Research Paper Volume 12, Issue 3 pp 2626—2646

Screening and identification of genes associated with cell proliferation in cholangiocarcinoma

Li Guo 1, *, , Yaodong Zhang 2, *, , Zibo Yin 1, , Yaya Ji 3, , Guowei Yang 1, , Bowen Qian 1, , Sunjing Li 1, , Jun Wang 1, , Tingming Liang 3, , Changxian Li 2, , Xiangcheng Li 2, ,

  • 1 Department of Bioinformatics, Smart Health Big Data Analysis and Location Services Engineering Lab of Jiangsu Province, School of Geographic and Biologic Information, Nanjing University of Posts and Telecommunications, Nanjing 210023, China
  • 2 Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
  • 3 Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Science, Nanjing Normal University, Nanjing 210023, China
* Equal contribution

received: September 20, 2019 ; accepted: January 12, 2020 ; published: February 10, 2020 ;

https://doi.org/10.18632/aging.102766
How to Cite

Copyright © 2020 Guo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Cholangiocarcinoma (CCA), an aggressive tumor with poor prognosis, is a malignant cancer with increasing incidence and mortality rates. It is important to survey crucial genes in CCA to find and design potential drug targets, especially for those genes associated with cell proliferation that is a key biological process in tumorgenesis. Herein, we surveyed genes associated with cell proliferation via a comprehensive pan-cancer analysis. Candidate genes were further analyzed using multiple approaches, including cross-analysis from diverse molecular levels, examination of potential function and interactions, and additional experimental validation. We primarily screened 15 potential genes based on 11 validated genes, and these 26 genes were further examined to delineate their biological functions and potential roles in cancer treatment. Several of them were involved synthetically lethal genetic interactions, especially for RECQL4, TOP2A, MKI67 and ASPM, indicating their potential roles in drug design and cancer treatment. Further experimental validation indicated that some genes were significantly upregulated in several cancer cell lines, implying their important roles in tumorigenesis. Our study identifies some genes associated with cell proliferation, which may be potential future targets in molecular targeted therapy.

Abbreviations

ACC: adrenocortical carcinoma; BLCA: bladder urothelial carcinoma; BRCA: breast invasive carcinoma; CCA: Cholangiocarcinoma; CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma; CGC: cancer gene census; CHOL: cholangiocarcinoma; COAD: colon adenocarcinoma; DAVID: Database for Annotation, Visualization and Integrated Discovery; DLBC: lymphoid neoplasm diffuse large B-cell lymphoma; ESCA: esophageal carcinoma; GBM: glioblastoma multiforme; GDSC: Genomics of Drug Sensitivity in Cancer; GO: gene ontology; HNSC: head and neck squamous cell carcinoma; HRG: histidine-rich glycoprotein; KEGG: Kyoto Encyclopedia of Genes and Genomes; KICH: kidney chromophobe; KIRC: Kidney renal clear cell carcinoma; KIRP: kidney renal papillary cell carcinoma; LAML: acute myeloid leukemia; LIHC: liver hepatocellular carcinoma; LGG: brain Lower grade glioma; LUAD: lung adenocarcinoma; LUSC: lung squamous cell carcinoma; MESO: Mesothelioma; OV: ovarian serous cystadenocarcinoma; PAAD: pancreatic adenocarcinoma; PCPG: pheochromocytoma and paraganglioma; PRAD: prostate adenocarcinoma; READ: rectum adenocarcinoma; SARC: sarcoma; SKCM: skin cutaneous melanoma; STAD: stomach adenocarcinoma; TCGA: The Cancer Genome Atlas; TGCT: testicular germ cell tumors; THCA: thyroid carcinoma; THYM: thymoma; TSG: tumor suppressor gene; UCEC: uterine corpus endometrial carcinoma; UCS: uterine carcinosarcoma; UVM: uveal melanoma.