Prognostic Biomarkers of Pancreatic Cancer Identified Based on a Competing Endogenous RNA Regulatory Network

Overview

Journal Transl Cancer Res

Specialty Oncology

Date 2022 Dec 16

PMID 36523322

Authors

Yuanxu Qu

Jiongdi Lu

Wentong Mei

Yuchen Jia

Chunjing Bian

Yixuan Ding

Yulin Guo

Feng Cao

Fei Li

Affiliations

Soon will be listed here.

Abstract

Background: Pancreatic cancer is an insidious and heterogeneous malignancy with poor prognosis that is often locally unresectable. Therefore, determining the underlying mechanisms and effective prognostic indicators of pancreatic cancer may help optimize clinical management. This study was conducted to develop a prognostic model for pancreatic cancer based on a competing endogenous RNA (ceRNA) network.

Methods: We obtained transcriptomic data and corresponding clinicopathological information of pancreatic cancer samples from The Cancer Genome Atlas (TCGA) database (training set). Based on the ceRNA interaction network, we screened candidate genes to build prediction models. Univariate Cox regression analysis was performed to screen for genes associated with prognosis, and least absolute shrinkage and selection operator (LASSO) regression analysis was conducted to construct a predictive model. A receiver operating characteristic (ROC) curve was drawn, and the C-index was calculated to evaluate the accuracy of the prediction model. Furthermore, we downloaded transcriptomic data and related clinical information of pancreatic cancer samples from the Gene Expression Omnibus database (validation set) to evaluate the robustness of our prediction model.

Results: Eight genes (, , , , , , , and ) were used to construct the prediction model, which was confirmed as an independent predictor for evaluating the prognosis of patients with pancreatic cancer through univariate and multivariate Cox regression analysis. By plotting the decision curve, we found that the risk score model is an independent predictor has the greatest impact on survival compared to pathological stage and targeted molecular therapy.

Conclusions: An eight-gene prediction model was constructed for effectively and independently predicting the prognosis of patients with pancreatic cancer. These eight genes identified show potential as diagnostic and therapeutic targets.

Citing Articles

Circulating Cell-Free Nucleic Acids as Biomarkers for Diagnosis and Prognosis of Pancreatic Cancer.

Marin A, Sanchuki H, Namur G, Uno M, Zanette D, Aoki M Biomedicines. 2023; 11(4).

PMID: 37189687 PMC: 10136269. DOI: 10.3390/biomedicines11041069.

References

Abou Khouzam R, Rao S, Venkatesh G, Zeinelabdin N, Buart S, Meylan M . An Eight-Gene Hypoxia Signature Predicts Survival in Pancreatic Cancer and Is Associated With an Immunosuppressed Tumor Microenvironment. Front Immunol. 2021; 12:680435. PMC: 8173254. DOI: 10.3389/fimmu.2021.680435. View

Collisson E, Bailey P, Chang D, Biankin A . Molecular subtypes of pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2019; 16(4):207-220. DOI: 10.1038/s41575-019-0109-y. View

Tay Y, Rinn J, Pandolfi P . The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014; 505(7483):344-52. PMC: 4113481. DOI: 10.1038/nature12986. View

Bailey P, Chang D, Nones K, Johns A, Patch A, Gingras M . Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016; 531(7592):47-52. DOI: 10.1038/nature16965. View

Zhang T, Wang Y, Dong Y, Liu L, Han Y, Wang H . Identification of Novel Diagnostic Biomarkers in Prostate Adenocarcinoma Based on the Stromal-Immune Score and Analysis of the WGCNA and ceRNA Network. Dis Markers. 2022; 2022:1909196. PMC: 8783709. DOI: 10.1155/2022/1909196. View

Li X, Li Z, Liu P, Ai S, Sun F, Hu Q . Novel CircRNAs in Hub ceRNA Axis Regulate Gastric Cancer Prognosis and Microenvironment. Front Med (Lausanne). 2021; 8:771206. PMC: 8606568. DOI: 10.3389/fmed.2021.771206. View

Li J, Jin Q, Huang F, Tang Z, Huang J . Effects of Rab27A and Rab27B on Invasion, Proliferation, Apoptosis, and Chemoresistance in Human Pancreatic Cancer Cells. Pancreas. 2017; 46(9):1173-1179. DOI: 10.1097/MPA.0000000000000910. View

Wang L, Cao C, Ma Q, Zeng Q, Wang H, Cheng Z . RNA-seq analyses of multiple meristems of soybean: novel and alternative transcripts, evolutionary and functional implications. BMC Plant Biol. 2014; 14:169. PMC: 4070088. DOI: 10.1186/1471-2229-14-169. View

Barros-Silva J, Linn D, Steiner I, Guo G, Ali A, Pakula H . Single-Cell Analysis Identifies LY6D as a Marker Linking Castration-Resistant Prostate Luminal Cells to Prostate Progenitors and Cancer. Cell Rep. 2018; 25(12):3504-3518.e6. PMC: 6315111. DOI: 10.1016/j.celrep.2018.11.069. View

10.

Luo P, Yang X, Huang S, Feng S, Ou Z . Syntenin overexpression in human lung cancer tissue and serum is associated with poor prognosis. BMC Cancer. 2020; 20(1):159. PMC: 7045730. DOI: 10.1186/s12885-020-6653-6. View

11.

Rawla P, Sunkara T, Gaduputi V . Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors. World J Oncol. 2019; 10(1):10-27. PMC: 6396775. DOI: 10.14740/wjon1166. View

12.

Wong M, Jiang J, Liang M, Fang Y, Yeung M, Sung J . Global temporal patterns of pancreatic cancer and association with socioeconomic development. Sci Rep. 2017; 7(1):3165. PMC: 5466634. DOI: 10.1038/s41598-017-02997-2. View

13.

Barrett T, Suzek T, Troup D, Wilhite S, Ngau W, Ledoux P . NCBI GEO: mining millions of expression profiles--database and tools. Nucleic Acids Res. 2004; 33(Database issue):D562-6. PMC: 539976. DOI: 10.1093/nar/gki022. View

14.

Wang L, Jiang F, Xia X, Zhang B . LncRNA FAL1 promotes carcinogenesis by regulation of miR-637/NUPR1 pathway in colorectal cancer. Int J Biochem Cell Biol. 2018; 106:46-56. DOI: 10.1016/j.biocel.2018.09.015. View

15.

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

16.

Lin H, Dong B, Qi L, Wei Y, Zhang Y, Cai X . Inhibitory Smads suppress pancreatic stellate cell activation through negative feedback in chronic pancreatitis. Ann Transl Med. 2021; 9(5):384. PMC: 8033383. DOI: 10.21037/atm-20-4282. View

17.

Mayama A, Takagi K, Suzuki H, Sato A, Onodera Y, Miki Y . OLFM4, LY6D and S100A7 as potent markers for distant metastasis in estrogen receptor-positive breast carcinoma. Cancer Sci. 2018; 109(10):3350-3359. PMC: 6172070. DOI: 10.1111/cas.13770. View

18.

Zhou W, Ding X, Jin P, Li P . miR-6838-5p Affects Cell Growth, Migration, and Invasion by Targeting GPRIN3 via the Wnt/β-Catenin Signaling Pathway in Gastric Cancer. Pathobiology. 2020; 87(6):327-337. DOI: 10.1159/000511691. View

19.

Ma C, Kang W, Yu L, Yang Z, Ding T . AUNIP Expression Is Correlated With Immune Infiltration and Is a Candidate Diagnostic and Prognostic Biomarker for Hepatocellular Carcinoma and Lung Adenocarcinoma. Front Oncol. 2020; 10:590006. PMC: 7756081. DOI: 10.3389/fonc.2020.590006. View

20.

Singh P, Srinivasan R, Wig J, Radotra B . A study of Smad4, Smad6 and Smad7 in Surgically Resected Samples of Pancreatic Ductal Adenocarcinoma and Their Correlation with Clinicopathological Parameters and Patient Survival. BMC Res Notes. 2011; 4:560. PMC: 3268768. DOI: 10.1186/1756-0500-4-560. View