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Original Research

Open Access

Tumour mutational burden and immune-cell infiltration in cervical squamous cell carcinoma

  • Shanquan Yan1
  • Dan Liu1
  • Xitong Yang2
  • Guangming Wang2,*,

1School of Clinical Medicine, Dali University, 671000 Dali, Yunnan, China

2Genetic Testing Center, The First Afliated Hospital of Dali University, 671000 Dali, Yunnan, China

DOI: 10.22514/ejgo.2022.016 Vol.43,Issue 3,June 2022 pp.118-126

Submitted: 15 March 2022 Accepted: 24 April 2022

Published: 15 June 2022

*Corresponding Author(s): Guangming Wang E-mail: wgm1991@dali.edu.cn

Abstract

Background: Cervical carcinoma is one of the most common gynaecological malignancies worldwide and severely affects the health of women; cervical squamous cell carcinoma is the most prevalent form. The aim of this study was to assess the tumour mutational burden (TMB) and immune infiltration in cervical squamous cell carcinoma. Methods: Cervical carcinoma-related data were downloaded from The Cancer Genome Atlas (TCGA). The patients were divided into low- and high- TMB groups based on the median TMB score. Differentially expressed genes (DEGs) were identified based on the TMB score. Bioinformatics tools were used to analyse the immune infiltration in cervical squamous cell carcinoma and patient survival. Results: Single nucleotide polymorphisms were more familiar than deletions or insertions, and C>T was the primary single nucleotide variant. Moreover, TTN, PIK3CA, and MUC16 were the three main genes with mutations. The survival curve was not clinically significant, but a correlation was observed between high TMB levels and tumour grade. 69 DEGs were identified, which primarily consisted of the FC receptor, Ras, and MAPK signalling pathways. Furthermore, a significant difference was observed in the extent of infiltration of CD4+ T cells, regulatory T cells, and natural killer cells. Conclusions: We observed a relationship between high TMB standards and the development of cervical squamous cell carcinoma. However, we could not present an immune prognostic model for cervical squamous cell carcinoma.


Keywords

tumour mutational burden; cervical squamous cell carcinoma; immune infiltration; bioinformatics


Cite and Share

Shanquan Yan,Dan Liu,Xitong Yang,Guangming Wang. Tumour mutational burden and immune-cell infiltration in cervical squamous cell carcinoma. European Journal of Gynaecological Oncology. 2022. 43(3);118-126.

References

[1] Lijuan Li, Youzhen Luo. Research progress on the etiology and prevention of cervical cancer, Modern Medicine and Health Research. 2019; 3: 16–19

[2] Yu Wang, Shufang Song, Feng Liu. Research progress on the epidemiological characteristics and high-risk factors of cervical cancer in China. Maternal & Child Health Care of China. 2019; 34: 1206–1208.

[3] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians. 2021; 71: 209–249.

[4] Hancock G, Hellner K, Dorrell L. Therapeutic HPV vaccines. Best Practice & Research Clinical Obstetrics & Gynaecology. 2018; 47: 59–72.

[5] Xiaohui Wang. The prevalence of cervical cancer and its prevention and control strategies. Gansu Medical Journal. 2020; 39: 1064–1066,1076.

[6] TWu NF, Ou YC, Liao CI, Chang WY, Yang LY, Tang YH, et al. Prognostic factor and adjuvant therapy on survival in early-stage cervical adenocarcinoma /adenosquamous carcinoma after primary radical surgery: a Taiwanese Gynecologic Oncology Group (TGOG) study. Surgical Oncology. 2016; 25: 229–235.

[7] Fumet J, Truntzer C, Yarchoan M, Ghiringhelli F. Tumour mutational burden as a biomarker for immunotherapy: Current data and emerging concepts. European Journal of Cancer. 2020; 131: 40–50.

[8] Miller A, Asmann Y, Cattaneo L, Braggio E, Keats J, Auclair D, et al. High somatic mutation and neoantigen burden are correlated with decreased progression-free survival in multiple myeloma. Blood Cancer Journal. 2017; 7: e612–e612.

[9] Jiang F, Wu C, Wang M, Wei K, Zhou G, Wang J. Multi-omics analysis of tumor mutation burden combined with immune infiltrates in melanoma. Clinica Chimica Acta. 2020; 511: 306–318.

[10] Zhao L, Fu X, Han X, Yu Y, Ye Y, Gao J. Tumor mutation burden in connection with immune-related survival in uterine corpus endometrial carcinoma. Cancer Cell International. 2021. 21: 80

[11] Napoletano C, Rughetti A, Landi R, Pinto D, Bellati F, Rahimi H, et al. Immunogenicity of Allo-Vesicle Carrying ERBB2 Tumor Antigen for Dendritic Cell-Based Anti-Tumor Immunotherapy. International Journal of Immunopathology and Pharmacology. 2009; 22: 647–658.

[12] Dionisi M, De Archangelis C, Battisti F, Rahimi Koshkaki H, Belleudi F, Zizzari IG, et al. Tumor-Derived Microvesicles Enhance Cross-Processing Ability of Clinical Grade Dendritic Cells. Frontiers in Immunology. 2018; 9: 2481.

[13] Genetic Tumor Markers Collaboration Group, Tumor Biomarker Committee, China Anti-cancer Association, Molecular Pathology Col-laboration Group, Tumor Pathology Committee, China Anti-Cancer Association. Chinese Expert Consensus on Tumor Mutation Burden Detection and Clinical Application (2020 Edition). Chinese Journal of Oncology Prevention and Treatment. 2020; 12: 485–494.

[14] Mayakonda A, Lin D, Assenov Y, Plass C, Koeffler HP. Maftools: efficient and comprehensive analysis of somatic variants in cancer. Genome Research. 2018; 28: 1747–1756.

[15] Büttner R, Longshore JW, López-Ríos F, Merkelbach-Bruse S, Normanno N, Rouleau E, et al. Implementing TMB measurement in clinical practice: considerations on assay requirements. ESMO Open. 2019; 4: e000442.

[16] Chen B, Khodadoust MS, Liu CL, Newman AM, Alizadeh AA. Profiling Tumor Infiltrating Immune Cells with CIBERSORT. Methods in Molecular Biology. 2018; 12: 243–259.

[17] Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, et al. Robust enumeration of cell subsets from tissue expression profiles. Nature Methods. 2015; 12: 453–457.

[18] Ping Liu. Big Data Evaluation of Cervical Cancer Clinical Epidemiology in Mainland China for 13 Years. Chinese Journal of Practical Gynecology and Obstetrics. 2018; 34: 41–45.

[19] Mosele F, Remon J, Mateo J, Westphalen CB, Barlesi F, Lolkema MP, et al. Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group. Annals of Oncology. 2020; 31: 1491–1505.

[20] Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nature Immunology. 2002; 3: 991–998.

[21] Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015; 348: 69–74.

[22] Janjigian YY, Wolchok JD, Ariyan CE. Eradicating micrometastases with immune checkpoint blockade: Strike while the iron is hot. Cancer Cell. 2021; 39: 738–742.

[23] Yao J, Xi W, Zhu Y, Wang H, Hu X, Guo J. Checkpoint molecule PD-1-assisted CD8 + T lymphocyte count in tumor microenvironment predicts overall survival of patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors. Cancer Management and Research. 2018; 10: 3419–3431.

[24] Wang Q, Lou W, Di W, Wu X. Prognostic value of tumor PD-L1 expression combined with CD8 + tumor infiltrating lymphocytes in high grade serous ovarian cancer. International Immunopharmacology. 2017; 52: 7–14.

[25] Withers SS, Skorupski KA, York D, Choi JW, Woolard KD, Laufer-Amorim R, et al. Association of macrophage and lymphocyte infiltration with outcome in canine osteosarcoma. Veterinary and Comparative Oncology. 2019; 17: 49–60.

[26] Buddingh EP, Kuijjer ML, Duim RAJ, Bürger H, Agelopoulos K, Myklebost O, et al. Tumor-Infiltrating Macrophages are Associated with Metastasis Suppression in High-Grade Osteosarcoma: a Rationale for Treatment with Macrophage Activating Agents. Clinical Cancer Research. 2011; 17: 2110–2119.

[27] Ali HR, Provenzano E, Dawson S-, Blows FM, Liu B, Shah M, et al. Association between CD8+ T-cell infiltration and breast cancer survival in 12 439 patients. Annals of Oncology. 2014; 25: 1536–1543.

[28] Kalathil SG, Hutson A, Barbi J, Iyer R, Thanavala Y. Augmentation of IFN-γ+ CD8+ T cell responses correlates with survival of HCC patients on sorafenib therapy. JCI Insight. 2019; 4: e130116.

[29] Ogura A, Akiyoshi T, Yamamoto N, Kawachi H, Ishikawa Y, Mori S, et al. Pattern of programmed cell death-ligand 1 expression and CD8-positive T-cell infiltration before and after chemoradiotherapy in rectal cancer. European Journal of Cancer. 2018; 91: 11–20.


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