Glycosyltransferase-related Long Non-coding RNA Signature Predicts the Prognosis of Colon Adenocarcinoma

Overview

Journal Front Oncol

Specialty Oncology

Date 2022 Oct 7

PMID 36203430

Authors

Jiawei Zhang

Yinan Wu

Jiayi Mu

Dijia Xin

Luyao Wang

Yili Fan

Suzhan Zhang

Yang Xu

Affiliations

Soon will be listed here.

Abstract

Purpose: Colon adenocarcinoma (COAD) is the most common type of colorectal cancer (CRC) and is associated with poor prognosis. Emerging evidence has demonstrated that glycosylation by long noncoding RNAs (lncRNAs) was associated with COAD progression. To date, however, the prognostic values of glycosyltransferase (GT)-related lncRNAs in COAD are still largely unknown.

Methods: We obtained the expression matrix of mRNAs and lncRNAs in COAD from The Cancer Genome Atlas (TCGA) database. Then, the univariate Cox regression analysis was conducted to identify 33 prognostic GT-related lncRNAs. Subsequently, LASSO and multivariate Cox regression analysis were performed, and 7 of 33 GT-related lncRNAs were selected to conduct a risk model. Gene set enrichment analysis (GSEA) was used to analyze gene signaling pathway enrichment of the risk model. ImmuCellAI, an online tool for estimating the abundance of immune cells, and correlation analysis were used to explore the tumor-infiltrating immune cells in COAD. Finally, the expression levels of seven lncRNAs were detected in colorectal cancer cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

Results: A total of 1,140 GT-related lncRNAs were identified, and 7 COAD-specific GT-related lncRNAs (LINC02381, MIR210HG, AC009237.14, AC105219.1, ZEB1-AS1, AC002310.1, and AC020558.2) were selected to conduct a risk model. Patients were divided into high- and low-risk groups based on the median of risk score. The prognosis of the high-risk group was worse than that of the low-risk group, indicating the good reliability and specificity of our risk model. Additionally, a nomogram based on the risk score and clinical traits was built to help clinical decisions. GSEA showed that the risk model was significantly enriched in metabolism-related pathways. Immune infiltration analysis revealed that five types of immune cells were significantly different between groups, and two types of immune cells were negatively correlated with the risk score. Besides, we found that the expression levels of these seven lncRNAs in tumor cells were significantly higher than those in normal cells, which verified the feasibility of the risk model.

Conclusion: The efficient risk model based on seven GT-related lncRNAs has prognostic potential for COAD, which may be novel biomarkers and therapeutic targets for COAD patients.

Citing Articles

Predictive Significance of Glycosyltransferase-Related lncRNAs in Endometrial Cancer: A Comprehensive Analysis and Experimental Validation.

Shen X, Liu Y, Zhang J, Zhou T, Zhang Q, Dong K ACS Omega. 2025; 10(8):8023-8041.

PMID: 40060793 PMC: 11886429. DOI: 10.1021/acsomega.4c09071.

Integrative approach using network pharmacology, bioinformatics, and experimental methods to explore the mechanism of cantharidin in treating colorectal cancer.

Hou B, Wang X, He Z, Liu H Naunyn Schmiedebergs Arch Pharmacol. 2024; 397(9):6745-6761.

PMID: 38507104 DOI: 10.1007/s00210-024-03041-7.

Prediction of Prognosis and Chemotherapeutic Sensitivity Based on Cuproptosis-Associated lncRNAs in Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma.

Zhou J, Xu L, Zhou H, Wang J, Xing X Genes (Basel). 2023; 14(7).

PMID: 37510286 PMC: 10379127. DOI: 10.3390/genes14071381.

References

Zhang J, Zhou X, Huang D, Luan C, Gu H, Ju M . Development of an Immune-Related Gene Signature for Prognosis in Melanoma. Front Oncol. 2021; 10:602555. PMC: 7874014. DOI: 10.3389/fonc.2020.602555. View

Blanche P, Dartigues J, Jacqmin-Gadda H . Estimating and comparing time-dependent areas under receiver operating characteristic curves for censored event times with competing risks. Stat Med. 2013; 32(30):5381-97. DOI: 10.1002/sim.5958. View

Kopetz S, Guthrie K, Morris V, Lenz H, Magliocco A, Maru D . Randomized Trial of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF-Mutant Metastatic Colorectal Cancer (SWOG S1406). J Clin Oncol. 2020; 39(4):285-294. PMC: 8462593. DOI: 10.1200/JCO.20.01994. View

Ueno D, Kawabe H, Yamasaki S, Demura T, Kato K . Feature selection for RNA cleavage efficiency at specific sites using the LASSO regression model in Arabidopsis thaliana. BMC Bioinformatics. 2021; 22(1):380. PMC: 8299621. DOI: 10.1186/s12859-021-04291-5. View

Fan B, Zhang Q, Wang N, Wang G . LncRNAs, the Molecules Involved in Communications With Colorectal Cancer Stem Cells. Front Oncol. 2022; 12:811374. PMC: 8829571. DOI: 10.3389/fonc.2022.811374. View

Lizardo D, Kuang C, Hao S, Yu J, Huang Y, Zhang L . Immunotherapy efficacy on mismatch repair-deficient colorectal cancer: From bench to bedside. Biochim Biophys Acta Rev Cancer. 2020; 1874(2):188447. PMC: 7886024. DOI: 10.1016/j.bbcan.2020.188447. View

Heagerty P, Lumley T, Pepe M . Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics. 2000; 56(2):337-44. DOI: 10.1111/j.0006-341x.2000.00337.x. View

Bian X, Sun Y, Wang L, Shang Y . ELK1-induced upregulation lncRNA LINC02381 accelerates the osteosarcoma tumorigenesis through targeting CDCA4 via sponging miR-503-5p. Biochem Biophys Res Commun. 2021; 548:112-119. DOI: 10.1016/j.bbrc.2021.02.072. View

Schjoldager K, Narimatsu Y, Joshi H, Clausen H . Global view of human protein glycosylation pathways and functions. Nat Rev Mol Cell Biol. 2020; 21(12):729-749. DOI: 10.1038/s41580-020-00294-x. View

10.

Flum M, Dicks S, Teng Y, Schrempp M, Nystrom A, Boerries M . Canonical TGFβ signaling induces collective invasion in colorectal carcinogenesis through a Snail1- and Zeb1-independent partial EMT. Oncogene. 2022; 41(10):1492-1506. PMC: 8897192. DOI: 10.1038/s41388-022-02190-4. View

11.

Brannon A, Vakiani E, Sylvester B, Scott S, McDermott G, Shah R . Comparative sequencing analysis reveals high genomic concordance between matched primary and metastatic colorectal cancer lesions. Genome Biol. 2014; 15(8):454. PMC: 4189196. DOI: 10.1186/s13059-014-0454-7. View

12.

Vaine C, Soberman R . The CD200-CD200R1 inhibitory signaling pathway: immune regulation and host-pathogen interactions. Adv Immunol. 2014; 121:191-211. PMC: 4617684. DOI: 10.1016/B978-0-12-800100-4.00005-2. View

13.

Almquist D, Ahn D, Bekaii-Saab T . The Role of Immune Checkpoint Inhibitors in Colorectal Adenocarcinoma. BioDrugs. 2020; 34(3):349-362. DOI: 10.1007/s40259-020-00420-3. View

14.

Marisa L, De Reynies A, Duval A, Selves J, Gaub M, Vescovo L . Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. PLoS Med. 2013; 10(5):e1001453. PMC: 3660251. DOI: 10.1371/journal.pmed.1001453. View

15.

Stewart S, Wike J, Kato I, Lewis D, Michaud F . A population-based study of colorectal cancer histology in the United States, 1998-2001. Cancer. 2006; 107(5 Suppl):1128-41. DOI: 10.1002/cncr.22010. View

16.

Chen X, Zhang Z, Ma Y, Su H, Xie P, Ran J . LINC02381 Promoted Cell Viability and Migration via Targeting miR-133b in Cervical Cancer Cells. Cancer Manag Res. 2020; 12:3971-3979. PMC: 7261661. DOI: 10.2147/CMAR.S237285. View

17.

Liu P, Huang H, Qi X, Bian C, Cheng M, Liu L . Hypoxia-Induced LncRNA-MIR210HG Promotes Cancer Progression By Inhibiting HIF-1α Degradation in Ovarian Cancer. Front Oncol. 2021; 11:701488. PMC: 8655245. DOI: 10.3389/fonc.2021.701488. View

18.

Siegel R, Miller K, Fuchs H, Jemal A . Cancer statistics, 2022. CA Cancer J Clin. 2022; 72(1):7-33. DOI: 10.3322/caac.21708. View

19.

Venturi G, Gomes Ferreira I, Pucci M, Ferracin M, Malagolini N, Chiricolo M . Impact of sialyltransferase ST6GAL1 overexpression on different colon cancer cell types. Glycobiology. 2019; 29(10):684-695. DOI: 10.1093/glycob/cwz053. View

20.

Tie J, Cohen J, Wang Y, Christie M, Simons K, Lee M . Circulating Tumor DNA Analyses as Markers of Recurrence Risk and Benefit of Adjuvant Therapy for Stage III Colon Cancer. JAMA Oncol. 2019; 5(12):1710-1717. PMC: 6802034. DOI: 10.1001/jamaoncol.2019.3616. View