Genome-wide RNA-sequencing dataset reveals AC096751.1 sever as a novel prognostic long non-coding RNA and its potential molecular mechanisms in patients with colon adenocarcinoma

Abstract

Objective: Through data analysis, we observed that AC096751.1 is markedly imbalance between colon adenocarcinoma (COAD) cancer and paracancerous tissues. However, the prognostic value and potential molecular mechanism of AC096751.1 in COAD are still unclear. Methods: Whole genome RNA-sequencing datasets of The Cancer Genome Atlas (TCGA) COAD cohort were collected into current study, comprehensive survival analysis and bioinformatics function enrichment analysis approaches were apply to explore the clinical outcome and molecular mechanisms of AC096751.1 in COAD. Results: In current study, we found that AC096751.1 is markedly down-regulated in COAD cancer tissues (log2 fold change =2.303, P<0.0001, false discovery rate <0.0001), and can be serve as a biomarker to distinguish COAD cancer and paracancerous tissues [area under curve=0.9518, 95% confidence interval (CI)=0.9261-0.9776]. Survival analysis suggests that low expression of AC096751.1 is connected with poor clinical outcome of COAD, and can serve as a novel prognostic indicator (log-rank P=0.016, adjusted P=0.005, hazard ratio=0.548, 95% CI=0.360-0.836). Bioinformatics function enrichment analysis suggests that the molecular mechanism of AC096751.1 in COAD may include participation in cell adhesion, cell proliferation, mitogen-activated protein kinase kinase (MAPKK), MAPK, janus-activated kinase-singal transducers and activators of transcriprion cascade, Erk1 and Erk 2 cascade, and nuclear factor-kappa B pathway. Tumor microenvironment and immune infiltration analysis indicates that COAD patients with different AC096751.1 expression have significant variation in tumor immune background. Conclusion: The present study found that AC096751.1 is significantly differentially expressed in COAD and can be serve as a novel prognostic biomarker.

Keywords: AC096751.1; The Cancer Genome Atlas.; colon adenocarcinoma; long non-coding RNA; overall survival.

Figure 1

Expression distribution of AC096751.1 between COAD carcinoma and adjacent tissues. (A) Scatter plot of AC096751.1 expression in COAD carcinoma and adjacent tissues in TCGA cohort; (B) ROC curve of AC096751.1 in distinguish COAD carcinoma and adjacent tissues in TCGA cohort. (C) Scatter plot of AC096751.1 expression in COAD carcinoma and adjacent tissues in Guangxi cohort; (D) ROC curve of AC096751.1 in distinguish COAD carcinoma and adjacent tissues in Guangxi cohort.

Figure 2

Prognostic value of AC096751.1 in COAD. (A) Kaplan-Meier curve of AC096751.1 in COAD; (B) Nomogram of AC096751.1 in COAD.

Figure 3

Joint effect survival analysis of AC096751.1 in COAD. (A) AC096751.1 combined with tumor stage (I, II, III and IV); (B) AC096751.1 combined with tumor stage (I+II and III+IV).

Figure 4

Co-expression interaction network of AC096751.1 in COAD.

Figure 5

Survival analysis of AC096751.1 co-expressed genes in COAD OS. (A) Volcano plot of survival analysis results of AC096751.1 co-expressed genes; (B) Kaplan-Meier curve of DAPK1; (C) Kaplan-Meier curve of EVI5; (D) Kaplan-Meier curve of CRYBA4.

Figure 6

Bar plot of AC096751.1 co-expressed gene functional enrichment analysis results.

Figure 7

GSEA results between high- and low-AC096751.1 expression phenotypes in COAD. (A) mammary stem cell up; (B) signaling by Robo receptors; (C) EZH2 targets up; (D) MAD1 targets dn; (E) oxidative phosphorylation; (F) NADH dehydrogenase complex.

Figure 8

Volcano plot of DEGs between high- and low-AC096751.1 expression phenotypes.

Figure 9

Survival analysis of DEGs between high- and low-AC096751.1 expression phenotypes in COAD OS. (A) Volcano plot of survival analysis results of DEGs; (B) Kaplan-Meier curve of COX8C; (C) Kaplan-Meier curve of PNMA5; (D) Kaplan-Meier curve of PCOLCE2.

Figure 10

Bar plot for functional enrichment analysis results of DEGs between high- and low-AC096751.1 expression phenotypes.

Figure 11

The relationship between AC096751.1 and tumor microenvironment score in COAD. (A) Scatter plot of stromal score and AC096751.1; (B) Scatter plot of immune score and AC096751.1; (C) Scatter plot of ESTIMATE score and AC096751.1.

Figure 12

Immune cell infiltration difference box plot between high- and low-AC096751.1 expression phenotypes in COAD. Notes: *P<0.05, **P<0.01, ***P<0.001.