Identification of lncRNA Signature Associated With Pan-Cancer Prognosis

Abstract

Long noncoding RNAs (lncRNAs) have emerged as potential prognostic markers in various human cancers as they participate in many malignant behaviors. However, the value of lncRNAs as prognostic markers among diverse human cancers is still under investigation, and a systematic signature based on these transcripts that related to pan-cancer prognosis has yet to be reported. In this study, we proposed a framework to incorporate statistical power, biological rationale, and machine learning models for pan-cancer prognosis analysis. The framework identified a 5-lncRNA signature (ENSG00000206567, PCAT29, ENSG00000257989, LOC388282, and LINC00339) from TCGA training studies (n=1,878). The identified lncRNAs are significantly associated (all P ≤1.48E-11) with overall survival (OS) of the TCGA cohort (n=4,231). The signature stratified the cohort into low-and high-risk groups with significantly distinct survival outcomes (median OS of 9.84 years versus 4.37 years, log-rank P=1.48E-38) and achieved a time-dependent ROC/AUC of 0.66 at 5 years. After routine clinical factors involved, the signature demonstrated better performance for long-term prognostic estimation (AUC of 0.72). Moreover, the signature was further evaluated on two independent external cohorts (TARGET, n=1,122; CPTAC, n=391; National Cancer Institute) which yielded similar prognostic values (AUC of 0.60 and 0.75; logrank P=8.6E-09 and P=2.7E-06). An indexing system was developed to map the 5-lncRNA signature to prognoses of pan-cancer patients. In silico functional analysis indicated that the lncRNAs are associated with common biological processes driving human cancers. The five lncRNAs, especially ENSG00000206567, ENSG00000257989 and LOC388282 that never reported before, may serve as viable molecular targets common among diverse cancers.

Four Types of RNA Modification Writer-Related lncRNAs Are Effective Predictors of Prognosis and Immunotherapy Response in Serous Ovarian Carcinoma

“…Moreover, Bao et al. found that PCAT29 was expressed in OC and the positive rate of PCAT29 was 82/116; they also identified PCAT29 as a signature associated with prognosis in pan-cancer (including OC) ( 56 ). PR11-508M8.1 was proposed as a biomarker for predicting the risk of papillary thyroid carcinoma relapse ( 57 ).…”

Nine Pyroptosis-Related lncRNAs are Identified as Biomarkers for Predicting the Prognosis and Immunotherapy of Endometrial Carcinoma

“… 28 In a pan-cancer study, a signature based on 5 lncRNAs was found to behave well in predicting survival outcomes of cancers based on the TCGA, TARGET, and National Cancer Institute cohorts. 29 After exploring the lncRNAs in colorectal cancer, HOXA11-AS, MEG3, SLCO4A1-AS1, SPINT1-AS1, and DANCR lncRNAs were discovered strong power for the diagnosis. 30 Four-methylated LncRNAs were considered as biomarkers for predicting the survival of osteosarcoma.…”

Prognostic prediction of clear cell renal cell carcinoma based on lipid metabolism-related lncRNA risk coefficient model

“…With the development of biotechnology, the results of the Human Genome Project show that less than 2% of the nucleic acid sequence is used to encode proteins, and the rest part doesn’t express proteins, which are called non-coding RNAs(ncRNA) ( He et al, 2021 ; Yip et al, 2021 ; Zhou et al, 2021 ). ncRNA was originally thought to be transcriptional noise, but with the advancement of researches, it is been discovered that ncRNA is pivotal for normal development and disease progression ( Bao et al, 2021 ; Chen et al, 2021 ; Smolarz et al, 2021 ). ncRNAs exceeding 200 nt are called lncRNAs.…”