Unique metastasis‐associated lncRNA signature optimizes prediction of tumor relapse in lung adenocarcinoma

Abstract

Background Local relapses and metastases are primary causes of death in lung cancer patients. In the present study, we aimed to develop a prognostic signature based on metastasis‐associated lncRNAs in patients with lung adenocarcinoma (LUAD). Methods Firstly, the potential metastasis‐associated lncRNAs were identified by analyzing high‐throughput data from The Cancer Genome Atlas (TCGA), and based on which, an lncRNA signature was constructed for prediction of relapse in LUAD patients using Cox proportional hazards regression analysis. Moreover, the prognostic performance of the lncRNA signature was evaluated using Kaplan‐Meier survival analysis, time‐dependent receiver operating characteristic (ROC) curve and Cox analysis, respectively. In addition, the potential metastasis‐associated function of these six lncRNAs was confirmed by lncRNA over‐expression or depletion and in vitro transwell assays in LUAD cells. Results An lncRNA signature consisting of six most important prognostic factors (LINC01819, ZNF649‐AS1, HNF4A‐AS1, FAM222A‐AS1, LINC02323 and LINC00672) was developed. The signature was an independent predictor for patients' relapse‐free survival (RFS), which could provide higher tumor relapse prediction capability compared with the TNM staging system at three years and five years, respectively (P = 0.0209 and P = 0.0468). Furthermore, the combination of this lncRNA signature and TNM stage had better prognostic value than TNM stage alone at three and five years, respectively (P = 0.0006 and P = 0.0096). Additionally, all the lncRNAs of the signature had a regulatory role in the LUAD cell mobility. Conclusions This novel six‐lncRNA signature had considerable prognostic value for prediction of relapse in LUAD patients. Key points Significant findings of the studyThe unique metastasis‐associated lncRNA signature was related to tumor metastasis and prognosis in LUAD patients. What this study addsThis signature had considerable prognostic value for prediction of relapse in LUAD patients.

Development and Validation of an Immune-Related lncRNA Signature for Predicting the Prognosis of Hepatocellular Carcinoma

“…Hence, identifying effective lncRNAs to predict the prognosis of cancer patients has gradually attracted various levels of scientific research. Moreover, researchers have explored many lncRNA predictive models to determine the prognosis of tumor patients including liver cancer, pancreatic cancer, lung cancer, esophageal cancer, colorectal cancer, breast cancer, among others ( Gu et al, 2018 , 2019 ; Zhao et al, 2018 ; Liu et al, 2019 ; Ma and Deng, 2019 ; Zhou et al, 2019 ; Shen et al, 2020 ; Zhang et al, 2020 ; Zheng et al, 2020 ). A study by Ma found that four lncRNA signature can effectively distinguish high-risk and low-risk patients in liver cirrhosis and liver cancer patients thereby accurately predict the prognosis of liver cancer patients ( Ma and Deng, 2019 ).…”

“…Therefore, the search for immune-related lncRNA in liver cancer may provide a new target for HCC treatment. Current researches have explored many lncRNA signatures associated with tumor prognosis ( Gu et al, 2018 ; Zhao et al, 2018 ; Zhou et al, 2019 ; Li et al, 2020 ; Shen et al, 2020 ; Zhang et al, 2020 ; Zheng et al, 2020 ). However, fewer lncRNA signatures have been identified in liver cancer since many studies focus on microRNAs and mRNAs.…”

Novel long noncoding RNA LINC02323 promotes cell growth and migration of ovarian cancer via TGF‐β receptor 1 by miR‐1343‐3p

“…OS and DFS of lncRNA LINC02323 high expressions were lower than those of lncRNA LINC02323 low expression, which is consistent with the LINC02323‐mediated metastasis of ovarian cancer. Zhang et al showed that LINC01819 signature had a regulatory role in the lung adenocarcinom cell mobility 16 …”

Novel long non‐coding RNA LINC02323 promotes epithelial‐mesenchymal transition and metastasis via sponging miR‐1343‐3p in lung adenocarcinoma

“…[16][17][18] Our previous study has shown that six lncRNAs, including LINC02323, are associated with metastasis and prognosis of LUAD. 19 Herein, we hypothesized that LINC02323-miRNA-target pathway might participate in the process of EMT and metastasis of LUAD. However, the exact mechanisms and pathways still remain unclear.…”