ARTICLE
Volume 10,Issue 4
22 November 2024
Comprehensive Bioinformatics Analysis Reveals Kirsten Rat Sarcoma Virus Oncogene (KRAS) as the Potential Biomarker of Esophageal Carcinoma
Muhammad Akram
Show Less
1
Department of Microbiology, King Saud University, Saudi Arabia,
PAR 2024 , 8(6), 209–222;
https://doi.org/10.26689/par.v8i6.8144
© 2024 by the Authors. Licensee Whioce Publishing, Singapore. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract
In the current study, the expression of the Kirsten rat sarcoma virus oncogene (KRAS) in esophageal carcinoma (ESCA) was examined for its medical and therapeutic relevance. ESCA has a 20% five-year survival rate, placing it seventh in the world in terms of overall rate of mortality. GEPIA2, UALCAN, OncoDB, cBioPortal, STRING, DAVID, and TIMER2 databases are among the bioinformatics tools used to conduct this investigation. According to the analysis, KRAS was significantly (P < 0.05) elevated in ESCA samples in contrast to normal tissues, demonstrating that it might play an active role in the proliferation of malignancies. Additionally, the study based on several clinicopathological features showed that KRAS were significantly up-regulated. ESCA patients had a worse overall survival rate (OS) as KRAS was significantly overexpressed. Besides this, the study carried out analyses of drug sensitivity, enrichment, and promoter methylation to inquire about their relationships to KRAS expression in ESCA. The KRAS mutation was demonstrated to have a significant impact on the progression of ESCA via the genetic changes that were observed using cBioPortal. In conclusion, the comprehensive analysis of the findings emphasizes the significance of KRAS up-regulation in the development of ESCA and its potential as a potential biomarker.
References
Bray F, Laversanne M, Sung H, et al., 2024, Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 74(3): 229–263.
Sung H, Ferlay J, Siegel RL, et al., 2021, Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71(3): 209–249.
Rumgay H, Shield K, Charvat H, et al. 2021, Global Burden of Cancer in 2020 Attributable to Alcohol Consumption: A Population-Based Study. The Lancet Oncology, 22(8): 1071–1080.
Grille VJ, Campbell S, Gibbs JF, et al., 2021, Esophageal Cancer: The Rise of Adenocarcinoma over Squamous Cell Carcinoma in the Asian Belt. Journal of Gastrointestinal Oncology, 12(2): 339–349.
GBD 2017 Oesophageal Cancer Collaborators, 2020, The Global, Regional, and National Burden of Oesophageal Cancer and its Attributable Risk Factors in 195 Countries and Territories, 1990–2017: A Systematic Analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol, 5(6): 582–597.
Liu CQ, Ma YL, Qin Q, et al., 2023, Epidemiology of Esophageal Cancer in 2020 and Projections to 2030 and 2040. Thoracic Cancer, 14(1): 3–11.
Simba H, Kuivaniemi H, Abnet CC, et al., 2023, Environmental and Life-style Risk Factors for Esophageal Squamous Cell Carcinoma in Africa: A Systematic Review and Meta-analysis. BMC Public Health, 23(1): 1782.
Huang J, Koulaouzidis A, Marlicz W, et al., 2021, Global Burden, Risk Factors, and Trends of Esophageal Cancer: An Analysis of Cancer Registries from 48 Countries. Cancers, 13(1): 141.
Li J, Xu J, Zheng Y, et al., 2021, Esophageal Cancer: Epidemiology, Risk Factors and Screening. Chinese Journal of Cancer Research, 33(5): 535.
Matsuda S, Takeuchi M, Kawakubo H, et al., 2023, Lymph Node Metastatic Patterns and the Development of Multidisciplinary Treatment for Esophageal Cancer. Diseases of the Esophagus, 36(4): doad006.
Bolger JC, Donohoe CL, Lowery M, et al., 2022, Advances in the Curative Management of Oesophageal Cancer. British Journal of Cancer, 126(5): 706–717.
Sheffels E, Kortum RL, 2021, The Role of Wild-type RAS in Oncogenic RAS Transformation. Genes, 12(5): 662.
Apken LH, Oeckinghaus A, 2021, The RAL Signaling Network: Cancer and Beyond. International Review of Cell and Molecular Biology, 2021(361): 21–105.
Stalnecker CA, Der CJ, 2020, RAS, Wanted Dead or Alive: Advances in Targeting RAS Mutant Cancers. Science Signaling, 13(624): eaay6013.
Fernandez-Medarde A, De Las Rivas J, Santos E, 2021, 40 years of RAS—A Historic Overview. Genes, 12(5): 681.
Timar J, Kashofer K, 2020, Molecular Epidemiology and Diagnostics of KRAS Mutations in Human Cancer. Cancer Metastasis Reviews, 39(4): 1029–1038.
Won Y, Choi E, 2022, Mouse Models of KRAS Activation in Gastric Cancer. Experimental & Molecular Medicine, 54(11): 1793–1798.
Zhou Y, Zeng Z, Li Z, et al., 2024, The Relationship of KRAS Expression with KRAS Status, Prognosis, and Tumor-infiltrated T Lymphocytes in Colorectal Cancer. Therapeutic Advances in Gastroenterology, 2024(17): 17562848241249387.
Pazik M, Zebrowska-Nawrocka M, Wosiak A, et al., 2023, Comprehensive Analysis of the Expression and Clinical Significance of RAS Family Members in Non-Small Cell Lung Cancer Based on Bioinformatics Data and the A549 Cell Line Model. Applied Sciences, 13(1): 166.
Polom K, Das K, Marrelli D, et al., 2019, KRAS Mutation in Gastric Cancer and Prognostication Associated with Microsatellite Instability Status. Pathology Oncology Research, 25(1): 333–340.
Luo J, 2021, KRAS Mutation in Pancreatic Cancer. Seminars in Oncology, 48(1): 10–18.
Tang Z, Kang B, Li C, et al., 2019, GEPIA2: An Enhanced Web Server for Large-scale Expression Profiling and Interactive Analysis. Nucleic Acids Research, 47(1): 556–560.
Chandrashekar DS, Karthikeyan SK, Korla PK, et al., 2022, UALCAN: An Update to the Integrated Cancer Data Analysis Platform. Neoplasia, 2022(25): 18–27.
Mishra A, Shrivastava A, 2020, Prognostic Significance of Sodium Iodide Symporter and Deiodinase Enzymes mRNA Expression in Gastric Cancer. International Journal of Applied and Basic Medical Research, 10(1): 43–48.
Tang G, Cho M, Wang X, 2022, OncoDB: An Interactive Online Database for Analysis of Gene Expression and Viral Infection in Cancer. Nucleic Acids Research, 50(1): 1334–1339.
Bruijn ID, Kundra R, Mastrogiacomo B, et al., 2023, Analysis and Visualization of Longitudinal Genomic and Clinical Data from the AACR Project GENIE Biopharma Collaborative in cBioPortal. Cancer Research, 83(23): 3861–3867.
Szklarczyk D, Gable AL, Lyon D, et al., 2019, STRING v11: Protein-protein Association Networks with Increased Coverage, Supporting Functional Discovery in Genome-wide Experimental Datasets. Nucleic Acids Research, 47(1): 607–613.
Sherman BT, Hao M, Qiu J, et al., 2022, DAVID: A Web Server for Functional Enrichment Analysis and Functional Annotation of Gene Lists (2021 Update). Nucleic Acids Research, 50(1): 216–221.
Li T, Fu J, Zeng Z, et al., 2020, TIMER 2.0 for Analysis of Tumor-infiltrating Immune Cells. Nucleic Acids Research, 48(1): 509–514.
Liu CJ, Hu FF, Xie GY, et al., 2023, GSCA: An Integrated Platform for Gene Set Cancer Analysis at Genomic, Pharmacogenomic and Immunogenomic Levels. Briefings in Bioinformatics, 24(1): bbac558.
Mattei AL, Bailly N, Meissner A, 2022, DNA Methylation: A Historical Perspective. Trends in Genetics, 38(7): 676–707.
Huang RZ, Mao M, Zheng J, et al., 2021, Development of an Immune-related Gene Pairs Index for the Prognosis Analysis of Metastatic Melanoma. Scientific Reports, 11(1): 1253.
Bray F, Laversanne M, Sung H, et al., 2024, Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 74(3): 229–263.
Collaborators GOC, 2020, The Global, Regional, and National Burden of Oesophageal Cancer and its Attributable Risk Factors in 195 Countries and Territories, 1990–2017: A Systematic Analysis for the Global Burden of Disease Study 2017. The Lancet Gastroenterology & Hepatology, 5(6): 582.
Peng Z, Liu XY, Cheng Z, et al., 2021, Comprehensive Analysis of a New Immune-related Prognostic Signature for Esophageal Cancer and its Correlation with Infiltrating Immune Cells and Target Genes. Annals of Translational Medicine, 9(20): 1576.
Chhichholiya Y, Singh HV, Vashistha R, et al., 2024, Deciphering the Role of KRAS Gene in Oncogenesis: Focus on Signaling Pathways, Genetic Alterations in 3’UTR, KRAS specific miRNAs and Therapeutic Interventions. Critical Reviews in Oncology/Hematology, 2024(194): 104250.
Johnson C, Burkhart DL, Haigis KM, 2022, Classification of KRAS-activating Mutations and the Implications for Therapeutic Intervention. Cancer Discovery, 12(4): 913–923.
Kontomanolis EN, Koutras A, Syllaios A, et al., 2020, Role of Oncogenes and Tumor-suppressor Genes in Carcinogenesis: A Review. Anticancer Research, 40(11): 6009–6015.
Iancu IV, Botezatu A, Plesa A, et al., 2020, Alterations of Regulatory Factors and DNA Methylation Pattern in Thyroid Cancer. Cancer Biomarkers, 28(2): 255–268.
Yang J, Xu J, Wang W, et al., 2023, Epigenetic Regulation in the Tumor Microenvironment: Molecular Mechanisms and Therapeutic Targets. Signal Transduction and Targeted Therapy, 8(1): 210.
Kolch W, Berta D, Rosta E, 2023, Dynamic Regulation of RAS and RAS Signaling. The Biochemical Journal, 480(1): 1–23.
Baxter RC, 2023, Signaling Pathways of the Insulin-like Growth Factor Binding Proteins. Endocrine Reviews, 44(5): 753–778.
Share
Back to top
Bio-Byword Scientific Publishing Pty. Ltd.
We are committed to supporting the scientific community by publishing impactful research and fostering effective communication among scientists. We continuously seek ways to accelerate scientific progress while upholding transparency and open dialogue. Our goal is to make knowledge freely and barrier‑free accessible to all.
Contact us: info@bbwpublisher.com
Level 10, 50 Clarence Street Sydney, NSW 2000 Australia