A Novel Autophagy-Related IncRNAs Signature for Prognostic Prediction and Clinical Value in Patients With Pancreatic Cancer

Zhengdong Deng; Xiangyu Li; Yuanxin Shi; Yun Lu; Wei Yao; Jianming Wang

doi:10.3389/fcell.2020.606817

A Novel Autophagy-Related IncRNAs Signature for Prognostic Prediction and Clinical Value in Patients With Pancreatic Cancer

Front Cell Dev Biol. 2020 Dec 15:8:606817. doi: 10.3389/fcell.2020.606817. eCollection 2020.

Authors

Zhengdong Deng¹, Xiangyu Li¹, Yuanxin Shi¹, Yun Lu¹, Wei Yao², Jianming Wang^{1

3}

Affiliations

¹ Department of Biliary and Pancreatic Surgery/Cancer Research Center Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Oncology Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ Affiliated Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, China.

Abstract

Autophagy is an important bioprocess throughout the occurrence and development of cancer. However, the role of autophagy-related lncRNAs in pancreatic cancer (PC) remains obscure. In the study, we identified the autophagy-related lncRNAs (ARlncRNAs) and divided the PC patients from The Cancer Genome Atlas into training and validation set. Firstly, we constructed a signature in the training set by the least absolute shrinkage and selection operator penalized cox regression analysis and the multivariate cox regression analysis. Then, we validated the independent prognostic role of the risk signature in both training and validation set with survival analysis, receiver operating characteristic analysis, and Cox regression. The nomogram was established to demonstrate the predictive power of the signature. Moreover, high risk scores were significantly correlated to worse outcomes and severe clinical characteristics. The Pearson's analysis between risk scores with immune cells infiltration, tumor mutation burden, and the expression level of chemotherapy target molecules indicated that the signature could predict efficacy of immunotherapy and targeted therapy. Next, we constructed an lncRNA-miRNA-mRNA regulatory network and identified several potential small molecule drugs in the Connectivity Map (CMap). What's more, quantitative real-time PCR (qRT-PCR) analysis showed that serum LINC01559 could serve as a diagnostic biomarker. In vitro analysis showed inhibition of LINC01559 suppressed PC cell proliferation, migration, and invasion. Additionally, silencing LINC01559 suppressed gemcitabine-induced autophagy and promoted the sensitivity of PC cells to gemcitabine. In conclusion, we identified a novel ARlncRNAs signature with valuable clinical utility for reliable prognostic prediction and personalized treatment of PC patients. And inhibition of LINC01559 might be a novel strategy to overcome chemoresistance.

Keywords: LINC01559; autophagy-related lncRNA signature; chemoresistance; pancreatic cancer; prognostic prediction.