Identification and Validation of Six Autophagy-related Long Non-coding RNAs as Prognostic Signature in Colorectal Cancer

Abstract

Colorectal cancer (CRC) is a commonly occurring tumour with poor prognosis. Autophagy-related long non-coding RNAs (lncRNAs) have received much attention as biomarkers for cancer prognosis and diagnosis. However, few studies have focused on their prognostic predictive value specifically in CRC. This research aimed to construct a robust autophagy-related lncRNA prognostic signature for CRC. Autophagy-related lncRNAs from The Cancer Genome Atlas database were screened using univariate Cox, LASSO, and multivariate Cox regression analyses, and the resulting key lncRNAs were used to establish a prognostic risk score model. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to detect the expression of several lncRNAs in cancer tissues from CRC patients and in normal tissues adjacent to the cancer tissues. A prognostic signature comprising lncRNAs AC125603.2, LINC00909, AC016876.1, MIR210HG, AC009237.14, and LINC01063 was identified in patients with CRC. A graphical nomogram based on the autophagy-related lncRNA signature was developed to predict CRC patients' 1-, 3-, and 5-year survival. Overall survival in patients with low risk scores was significantly better than in those with high risk scores (P < 0.0001); a similar result was obtained in an internal validation sample. The nomogram was shown to be suitable for clinical use and gave correct predictions. The 1-and 3-year values of the area under the receiver operating characteristic curve were 0.797 and 0.771 in the model sample, and 0.656 and 0.642 in the internal validation sample, respectively. The C-index values for the verification samples and training samples were 0.756 (95% CI = 0.668-0.762) and 0.715 (95% CI = 0.683-0.829), respectively. Gene set enrichment analysis showed that the six autophagy-related lncRNAs were greatly enriched in CRC-related signalling pathways, including p53 and VEGF signalling. The qRT-PCR results showed that the expression of lncRNAs in CRC was higher than that in adjacent tissues, consistent with the expression trends of lncRNAs in the CRC data set. In summary, we established a signature of six autophagy-related lncRNAs that could effectively guide clinical prediction of prognosis in patients with CRC. This lncRNA signature has significant clinical implications for improving the prediction of outcomes and, with further prospective validation, could be used to guide tailored therapy for CRC patients.

A Novel Immune-Related lncRNA Signature predict the Immune Landscape and Prognosis for Head and Neck Squamous Cell Carcinoma

“…In this study, some of the irlncRNAs in the process of modeling that have been already identi ed play an important role in malignant phenotypes of various cancer types, such as LINC01063 [24,25], HOXC-AS1 [26,27], LINC02454 [28,29] and SCAT1 [30]. Furthermore, previous reports have shown that LINC00460 [31], C5orf66-AS1 [32] and TMPO-AS1 [33] are associated with prognosis and treatment outcomes in HNSCC.…”

Prognostic Significance of Autophagy-Relevant Gene Markers in Colorectal Cancer

“…According to the KM survival analysis, the autophagy-associated genes EPHB2, NOL3, and SNAI1 in the prognostic model were statistically significant (p < 0.05). EPHB2 encodes the receptor tyrosine kinase transmembrane glycoprotein family member EPHB2, which engages in lots of cellular processes including movement, division, and differentiation ( 27 ). EPHB2 functions in the gastrointestinal homeostasis and is an essential factor regulating the classification of mature epithelial cells ( 28 ).…”

“…Studies in human breast cancer have shown that the expression of EPHB2 can induce the increase of ATG5/12 and LC3II, thereby inducing autophagy ( 26 ). Based on experimental results, Kandouz and colleagues propose that EPHB2 may affect autophagy via the ERK1/2 and PI3K pathways ( 27 , 30 ). Moreover, they observed LC3 accumulation and transformation from LC3I to LC3II in EPHB2-upregulated cells.…”

“…This is consistent with the relationship between the low expression of EPHB2 and the poor prognosis of CRC in our survival analysis. EPHB2 is a tumor suppressor that affects the progression of CRC by acting on autophagy ( 27 ).…”

Over Fifty Years of Life, Death, and Cannibalism: A Historical Recollection of Apoptosis and Autophagy

“…In a recent study, Du et al identified autophagy-related genes whose differential expressions are linked to breast tumors and constructed autophagy-related gene signatures with great prognostic value [422]. In addition, autophagy-related long non-coding RNAs (lncRNAs) have been identified as signatures for cancer prognosis and treatment targets, especially in breast, lung, and colorectal cancer [423][424][425][426][427][428][429][430][431]. Moreover, autophagy-related non-coding RNAs have also contributed to diagnosing and treating cardiovascular diseases [432,433].…”