Prognostic Significance and Therapeutic Potential of BUB1B, CCNB2, DLGAP5, and ZWINT in Hepatocellular Carcinoma: An Analysis Based on GEO and TCGA Databases
Abstract
five-year survival rate. Despite advancements in liver surgery, tumor recurrence and metastasis are prevalent, necessitating new biomarkers
for prognosis and therapeutic targeting. This study aimed to identify and evaluate the prognostic significance of differentially expressed genes
(DEGs) in HCC using data from GEO and TCGA databases. Methods: Gene expression profiles from multiple GEO datasets (GSE17548,
GSE45436, GSE55092, GSE60502, and GSE84402) and the TCGA database were analyzed. DEGs between tumor and adjacent normal tissues were identified using the Limma package. The prognostic significance of these genes was assessed through univariate and multivariate
Cox regression analyses, Kaplan-Meier survival analysis, and receiver operating characteristic (ROC) curve analysis. Functional enrichment
and immune infiltration analyses were conducted using Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA), and the CIBERSORT
algorithm. Results: Twenty-four DEGs, including BUB1B, CCNB2, DLGAP5, and ZWINT, were identified. These genes were significantly
overexpressed in HCC tissues compared to normal tissues. High expression levels of BUB1B, CCNB2, DLGAP5, and ZWINT were associated with poor overall survival and progression-free survival. Functional analysis revealed their involvement in key biological processes and
pathways. Immune infiltration analysis indicated significant correlations between these gene expressions and various immune cell types,
suggesting their roles in the tumor immune microenvironment. Drug sensitivity analysis identified potential therapeutic compounds targeting
these genes. Conclusion: BUB1B, CCNB2, DLGAP5, and ZWINT are significantly overexpressed in HCC and serve as potential prognostic
biomarkers and therapeutic targets. Their high expression levels correlate with poor prognosis and reduced efficacy of immunotherapy, highlighting their clinical relevance in HCC management. Future studies should further investigate these genes at the protein level and through
functional experiments to validate their roles in HCC progression and treatment.
Keywords
Full Text:
PDFReferences
[1] BROWN Z J, TSILIMIGRAS D I, RUFF S M, et al. Management of Hepatocellular Carcinoma: A Review [J]. JAMA surgery, 2023,
158(4): 410-20.
[2] DE LOPE C R, TREMOSINI S, FORNER A, et al. Management of HCC [J]. Journal of hepatology, 2012, 56 Suppl 1: S75-87.
[3] CAUCHY F, SOUBRANE O, BELGHITI J. Liver resection for HCC: patient's selection and controversial scenarios [J]. Best practice &
research Clinical gastroenterology, 2014, 28(5): 881-96.
[4] THABUT D, KUDO M. Treatment of portal hypertension in patients with HCC in the era of Baveno VII [J]. Journal of hepatology,
2023, 78(3): 658-62.
[5] MELIS M, DIAZ G, KLEINER D E, et al. Viral expression and molecular profiling in liver tissue versus microdissected hepatocytes in
hepatitis B virus-associated hepatocellular carcinoma [J]. Journal of translational medicine, 2014, 12: 230.
[6] WANG Y H, CHENG T Y, CHEN T Y, et al. Plasmalemmal Vesicle Associated Protein (PLVAP) as a therapeutic target for treatment of
hepatocellular carcinoma [J]. BMC cancer, 2014, 14: 815.
[7] WANG H W, HSIEH T H, HUANG S Y, et al. Forfeited hepatogenesis program and increased embryonic stem cell traits in young hepatocellular carcinoma (HCC) comparing to elderly HCC [J]. BMC genomics, 2013, 14: 736.
[8] YILDIZ G, ARSLAN-ERGUL A, BAGISLAR S, et al. Genome-wide transcriptional reorganization associated with senescence-toimmortality switch during human hepatocellular carcinogenesis [J]. PloS one, 2013, 8(5): e64016.
[9] TAYLOR S S, HA E, MCKEON F. The human homologue of Bub3 is required for kinetochore localization of Bub1 and a Mad3/Bub1-
related protein kinase [J]. J Cell Biol, 1998, 142(1).
[10] YAMAMOTO Y, MATSUYAMA H, CHOCHI Y, et al. Overexpression of BUBR1 is associated with chromosomal instability in bladder
cancer [J]. Cancer genetics and cytogenetics, 2007, 174(1): 42-7.
[11] WAN X, YEUNG C, KIM S Y, et al. Identification of FoxM1/Bub1b signaling pathway as a required component for growth and survival
of rhabdomyosarcoma [J]. Cancer research, 2012, 72(22): 5889-99.
[12] CHEN H, LEE J, KLJAVIN N M, et al. Requirement for BUB1B/BUBR1 in tumor progression of lung adenocarcinoma [J]. Genes &
cancer, 2015, 6(3-4): 106-18.
[13] QIU J, ZHANG S, WANG P, et al. BUB1B promotes hepatocellular carcinoma progression via activation of the mTORC1 signaling
pathway [J]. Cancer medicine, 2020, 9(21): 8159-72.
[14] LI H, TIAN X, WANG P, et al. MicroRNA-582-3p negatively regulates cell proliferation and cell cycle progression in acute myeloid
leukemia by targeting cyclin B2 [J]. Cellular & molecular biology letters, 2019, 24: 66.
[15] HUANG J, ZHOU H, DIAO Y, et al. Hsa_circ_0000285 knockdown inhibits the progression of hepatocellular carcinoma by sponging
miR-582-3p to regulate CCNB2 expression [J]. Human & experimental toxicology, 2022, 41: 9603271221115400.
[16] TANG N, DOU X, YOU X, et al. Pan-cancer analysis of the oncogenic role of discs large homolog associated protein 5 (DLGAP5) in
human tumors [J]. Cancer cell international, 2021, 21(1): 457.
[17] LIAO W, LIU W, YUAN Q, et al. Silencing of DLGAP5 by siRNA significantly inhibits the proliferation and invasion of hepatocellular
carcinoma cells [J]. PloS one, 2013, 8(12): e80789.
[18] LIN Y T, CHEN Y, WU G, et al. Hec1 sequentially recruits Zwint-1 and ZW10 to kinetochores for faithful chromosome segregation and
spindle checkpoint control [J]. Oncogene, 2006, 25(52): 6901-14.
[19] LI H N, ZHENG W H, DU Y Y, et al. ZW10 interacting kinetochore protein may serve as a prognostic biomarker for human breast cancer: An integrated bioinformatics analysis [J]. Oncology letters, 2020, 19(3): 2163-74.
[20] YANG L, HAN N, ZHANG X, et al. ZWINT: A potential therapeutic biomarker in patients with glioblastoma correlates with cell proliferation and invasion [J]. Oncology reports, 2020, 43(6): 1831-44.
DOI: http://dx.doi.org/10.70711/pmr.v3i7.9420
Refbacks
- There are currently no refbacks.
