Identification of LncRNA Prognostic Signature Associated With Genomic Instability in Pancreatic Adenocarcinoma

Jinfeng Zhu; Qian Huang; Xingyu Peng; Chen Luo; Sicheng Liu; Zitao Liu; Xun Wu; Hongliang Luo

doi:10.3389/fonc.2022.799475

Identification of LncRNA Prognostic Signature Associated With Genomic Instability in Pancreatic Adenocarcinoma

Front Oncol. 2022 Mar 29:12:799475. doi: 10.3389/fonc.2022.799475. eCollection 2022.

Authors

Jinfeng Zhu^{1

2}, Qian Huang³, Xingyu Peng^{1

2}, Chen Luo¹, Sicheng Liu¹, Zitao Liu¹, Xun Wu¹, Hongliang Luo¹

Affiliations

¹ Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
² Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China.
³ Department of General Practice, The Third Xiangya Hospital, Central South University, Changsha, China.

Abstract

Background: Genomic instability (GI) is a critical feature of cancer which plays a key role in the occurrence and development of pancreatic adenocarcinoma (PAAD). Long non-coding RNA (LncRNA) is an emerging prognostic biomarker because it is involved in regulating GI. Recently, researchers used such GI-related LncRNAs (GILncRNAs) to establish a prognostic signature for patients with cancer and helped in predicting the overall prognosis of the patients. However, it is evident that patients with PAAD still lack such prognostic signature constructed with GILncRNA.

Methods: The present study screened GILncRNAs from 83 patients with PAAD. Prognosis-related GILncRNAs were identified by univariate Cox regression analysis. The correlation coefficients of these GILncRNAs were obtained by multivariate Cox regression analysis and used to construct a signature. The signature in the present study was then assessed through survival analysis, mutation correlation analysis, independent prognostic analysis, and clinical stratification analysis in the training set and validated in the testing as well as all TCGA set. The current study performed external clinical relevance validation of the signature and validated the effect of AC108134.2 in GILncSig on PAAD using in vitro experiments. Finally, the function of GILncRNA signature (GILncSig) dependent on Gene Ontology enrichment analysis was explored and chemotherapeutic drug sensitivity analysis was also performed.

Results: Results of the present study found that a total of 409 GILncRNAs were identified, 5 of which constituted the prognostic risk signature in this study, namely, AC095057.3, AC108134.2, AC124798.1, AL606834.1, and AC104695.4. It was found that the signature of the present study was better than others in predicting the overall survival and applied to patients with PAAD of all ages, genders, and tumor grades. Further, it was noted that the signature of the current study in the GSE102238, was correlated with tumor length, and tumor stage of patients with PAAD. In vitro, functional experiments were used in the present study to validate that AC108134.2 is associated with PAAD genomic instability and progression. Notably, results of the pRRophetic analysis in the current study showed that the high-risk group possessed reverse characteristics and was sensitive to chemotherapy.

Conclusions: In conclusion, it was evident that the GILncSig used in the present study has good prognostic performance. Therefore, the signature may become a potential sensitive biological indicator of PAAD chemotherapy, which may help in clinical decision-making and management of patients with cancer.

Keywords: chemosensitivity; genomic instability; long non-coding RNA; pancreatic adenocarcinoma; prognosis; signature.