CDCA3 is a Prognostic Biomarker for Cutaneous Melanoma and is Connected with Immune Infiltration

Overview

Journal Front Oncol

Specialty Oncology

Date 2023 Jan 30

PMID 36713580

Authors

Tianhao Li

Liquan Wang

Nanze Yu

Ang Zeng

Jiuzuo Huang

Xiao Long

Affiliations

Soon will be listed here.

Abstract

Introduction: Dysregulation of cell cycle progression (CCP) is a trait that distinguishes cancer from other diseases. In several cancer types, CCP-related genes serve as the primary risk factor for prognosis, but their role in cutaneous melanoma remains unclear.

Methods: Data from cutaneous melanoma patients were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Using a Wilcoxon test, the level of CCP-related gene expression in cutaneous melanoma patient tissues was compared to that in normal skin tissues. Logistic analysis was then utilized to calculate the connection between the CCP-related genes and clinicopathological variables. The important functions of the CCP-related genes were further investigated using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and single-sample Gene Set Enrichment Analysis (ssGSEA). Univariate and multivariate Cox analyses and Kaplan-Meier analysis were used to estimate the association between CCP-related genes and prognosis. In addition, using Cox multivariate analysis, a nomogram was constructed to forecast the influence of CCP-related genes on survival rates.

Results: High expression of CCP-related genes was associated with TNM stage, age, pathological grade, and Breslow depth (P < 0.05). Multivariate analysis demonstrated that CCP-related genes were an independent factor in overall survival and disease-specific survival. High levels of gene expression originating from CCP were shown by GSEA to trigger DNA replication, the G1-S specific transcription factor, the mitotic spindle checkpoint, and the cell cycle. There was a negative association between CCP-related genes and the abundance of innate immune cells. Finally, we revealed that knockdown of cell division cycle-associated gene 3 (CDCA3) significantly suppressed the proliferation and migration ability of cutaneous melanoma cells.

Conclusion: According to this study, CCP-related genes could serve as potential biomarkers to assess the prognosis of cutaneous melanoma patients and are crucial immune response regulators.

Citing Articles

Prognostic significance and immune landscape of a cell cycle progression-related risk model in bladder cancer.

Tuo Z, Lin Y, Zhang Y, Gao L, Yu D, Wang J Discov Oncol. 2024; 15(1):160.

PMID: 38735911 PMC: 11089032. DOI: 10.1007/s12672-024-01008-x.

References

Zhang Z, Zhou H, Liu Y, Ren J, Wang J, Sang Q . Anti-PD1 antibody enhances the anti-tumor efficacy of MUC1-MBP fusion protein vaccine via increasing Th1, Tc1 activity and decreasing the proportion of MDSC in the B16-MUC1 melanoma mouse model. Int Immunopharmacol. 2021; 101(Pt A):108173. DOI: 10.1016/j.intimp.2021.108173. View

Gerami P, Cook R, Wilkinson J, Russell M, Dhillon N, Amaria R . Development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. Clin Cancer Res. 2015; 21(1):175-83. DOI: 10.1158/1078-0432.CCR-13-3316. View

Li C, Liu T, Wang J, Yu S, Chen Y, Fang F . Hydroxysteroid 11-Beta Dehydrogenase 1 Overexpression with Copy-Number Gain and Missense Mutations in Primary Gastrointestinal Stromal Tumors. J Clin Med. 2018; 7(11). PMC: 6262574. DOI: 10.3390/jcm7110408. View

Tripp M, Watson M, Balk S, Swetter S, Gershenwald J . State of the science on prevention and screening to reduce melanoma incidence and mortality: The time is now. CA Cancer J Clin. 2016; 66(6):460-480. PMC: 5124531. DOI: 10.3322/caac.21352. View

Cooperberg M, Simko J, Cowan J, Reid J, Djalilvand A, Bhatnagar S . Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort. J Clin Oncol. 2013; 31(11):1428-34. DOI: 10.1200/JCO.2012.46.4396. View

Ita M, Wang J, Fanning N, Kaar G, Lim C, Redmond H . Plasma circulating cell free messenger RNA as a potential biomarker of melanoma. Acta Oncol. 2021; 60(9):1201-1209. DOI: 10.1080/0284186X.2021.1928749. View

Buchbinder E, Flaherty K . Biomarkers in Melanoma: Lessons from Translational Medicine. Trends Cancer. 2017; 2(6):305-312. DOI: 10.1016/j.trecan.2016.05.003. View

Hui Y, Leng J, Jin D, Liu D, Wang G, Wang Q . A Cell Cycle Progression-Derived Gene Signature to Predict Prognosis and Therapeutic Response in Hepatocellular Carcinoma. Dis Markers. 2021; 2021:1986159. PMC: 8553501. DOI: 10.1155/2021/1986159. View

Zhang X, Chen Q, Li Y, Chen H, Jiang Q, Hu Q . N-myc Downstream-Regulated Gene 1 (NDRG1) Regulates Vascular Endothelial Growth Factor A (VEGFA) and Malignancies in Glioblastoma Multiforme (GBM). Biomed Res Int. 2022; 2022:3233004. PMC: 9262576. DOI: 10.1155/2022/3233004. View

10.

Evan G, Vousden K . Proliferation, cell cycle and apoptosis in cancer. Nature. 2001; 411(6835):342-8. DOI: 10.1038/35077213. View

11.

Yoshida K . Cell-cycle-dependent regulation of the human and mouse Tome-1 promoters. FEBS Lett. 2005; 579(6):1488-92. DOI: 10.1016/j.febslet.2005.01.055. View

12.

Feigelson H, Teras L, Diver W, Tang W, Patel A, Stevens V . Genetic variation in candidate obesity genes ADRB2, ADRB3, GHRL, HSD11B1, IRS1, IRS2, and SHC1 and risk for breast cancer in the Cancer Prevention Study II. Breast Cancer Res. 2008; 10(4):R57. PMC: 2575528. DOI: 10.1186/bcr2114. View

13.

Marchetti M, Coit D, Dusza S, Yu A, McLean L, Hu Y . Performance of Gene Expression Profile Tests for Prognosis in Patients With Localized Cutaneous Melanoma: A Systematic Review and Meta-analysis. JAMA Dermatol. 2020; 156(9):953-962. PMC: 7391179. DOI: 10.1001/jamadermatol.2020.1731. View

14.

Shannon A, Wood C, Straker 3rd R, Miura J, Ming M, Elenitsas R . Age and Mitogenicity are Important Predictors of Sentinel Lymph Node Metastasis in T1a Melanoma. Ann Surg Oncol. 2021; 28(9):4777-4779. DOI: 10.1245/s10434-021-09929-5. View

15.

Garg M, Couturier D, Nsengimana J, Fonseca N, Wongchenko M, Yan Y . Tumour gene expression signature in primary melanoma predicts long-term outcomes. Nat Commun. 2021; 12(1):1137. PMC: 7893180. DOI: 10.1038/s41467-021-21207-2. View

16.

Johansson I, Tempel D, Dwarkasing J, Rentroia-Pacheco B, Mattsson J, Ny L . Validation of a clinicopathological and gene expression profile model to identify patients with cutaneous melanoma where sentinel lymph node biopsy is unnecessary. Eur J Surg Oncol. 2021; 48(2):320-325. DOI: 10.1016/j.ejso.2021.11.010. View

17.

Chang X, Ma J, Xue X, Wang G, Yan T, Su L . DNMT family induces down-regulation of NDRG1 DNA methylation and clinicopathological significance in gastric cancer. PeerJ. 2021; 9:e12146. PMC: 8450010. DOI: 10.7717/peerj.12146. View

18.

Hsu C, Lee T, Lin M, Liao Y, Liau J, Sheen Y . Risk factors for lymphatic and hematogenous metastasis after diagnosis of cutaneous Melanoma in Taiwan. J Formos Med Assoc. 2022; 121(9):1823-1831. DOI: 10.1016/j.jfma.2022.02.018. View

19.

Matthews H, Bertoli C, de Bruin R . Cell cycle control in cancer. Nat Rev Mol Cell Biol. 2021; 23(1):74-88. DOI: 10.1038/s41580-021-00404-3. View

20.

Trager M, Geskin L, Samie F, Liu L . Biomarkers in melanoma and non-melanoma skin cancer prevention and risk stratification. Exp Dermatol. 2020; 31(1):4-12. DOI: 10.1111/exd.14114. View