There are only limited studies on the long non-coding RNAs (lncRNAs) associated with neoadjuvant chemoradiotherapy (NCRT) response and prognosis of locally advanced rectal cancer (LARC) patients. This study identified lncRNAs associated with NCRT response and prognosis in CRC patients and explored their potential predictive mechanisms. METHODS: The study subjected the LncRNA expression profiles from our previous gene chip data to LASSO and identified a four-lncRNA signature that predicted NCRT response and prognosis. A Cox regression model was subsequently performed to identify the prognostic risk factors. The function of LINC00909, the lncRNA with the most powerful predictive ability, was finally identified in vivo and in vitro using CRC cell lines. RESULTS: A comparison of the relative lncRNA expression of NCRT-responsive and non-responsive patients revealed four hub lncRNAs: DBET, LINC00909, FLJ33534, and HSD52 with AUC = 0.68, 0.73, 0.73, and 0.70, respectively (all p < 0.05). COX regression analysis further demonstrated that DBET, LINC00909 and FLJ33534 were associated with the DFS in CRC patients. The expression of the four lncRNAs was also significant in LARC patients who had not undergone NCRT (all p < 0.05). A risk score model was subsequently constructed based on the results of the multivariate COX analysis and used to predict NCRT response and prognosis in the CRC and LARC patients. The expression and prognosis of DBET, LINC00909 and FLJ33534 in the CRC tissues were further validated in the R2 platform and Oncomine database. Notably, overexpression of the LINC00909 increased the cell line resistance to the 5-FU and radiotherapy in vivo and in vitro. CONCLUSION: DBET, LINC00909, and FLJ33534 are potential novel biomarkers for predicting NCRT response and prognosis in CRC patients. In particular, LINC00909 is an effective oncogene in CRC that could be used as a novel therapeutic target to enhance NCRT response.
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spelling pubmed-86367532021-12-02 LncRNAs Associated with Chemoradiotherapy Response and Prognosis in Locally Advanced Rectal Cancer Zhang, Yiyi Guan, Bingjie WU, Yong Du, Fan Zhuang, Jinfu Yang, Yuanfeng Guan, Guoxian Liu, Xing J Inflamm Res Original Research BACKGROUND: There are only limited studies on the long non-coding RNAs (lncRNAs) associated with neoadjuvant chemoradiotherapy (NCRT) response and prognosis of locally advanced rectal cancer (LARC) patients. This study identified lncRNAs associated with NCRT response and prognosis in CRC patients and explored their potential predictive mechanisms. METHODS: The study subjected the LncRNA expression profiles from our previous gene chip data to LASSO and identified a four-lncRNA signature that predicted NCRT response and prognosis. A Cox regression model was subsequently performed to identify the prognostic risk factors. The function of LINC00909, the lncRNA with the most powerful predictive ability, was finally identified in vivo and in vitro using CRC cell lines. RESULTS: A comparison of the relative lncRNA expression of NCRT-responsive and non-responsive patients revealed four hub lncRNAs: DBET, LINC00909, FLJ33534, and HSD52 with AUC = 0.68, 0.73, 0.73, and 0.70, respectively (all p < 0.05). COX regression analysis further demonstrated that DBET, LINC00909 and FLJ33534 were associated with the DFS in CRC patients. The expression of the four lncRNAs was also significant in LARC patients who had not undergone NCRT (all p < 0.05). A risk score model was subsequently constructed based on the results of the multivariate COX analysis and used to predict NCRT response and prognosis in the CRC and LARC patients. The expression and prognosis of DBET, LINC00909 and FLJ33534 in the CRC tissues were further validated in the R2 platform and Oncomine database. Notably, overexpression of the LINC00909 increased the cell line resistance to the 5-FU and radiotherapy in vivo and in vitro. CONCLUSION: DBET, LINC00909, and FLJ33534 are potential novel biomarkers for predicting NCRT response and prognosis in CRC patients. In particular, LINC00909 is an effective oncogene in CRC that could be used as a novel therapeutic target to enhance NCRT response. Dove 2021-11-27 /pmc/articles/PMC8636753/ /pubmed/34866926 http://dx.doi.org/10.2147/JIR.S334096 Text en © 2021 Zhang et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Zhang, Yiyi
Guan, Bingjie
WU, Yong
Du, Fan
Zhuang, Jinfu
Yang, Yuanfeng
Guan, Guoxian
Liu, Xing
LncRNAs Associated with Chemoradiotherapy Response and Prognosis in Locally Advanced Rectal Cancer
title LncRNAs Associated with Chemoradiotherapy Response and Prognosis in Locally Advanced Rectal Cancer
title_full LncRNAs Associated with Chemoradiotherapy Response and Prognosis in Locally Advanced Rectal Cancer
title_fullStr LncRNAs Associated with Chemoradiotherapy Response and Prognosis in Locally Advanced Rectal Cancer
title_full_unstemmed LncRNAs Associated with Chemoradiotherapy Response and Prognosis in Locally Advanced Rectal Cancer
title_short LncRNAs Associated with Chemoradiotherapy Response and Prognosis in Locally Advanced Rectal Cancer
title_sort lncrnas associated with chemoradiotherapy response and prognosis in locally advanced rectal cancer
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636753/
https://www.ncbi.nlm.nih.gov/pubmed/34866926
http://dx.doi.org/10.2147/JIR.S334096
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