Authors
Khan, Mairah TYang, Lingjian
More, Elisabet
Irlam-Jones, Joely J
Valentine, Helen R
Hoskin, Peter J
Choudhury, Ananya
West, Catharine M L
Affiliation
Translational Radiobiology Group, Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Christie NHS Foundation Trust Hospital, Manchester M20 4BXIssue Date
2021
Metadata
Show full item recordAbstract
Long non-coding RNAs (lncRNAs) are involved in diverse biological processes, including DNA damage repair, and are of interest as potential biomarkers of radiosensitivity. We investigated whether lncRNA radiosensitivity signatures could be derived for use in cancer patients treated with radiotherapy. Signature development involved radiosensitivity measurements for cell lines and primary tumor samples, and patient outcome after radiotherapy. A 10-lncRNA signature trained on radiosensitivity measurements in bladder cell lines showed a trend towards independent validation. In multivariable analyses, patients with tumors classified as radioresistant by the lncRNA signature had poorer local relapse-free survival (P = 0.065) in 151 patients with muscle-invasive bladder cancer who underwent radiotherapy. An mRNA-based radiosensitivity index signature performed similarly to the lncRNA bladder signature for local relapse-free survival (P = 0.055). Pathway analysis showed the lncRNA signature associated with molecular processes involved in radiation responses. Knockdown of one of the lncRNAs in the signature showed a modest increase in radiosensitivity in one cell line. An alternative approach involved training on primary cervical tumor radiosensitivity or local control after radiotherapy. Both approaches failed to generate a cervix lncRNA radiosensitivity signature, which was attributed to the age of samples in our cohorts. Our work highlights challenges in validating lncRNA signatures as biomarkers in archival tissue from radiotherapy cohorts, but supports continued investigation of lncRNAs for a role in radiosensitivity.Citation
Khan MT, Yang L, More E, Irlam-Jones JJ, Valentine HR, Hoskin P, et al. Developing Tumor Radiosensitivity Signatures Using LncRNAs. Radiat Res. 2021.Journal
Radiation ResearchDOI
10.1667/rade-20-00157.1PubMed ID
33577642Additional Links
https://dx.doi.org/10.1667/rade-20-00157.1Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1667/rade-20-00157.1
Scopus Count
Collections
Related articles
- A three-lncRNA signature predicts overall survival and disease-free survival in patients with esophageal squamous cell carcinoma.
- Authors: Huang GW, Xue YJ, Wu ZY, Xu XE, Wu JY, Cao HH, Zhu Y, He JZ, Li CQ, Li EM, Xu LY
- Issue date: 2018 Feb 6
- Six-long non-coding RNA signature predicts recurrence-free survival in hepatocellular carcinoma.
- Authors: Gu JX, Zhang X, Miao RC, Xiang XH, Fu YN, Zhang JY, Liu C, Qu K
- Issue date: 2019 Jan 14
- A prognostic index based on a fourteen long non-coding RNA signature to predict the recurrence-free survival for muscle-invasive bladder cancer patients.
- Authors: Zhang X, Zhang M, Zhang X, Zhu X, Wang J
- Issue date: 2020 Jul 9
- A novel lncRNA-focus expression signature for survival prediction in endometrial carcinoma.
- Authors: Zhou M, Zhang Z, Zhao H, Bao S, Sun J
- Issue date: 2018 Jan 5
- A potential prognostic lncRNA signature for predicting survival in patients with bladder urothelial carcinoma.
- Authors: Bao Z, Zhang W, Dong D
- Issue date: 2017 Feb 7