LIU Minling 1, DAI Wei 2, ZHU Mengyuan 1, LI Xueying 1, WEI Min 1, LI Lei 3*, FANG Shuo 1,3*
1Department of Oncology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
2Department of Surgery, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
3Department of Clinical Oncology, The University of Hong Kong, Hong Kong, China
Liu Minling, firstname.lastname@example.org, https://orcid.org/0000-0001-7317-5600.
* Correspondence: LI Lei, email@example.com, FANG Shuo, firstname.lastname@example.org, https://orcid.org/0000-0002-1724-404X.
Article History Received 26 June 2021 Accepted 25 July 2021 Published 30 September 2021
Cite this Article LIU Minling, DAI Wei, ZHU Mengyuan, LI Xueying, WEI Min, LI Lei, FANG Shuo. An 8-lncRNA signature predicts the survival of triple-negative breast cancer patients without germline BRCA1/2 mutation [J].Medical Research, 2021.3(3):15-32, http://dx.doi.org/mrhk/10.6913/MRHK.202109_3(3).0003
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Purpose: TNBC with germline BRCA1/2 mutation (gBRCAm) have higher sensitivity to DNA damaging agents including platinum-based chemotherapy and PARP inhibitors. But the treatment of TNBC without gBRCAm remains challenging. This study aimed to develop a long non-coding RNA (lncRNA) signature of TNBC patients without gBRCAm to improve risk stratification and optimize individualized treatment.
Methods: 98 TNBC patients without gBRCAm were acquired from The Cancer Genome Atlas database. The univariable Cox regression analysis and LASSO Cox regression model were applied to establish an lncRNA signature in the training cohort. Then Kaplan–Meier survival curve and time-dependent ROC curve were used to validate the prognostic ability of the signature. The qPCR assay was performed to confirm the expressions and clinicopathological correlations of two potential lncRNAs HAGLROS and TONSL-AS1 in 30 paired clinical triple-negative breast cancer samples without gBRCAm.
Results: We developed an 8-lncRNA signature in the training cohort including HAGLROS, AL139002.1, AL391244.2, AP000696.1, AL391056.1, AL513304.1, TONSL-AS1 and AL031008.1. Patients with higher risk scores showed significantly worse overall survival compared to those with lower risk scores (P=0.00018 and P =0.0068 respectively). 30 paired specimens of TNBC without gBRCAm in our center showed that two potential lncRNAs HAGLROS and TONSL-AS1 were found frequently overexpressed, and significantly associated with tumor grade and invasion.
Conclusion: We constructed a novel 8-lncRNA signature which significantly associated with the overall survival of TNBC patients without gBRCAm. Among those 8 lncRNAs, HAGLROS and TONSL-AS1 may be potential therapeutic targets which function needed further exploration.
Keywords: Long non-coding RNA, triple-negative breast cancer, germline BRCA1/2 mutation, overall survival, signature