Keywords
FAM3A expression
Bioinformatics analysis
Biomarker
Submitted : 2024-07-10
Accepted : 2024-07-25
Published : 2024-08-09
Abstract
Liver hepatocellular cancer (LIHC) is positioned as the third cancer with the highest mortalities worldwide, and high mortalities are associated with late diagnosis and recurrence. This study advances bioinformatics analysis of FAM3A expression in LIHC to evaluate its potential as a prognostic, diagnostic and therapeutic biomarker. Bioinformatics tools such as UALCAN, GEPIA2, KM plotter, TIMER2 and cBioPortal are employed to conduct analysis. Initially, the expression analysis revealed up-regulation of FAM3A in LIHC based on various variables. Further, the study observed that FAM3A methylation regulates expression as variation in methylation level of FAM3A was assessed in LIHC. Moreover, this over-expression of FAM3A results in poor overall survival (OS) in LIHC patients. All of these proposed that FAM3A has a role in the progression and development of LIHC. While examined association of FAM3A expression and infiltration level of CD8+ T cells in LIHC patients using TIMER2 revealed that FAM3A has a positive correlation with purity in LIHC that highlights the molecular landscape. Analysis of genetic alteration revealed minute role of FAM3A in LIHC still provides valuable insight. Overall, our findings reveal that FAM3A has potential as diagnostic, therapeutic and prognostic biomarkers in LIHC.
References
Upadhyay A, 2021, Cancer: An Unknown Territory, Rethinking Before Going Ahead. Genes & Diseases, 8(5): 655–661.
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.
Ma X, Yu H, 2006, Cancer Issue: Global Burden of Cancer. The Yale Journal of Biology and Medicine, 79(3–4): 85.
Kaur H, Bhalla S, Raghava GPS, 2019, Classification of Early and Late Stage Liver Hepatocellular Carcinoma Patients from Their Genomics and Epigenomics Profiles. PLOS ONE, 14(9).
Bray F, Ferlay J, Soerjomataram I, et al., 2018, Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68(6): 394–424.
Herceg Z, Paliwal A, 2011, Epigenetic Mechanisms in Hepatocellular Carcinoma: How Environmental Factors Influence the Epigenome. Mutation Research, 727(3): 55–61.
Yang JD, Roberts LR, 2010, Hepatocellular Carcinoma: A Global View. Nature Reviews Gastroenterology & Hepatology, 7(8): 448–458.
Siegel RL, Miller KD, Jemal A, 2019, Cancer Statistics. CA: A Cancer Journal for Clinicians, 69(1): 7–34.
Wang S, Liu Y, Feng Y, et al., 2019, A Review on Curability of Cancers: More Efforts for Novel Therapeutic Options Are Needed. Cancers, 11(11): 1782.
Chen L, Yuan L, Wang Y, et al., 2017, Co-expression Network Analysis Identified FCER1G in Association with Progression and Prognosis in Human Clear Cell Renal Cell Carcinoma. International Journal of Biological Sciences, 13(11): 1361.
Sun J, Zhang Z, Cai J, et al., 2024, Identification of Hub Genes in Liver Hepatocellular Carcinoma Based on Weighted Gene Co-expression Network Analysis. Biochemical Genetics.
Poon D, Anderson BO, Chen LT, et al., 2009, Management of Hepatocellular Carcinoma in Asia: Consensus Statement from the Asian Oncology Summit 2009. The Lancet Oncology, 10(11): 1111–1118.
Balogh J, Victor III D, Asham EH, et al., 2016, Hepatocellular Carcinoma: A Review. Journal of Hepatocellular Carcinoma, 2016(3): 41–53.
Bruix J, da Fonseca LG, Reig M, 2019, Insights into the Success and Failure of Systemic Therapy for Hepatocellular Carcinoma. Nature Reviews Gastroenterology & Hepatology, 16(10): 617–630.
Yang W, Wang J, Chen Z, et al., 2017, NFE2 Induces miR-423-5p to Promote Gluconeogenesis and Hyperglycemia by Repressing the Hepatic FAM3A-ATP-Akt Pathway. Diabetes, 66(7): 1819–1832.
Wang C, Chi Y, Li J, et al., 2014, FAM3A Activates PI3K p110Alpha/Akt Signaling to Ameliorate Hepatic Gluconeogenesis and Lipogenesis. Hepatology, 59(5): 1779–1790.
Zhang X, Yang W, Wang J, et al., 2018, FAM3 Gene Family: A Promising Therapeutical Target for NAFLD and Type 2 Diabetes. Metabolism, 81: 71–82.
Jia S, Chen Z, Li J, et al., 2014, FAM3A Promotes Vascular Smooth Muscle Cell Proliferation and Migration and Exacerbates Neointima Formation in Rat Artery After Balloon Injury. Journal of Molecular and Cellular Cardiology, 74: 173–182.
Wang C, Chi Y, Li J, et al., 2014, FAM3A Activates PI3K p110Alpha/Akt Signaling to Ameliorate Hepatic Gluconeogenesis and Lipogenesis. Hepatology, 59(5): 1779–90.
Sala D, Cunningham TJ, Stec MJ, et al., 2019, The Stat3-Fam3a Axis Promotes Muscle Stem Cell Myogenic Lineage Progression by Inducing Mitochondrial Respiration. Nature Communications, 10(1): 1796.
Yang W, Wang J, Chen Z, et al., 2017, NFE2 Induces miR-423-5p to Promote Gluconeogenesis and Hyperglycemia by Repressing the Hepatic FAM3A-ATP-Akt Pathway. Diabetes, 66(7): 1819–32.
Yang J, Zhang LJ, Wang F, et al., 2019, Molecular Imaging of Diabetes and Diabetic Complications: Beyond Pancreatic Beta-cell Targeting. Advanced Drug Delivery Reviews, 139: 32–50.
Jin ES, Beddow SA, Malloy CR, et al., 2013, Hepatic Glucose Production Pathways After Three Days of a High-Fat Diet. Metabolism, 62(1): 152–162.
Chi Y, Li J, Li N, et al., 2017, FAM3A Enhances Adipogenesis of 3T3-L1 Preadipocytes via Activation of ATP-P2 Receptor-Akt Signaling Pathway. Oncotarget, 8(28): 45862.
Song Q, Gou WL, Zhang R, et al., 2016, FAM3A Attenuates ER Stress-Induced Mitochondrial Dysfunction and Apoptosis via CHOP-Wnt Pathway. Neurochemistry International, 94: 82–89.
Li J, Yan H, Xiang R, et al., 2022, ATP Secretion and Metabolism in Regulating Pancreatic Beta Cell Functions and Hepatic Glycolipid Metabolism. Frontiers in Physiology, 13.
Dong QT, Ma DD, Gong Q, et al., 2023, FAM3 Family Genes Are Associated with Prognostic Value of Human Cancer: A Pan-Cancer Analysis. Sci Rep, 13(1): 15144.
Chandrashekar DS, Bashel B, Balasubramanya SAH, et al., 2017, UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia, 19(8): 649–658.
Chen C, Wang X, Huang S, et al., 2017, Prognostic Roles of Notch Receptor mRNA Expression in Human Ovarian Cancer. Oncotarget, 8(20): 32731.
Tang Z, Li C, Kang B, et al., 2017, GEPIA: A Web Server for Cancer and Normal Gene Expression Profiling and Interactive Analyses. Nucleic Acids Research, 45(W1): W102.
Gao J, Aksoy BA, Dogrusoz U, et al., 2013, Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal. Science Signal, 6(269): pl1.
Li T, Fu J, Zeng Z, et al., 2020, TIMER2.0 for Analysis of Tumor-Infiltrating Immune Cells. Nucleic Acids Research, 48(W1): W514.
Zhou WH, Li YF, Al-Aroomi MA, et al., 2022, Overexpression of Fibronectin 1 Promotes Cancer Progression and Associated with M2 Macrophages Polarization in Head and Neck Squamous Cell Carcinoma Patients. International Journal of General Medicine, 15: 5027–5042.
Wan S, He Y, Zhang B, et al., 2022, Overexpression of CDCA8 Predicts Poor Prognosis and Promotes Tumor Cell Growth in Prostate Cancer. Frontiers in Oncology, 12.
Moarii M, Boeva V, Vert JP, et al., 2015, Changes in Correlation Between Promoter Methylation and Gene Expression in Cancer. BMC Genomics, 16(1): 873.
Wang K, Dai R, Xia Y, et al., 2022, Spatiotemporal Specificity of Correlated DNA Methylation and Gene Expression Pairs Across Different Human Tissues and Stages of Brain Development. Epigenetics, 17(10): 1110–1127.
Pandya PH, Murray ME, Pollok KE, et al., 2016, The Immune System in Cancer Pathogenesis: Potential Therapeutic Approaches. Journal of Immunology Research, 2016(1): 4273943.
Aran D, Sirota M, Butte AJ, 2015, Systematic Pan-Cancer Analysis of Tumour Purity. Nature Communications, 6(1): 8971.
Sarkar S, Horn G, Moulton K, et al., 2013, Cancer Development, Progression, and Therapy: An Epigenetic Overview. International Journal of Molecular Sciences, 14(10): 21087–21113.
Su C, Yang JC, Rong Z, et al., 2023, Identification of CCDC115 as an Adverse Prognostic Biomarker in Liver Cancer Based on Bioinformatics and Experimental Analyses. Heliyon, 9(9): e19233.
Cancer Genome Atlas Research Network, 2017, Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma. Cell, 169(7): 1327–1341.
Xu W, Liang M, Zhang Y, et al., 2019, Endothelial FAM3A Positively Regulates Post-Ischaemic Angiogenesis. EBioMedicine, 43: 32–42.
Song Q, Gao Q, Chen T, et al., 2021, FAM3A Ameliorates Brain Impairment Induced by Hypoxia–Ischemia in Neonatal Rat. Cellular and Molecular Neurobiology, 43(1): 1–14.
Xiang R, Chen J, Li S, et al., 2020, VSMC-Specific Deletion of FAM3A Attenuated Ang II-Promoted Hypertension and Cardiovascular Hypertrophy. Circulation Research, 126(12):1746–59.