Identification and Validation of Three Autophagy-Related Long Noncoding RNAs as Prognostic Signature in Cholangiocarcinoma

Abstract

Cholangiocarcinoma (CCA) is featured by common occurrence and poor prognosis. Autophagy is a biological process that has been extensively involved in the progression of tumors. Long noncoding RNAs (lncRNAs) have been discovered to be critical in diagnosing and predicting various tumors. It may be valuable to elaborate autophagy-related lncRNAs (ARlncRNAs) in CCA, and indeed, there are still few studies concerning the role of ARlncRNAs in CCA. Here, a prognostic ARlncRNA signature was constructed to predict the survival outcome of CCA patients. Through identification, three differentially expressed ARlncRNAs (DEARlncRNAs), including CHRM3.AS2, MIR205HG, and LINC00661, were screened and were considered predictive signatures. Furthermore, the overall survival (OS) of patients with high-risk scores was significantly lower than that of patients with low scores. Interestingly, the risk score was an independent factor for the OS of patients with CCA. Moreover, receiver operating characteristic (ROC) curve analysis showed that the screened and constructed prognosis signature for 1 year (AUC = 0.884), 3 years (AUC =0.759), and 5 years (AUC = 0.788) presented a high score of accuracy in predicting OS of CCA patients. Gene set enrichment analysis (GSEA) revealed that the three DEARlncRNAs were significantly enriched in CCA-related signaling pathways, including “pathways of basal cell carcinoma”, “glycerolipid metabolism”, etc. Quantitative real-time PCR (qRT-PCR) showed that expressions of CHRM3.AS2, MIR205HG, and LINC00661 were higher in CCA tissues than those in normal tissues, similar to the trends detected in the CCA dataset. Furthermore, Pearson’s analysis reported an intimate correlation of the risk score with immune cell infiltration, indicating a predictive value of the signature for the efficacy of immunotherapy. In addition, the screened lncRNAs were found to have the ability to modulate the expression of mRNAs by interacting with miRNAs based on the established lncRNA-miRNA-mRNA network. In conclusion, our study develops a novel nomogram with good reliability and accuracy to predict the OS of CCA patients, providing a significant guiding value for developing tailored therapy for CCA patients.

Effects of 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione on autophagy and the PI3K/AKT/mTOR signaling pathway in human cholangiocarcinoma QBC939 cells

“…Cells were incubated overnight in a CO 2 incubator at 37 ℃. The control group and experimental group with different concentrations of DMDD (5,10,20,40, and 80 μM/L) were set up and incubated for 24, 48, and 72 h. Then, 10 μL CCK8 solution was added and incubation was continued for 2 h. The absorbance value of each well was read at 450 nm on an enzyme standard instrument. Cell viability (%) = [optical density (OD) of experimental group − OD of control group]/(OD of control group − OD of blank group) × 100%, and the halfinhibitory concentration (IC50) of DMDD on QBC939 cells was calculated.…”

“…Studies have reported that impaired autophagy regulation is closely associated with carcinogenesis, metastasis and poor prognosis of bile duct cells and can be an effective anticancer target. Three autophagy-associated long-stranded non-coding RNAs have been identified as prognostic features of bile duct cancer (20,21).…”

Construction of endothelial cell‐related and autophagy‐related prognostic models for hepatocellular carcinoma based on single‐cell data

“…They function as a double‐edged sword in carcinogenesis and metastasis. For example, autophagy works as a tumor‐suppressive process that avoids persistent tissue damage and cell injury, particularly during the early stages of carcinogenesis 8 . Numerous types of cancer, including HCC, strongly correlate with inflammation and tumor growth and have an unfavorable prognosis 9 .…”

“…For example, autophagy works as a tumor-suppressive process that avoids persistent tissue damage and cell injury, particularly during the early stages of carcinogenesis. 8 Numerous types of cancer, including HCC, strongly correlate with inflammation and tumor growth and have an unfavorable prognosis. 9 Previous studies have proven that inhibiting autophagy increases the inflammatory response, hence boosting the growth of cancer.…”

An Independent Prognostic Model Based on Ten Autophagy-Related Long Noncoding RNAs in Pancreatic Cancer Patients

“…Sun et al determined the prognostic signature based on autophagy-related lncRNAs (ATRlncRNAs); this signature might potentially be used for targeted therapy and evaluation of the prognosis of colon cancer patients [ 17 , 18 ]. Liu et al investigated the clinical role of ATRlncRNAs in cholangiocarcinoma and demonstrated its potential for the personalization of cholangiocarcinoma treatment [ 19 ]. Deng et al proposed a six-ATRlncRNA signature that might be helpful for individualized therapy and PC patient assessment.…”