Identification of Immune-Related Feature Genes in Ovarian Cancer Using Bioinformatics and Analysis of Immune Cell Infiltration
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Keywords

Ovarian cancer
Immune cells
Bioinformatics
Genes

DOI

10.26689/otd.v2i4.9278

Submitted : 2024-12-04
Accepted : 2024-12-19
Published : 2025-01-03

Abstract

Objective: To identify immune-related feature genes in ovarian cancer through bioinformatics analysis and perform immune-related investigations, which hold significant value for the early diagnosis and prevention of ovarian cancer. Methods: Bioinformatics analysis was utilized to identify immune-related feature genes in ovarian cancer. The GSE18520 and GSE40595 datasets were downloaded from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/) based on the gene expression comprehensive database, and the corresponding platform’s chip probe information was retrieved. GSE18520 served as the training set, and GSE40595 served as the validation set. A total of 2660 immune response genes (IRGs) were obtained from the ImmPort database (https://www.immport.org/home). Immune genes were screened and analyzed for feature genes using the “limma” package of R (4.2.1) software, and the results were visualized in a heat map. LASSO regression analysis and ssGSEA analysis were conducted to investigate the distribution of immune cell infiltration. Changes in regression coefficients of different genes in the model were also analyzed. Results: Five key genes—CLEC4M, DEFB1, LCN2, PTH2R, and LGALS2—were identified, and the correlation between these key genes and immune cells was analyzed. Conclusion: The findings indicate that CLEC4M, DEFB1, LCN2, PTH2R, and LGALS2 are significantly associated with various immune cell types, suggesting that these genes may regulate immune cell behavior and influence disease progression. This bioinformatics study provides a foundation for potential therapeutic targets in ovarian cancer; however, further clinical and experimental studies are required to validate the findings.

References

Kujawa KA, Lisowska KM, 2015, Rak Jajnika – Od Biologii do Kliniki [Ovarian Cancer – From Biology to Clinic]. Postępy Higieny i Medycyny Doświadczalnej, 69: 1275–1290.

Rooth C, 2013, Ovarian Cancer: Risk Factors, Treatment and Management. British Journal of Nursing, 22(17): S23–30.

Ledermann JA, 2016, PARP Inhibitors in Ovarian Cancer. Annals of Oncology, 27(Suppl 1): i40–i44.

Kossaï M, Leary A, Scoazec JY, et al., 2018, Ovarian Cancer: A Heterogeneous Disease. Pathobiology, 85(1–2): 41–49.

Schwarz RF, Ng CK, Cooke SL, et al., 2015, Spatial and Temporal Heterogeneity in High-Grade Serous Ovarian Cancer: A Phylogenetic Analysis. PLoS Medicine, 12(2): e1001789.

Wang Y, Wang Z, Zhang Z, et al., 2023, Burden of Ovarian Cancer in China from 1990 to 2030: A Systematic Analysis and Comparison with the Global Level. Frontiers in Public Health, 11: 1136596.

Cortez AJ, Tudrej P, Kujawa KA, et al., 2018, Advances in Ovarian Cancer Therapy. Cancer Chemother Pharmacol, 81(1): 17–38.

Yang C, Xia BR, Zhang ZC, et al., 2020, Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant. Frontiers in Immunology, 11: 577869.

Jäger N, 2022, Bioinformatics Workflows for Clinical Applications in Precision Oncology. Seminars in Cancer Biology, 84: 103–112.

Canzoneri R, Lacunza E, Abba MC, 2019, Genomics and Bioinformatics as Pillars of Precision Medicine in Oncology. Medicina (B Aires), 79(Spec 6/1): 587–592.

Liang Y, Lin F, Huang Y, 2022, Identification of Biomarkers Associated with Diagnosis of Osteoarthritis Patients Based on Bioinformatics and Machine Learning. Journal of Immunology Research, 2022: 5600190.

Wu X, Qin K, Iroegbu CD, et al., 2022, Genetic Analysis of Potential Biomarkers and Therapeutic Targets in Ferroptosis from Coronary Artery Disease. Journal of Cell Molecular Medicine, 26(8): 2177–2190.

Huang J, Zhang J, Wang F, et al., 2022, Comprehensive Analysis of Cuproptosis-Related Genes in Immune Infiltration and Diagnosis in Ulcerative Colitis. Frontiers in Immunology, 13: 1008146.

Liu H, Yu Z, Liu Y, et al., 2023, Investigation of Diagnostic and Prognostic Value of CLEC4M of Non-Small Cell Lung Carcinoma Associated with Immune Microenvironment. International Journal of General Medicine, 16: 1317–1332.

Yu Q, Gao K, 2020, CLEC4M Overexpression Inhibits Progression and is Associated with a Favorable Prognosis in Hepatocellular Carcinoma. Molecular Medicine Reports, 22(3): 2245–2252.

Ling YM, Chen JY, Guo L, et al., 2017, β-Defensin 1 Expression in HCV Infected Liver/Liver Cancer: An Important Role in Protecting HCV Progression and Liver Cancer Development. Scientific Reports, 7(1): 13404.

Alvarez AH, Velazquez MM, Montes EPO, 2018, Human β-Defensin 1 Update: Potential Clinical Applications of the Restless Warrior. International Journal of Biochemistry and Cell Biology, 104: 133–137.

Wang D, Li X, Jiao D, et al., 2023, LCN2 Secreted by Tissue-Infiltrating Neutrophils Induces the Ferroptosis and Wasting of Adipose and Muscle Tissues in Lung Cancer Cachexia. Journal of Hematology Oncology, 16(1): 30.

Lemecha M, Chalise JP, Takamuku Y, et al., 2022, Lcn2 Mediates Adipocyte-Muscle-Tumor Communication and Hypothermia in Pancreatic Cancer Cachexia. Molecular Metabolism, 66: 101612.

Bao Y, Yan Z, Shi N, et al., 2024, LCN2: Versatile Players in Breast Cancer. Biomedicine & Pharmacotherapy, 171: 116091.

Huang Z, Rui X, Yi C, et al., 2023, Silencing LCN2 Suppresses Oral Squamous Cell Carcinoma Progression by Reducing EGFR Signal Activation and Recycling. Journal of Experimental & Clinical Cancer Research, 42(1): 60.

Zhao H, Ding F, Zheng G, 2020, LncRNA TMPO-AS1 Promotes LCN2 Transcriptional Activity and Exerts Oncogenic Functions in Ovarian Cancer. FASEB Journal, 34(9): 11382–11394.

Cho H, Kim JH, 2009, Lipocalin2 Expressions Correlate Significantly with Tumor Differentiation in Epithelial Ovarian Cancer. Journal of Histochemistry and Cytochemistry, 57(5): 513–521.

Dobolyi A, Dimitrov E, Palkovits M, et al., 2012, The Neuroendocrine Functions of the Parathyroid Hormone 2 Receptor. Frontiers in Endocrinology (Lausanne), 3: 121.

Wang X, Cheng X, Zhao L, et al., 2021, Molecular Insights into Differentiated Ligand Recognition of the Human Parathyroid Hormone Receptor 2. Proceedings of the National Academy of Sciences of the United States of America, 118(32): e2101279118.

Zhang L, Wu X, Fan X, et al., 2023, MUM1L1 as a Tumor Suppressor and Potential Biomarker in Ovarian Cancer: Evidence from Bioinformatics Analysis and Basic Experiments. Combinatorial Chemistry & High Throughput Screening, 26(14): 2487–2501.

Xiaowei W, Tong L, Yanjun Q, et al., 2022, PTH2R is Related to Cell Proliferation and Migration in Ovarian Cancer: A Multi-Omics Analysis of Bioinformatics and Experiments. Cancer Cell International, 22(1): 148.

Negedu MN, Duckworth CA, Yu LG, 2022, Galectin-2 in Health and Diseases. International Journal of Molecular Sciences, 24(1): 341.

Ji P, Gong Y, Jin ML, et al., 2022, In Vivo Multidimensional CRISPR Screens Identify Lgals2 as an Immunotherapy Target in Triple-Negative Breast Cancer. Science Advances, 8(26): eabl8247.

Chetry M, Bhandari A, Feng R, et al., 2022, Overexpression of Galectin2 (LGALS2) Predicts a Better Prognosis in Human Breast Cancer. American Journal of Translational Research, 14(4): 2301–2316.

Li H, Yu L, Zhang X, et al., 2022, Exploring the Molecular Mechanisms and Shared Gene Signatures between Rheumatoid Arthritis and Diffuse Large B Cell Lymphoma. Frontiers in Immunology, 13: 1036239.

Xu D, Guo L, Zhang S, et al., 2022, LGALS2 Suppresses the Progression of Papillary Thyroid Carcinoma by Regulating the PI3K/AKT Pathway. Gland Surgery, 11(9): 1518–1528.

Li H, Zhao L, Lau YS, et al., 2021, Genome-Wide CRISPR Screen Identifies LGALS2 as an Oxidative Stress-Responsive Gene with an Inhibitory Function on Colon Tumor Growth. Oncogene, 40(1): 177–188.