Construction of prognostic risk markers for cervical cancer combined with anoikis-related genes and their clinical significance
Junmei Zhang A and Yanni Tian
A *
A
Abstract
Several studies have demonstrated that anoikis affects the development, metastasis and prognosis of cancer.
This study aimed to identify anoikis-related marker genes in cervical cancer (CC).
Least absolute shrinkage and selection operator (LASSO) combined with Cox regression analysis was used to construct a prognostic model and analyse the independent prognostic ability of riskscore. Receiver operating characteristic curve (ROC) and survival curves were used to evaluate and verify the performance and accuracy of the model. The nomogram of CC prognostic model was drawn using riskscore combined with clinical information. We analysed the relationship between prognostic riskscore and immune infiltration level and analysed immunophenoscore. Finally, qRT-PCR assay was used to verify the feature genes.
By Cox analysis, we found that the prognostic risk model could effectively predict the risk of CC in patients independently of other clinical factors. Both the levels of immune infiltration and the immunophenoscore were significantly lower in high-risk CC patients than those in low-risk patients, revealing that high-risk patients were likely to have bad response to immunotherapy. The qRT-PCR results of the feature genes were consistent with the results of gene expression in the database.
The prognostic model constructed, based on anoikis-related genes in CC, could predict the prognosis of CC patients.
The model described here can provide effective support for assessing prognostic risk and devising personalised protocols during clinical treatment.
Keywords: anoikis, cervical cancer, drug prediction, immune infiltration, immunotherapy, prognostic risk markers, single-cell, TMB.
References
Ashkenazi A, Fairbrother WJ, Leverson JD, Souers AJ (2017) From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors. Nature Reviews Drug Discovery 16, 273-284.
| Crossref | Google Scholar | PubMed |
Bedell SL, Goldstein LS, Goldstein AR, Goldstein AT (2020) Cervical cancer screening: past, present, and future. Sexual Medicine Reviews 8, 28-37.
| Crossref | Google Scholar | PubMed |
Blanche P, Dartigues J-F, Jacqmin-Gadda H (2013) Estimating and comparing time-dependent areas under receiver operating characteristic curves for censored event times with competing risks. Statistics in Medicine 32, 5381-5397.
| Crossref | Google Scholar | PubMed |
Buchheit CL, Angarola BL, Steiner A, Weigel KJ, Schafer ZT (2015) Anoikis evasion in inflammatory breast cancer cells is mediated by Bim-EL sequestration. Cell Death & Differentiation 22, 1275-1286.
| Crossref | Google Scholar | PubMed |
Buskwofie A, David-West G, Clare CA (2020) A review of cervical cancer: incidence and disparities. Journal of the National Medical Association 112, 229-232.
| Crossref | Google Scholar | PubMed |
Cai Z, Zhou F (2022) A novel Anoikis and immune-related genes marked prognostic signature for colorectal cancer. Medicine 101, e31127.
| Crossref | Google Scholar | PubMed |
Cao Z, Livas T, Kyprianou N (2016) Anoikis and EMT: lethal “liaisons” during cancer progression. Critical Reviews™ in Oncogenesis 21, 155-168.
| Crossref | Google Scholar | PubMed |
Chen S, Gu J, Zhang Q, Hu Y, Ge Y (2021) Development of biomarker signatures associated with anoikis to predict prognosis in endometrial carcinoma patients. Journal of Oncology 2021, 3375297.
| Crossref | Google Scholar | PubMed |
Crosbie EJ, Einstein MH, Franceschi S, Kitchener HC (2013) Human papillomavirus and cervical cancer. The Lancet 382, 889-899.
| Crossref | Google Scholar | PubMed |
Dasgupta S, Chakraborty SB, Roy A, Roychowdhury S, Panda CK (2003) Differential deletions of chromosome 3p are associated with the development of uterine cervical carcinoma in Indian patients. Molecular Pathology 56, 263-269.
| Crossref | Google Scholar | PubMed |
Dong Y, Ma W-M, Shi Z-D, et al. (2021) Role of NRP1 in bladder cancer pathogenesis and progression. Frontiers in Oncology 11, 685980.
| Crossref | Google Scholar | PubMed |
Ferrall L, Lin KY, Roden RBS, Hung C-F, Wu T-C (2021) Cervical cancer immunotherapy: facts and hopes. Clinical Cancer Research 27, 4953-4973.
| Crossref | Google Scholar | PubMed |
Fridman WH, Petitprez F, Meylan M, et al. (2021) B cells and cancer: to B or not to B? Journal of Experimental Medicine 218, e20200851.
| Crossref | Google Scholar |
Friedman J, Hastie T, Tibshirani R (2010) Regularization paths for generalized linear models via coordinate descent. Journal of Statistical Software 33, 1-22.
| Crossref | Google Scholar | PubMed |
Frisch SM, Ruoslahti E (1997) Integrins and anoikis. Current Opinion in Cell Biology 9, 701-706.
| Crossref | Google Scholar | PubMed |
Gaffney DK, Hashibe M, Kepka D, Maurer KA, Werner TL (2018) Too many women are dying from cervix cancer: problems and solutions. Gynecologic Oncology 151, 547-554.
| Crossref | Google Scholar | PubMed |
Hanzelmann S, Castelo R, Guinney J (2013) GSVA: gene set variation analysis for microarray and RNA-Seq data. BMC Bioinformatics 14, 7.
| Crossref | Google Scholar | PubMed |
Huang C, Liu Z, Xiao L, et al. (2019) Clinical significance of serum CA125, CA19-9, CA72-4, and fibrinogen-to-lymphocyte ratio in gastric cancer with peritoneal dissemination. Frontiers in Oncology 9, 1159.
| Crossref | Google Scholar | PubMed |
Ivanova M, Shivarov V (2021) HLA genotyping meets response to immune checkpoint inhibitors prediction: a story just started. International Journal of Immunogenetics 48, 193-200.
| Crossref | Google Scholar | PubMed |
Ji H, Li K, Jiang W, et al. (2021) MRVI1 and NTRK3 are potential tumor suppressor genes commonly inactivated by DNA methylation in cervical cancer. Frontiers in Oncology 11, 802068.
| Crossref | Google Scholar | PubMed |
Jin L, Chun J, Pan C, et al. (2018) The PLAG1-GDH1 axis promotes anoikis resistance and tumor metastasis through CamKK2-AMPK signaling in LKB1-deficient lung cancer. Molecular Cell 69, 87-99.e7 e87.
| Crossref | Google Scholar | PubMed |
Kahn JA (2009) HPV vaccination for the prevention of cervical intraepithelial neoplasia. New England Journal of Medicine 361, 271-278.
| Crossref | Google Scholar | PubMed |
Li Y, Yang S, Sadaoui NC, et al. (2020) Sustained adrenergic activation of YAP1 induces anoikis resistance in cervical cancer cells. iScience 23, 101289.
| Crossref | Google Scholar | PubMed |
Majidpoor J, Mortezaee K (2021) Steps in metastasis: an updated review. Medical Oncology 38, 3.
| Crossref | Google Scholar | PubMed |
Mauricio D, Zeybek B, Tymon-Rosario J, Harold J, Santin AD (2021) Immunotherapy in cervical cancer. Current Oncology Reports 23, 61.
| Crossref | Google Scholar | PubMed |
McAulay KA, Jarrett RF (2015) Human leukocyte antigens and genetic susceptibility to lymphoma. Tissue Antigens 86, 98-113.
| Crossref | Google Scholar | PubMed |
Mitra T, Elangovan S (2021) Cervical cancer development, chemoresistance, and therapy: a snapshot of involvement of microRNA. Molecular and Cellular Biochemistry 476, 4363-4385.
| Crossref | Google Scholar | PubMed |
Naranbhai V, Viard M, Dean M, et al. (2022) HLA-A*03 and response to immune checkpoint blockade in cancer: an epidemiological biomarker study. The Lancet Oncology 23, 172-184.
| Crossref | Google Scholar | PubMed |
Olusola P, Banerjee HN, Philley JV, Dasgupta S (2019) Human papilloma virus-associated cervical cancer and health disparities. Cells 8, 622.
| Crossref | Google Scholar |
Paoli P, Giannoni E, Chiarugi P (2013) Anoikis molecular pathways and its role in cancer progression. Biochimica et Biophysica Acta (BBA) – Molecular Cell Research 1833, 3481-3498.
| Crossref | Google Scholar | PubMed |
Patankar M, Mattila T, Väyrynen JP, et al. (2020) Putative anoikis-resistant subpopulations in colorectal carcinoma: a marker of adverse prognosis. APMIS 128, 390-400.
| Crossref | Google Scholar | PubMed |
Robinson MD, McCarthy DJ, Smyth GK (2010) edgeR: a bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139-140.
| Crossref | Google Scholar | PubMed |
Sakamoto S, Kyprianou N (2010) Targeting anoikis resistance in prostate cancer metastasis. Molecular Aspects of Medicine 31, 205-214.
| Crossref | Google Scholar | PubMed |
Schaafsma E, Fugle CM, Wang X, Cheng C (2021) Pan-cancer association of HLA gene expression with cancer prognosis and immunotherapy efficacy. British Journal of Cancer 125, 422-432.
| Crossref | Google Scholar | PubMed |
Schiffman M, Solomon D (2013) Cervical-cancer screening with human papillomavirus and cytologic cotesting. New England Journal of Medicine 369, 2324-2331.
| Crossref | Google Scholar | PubMed |
Sung H, Ferlay J, Siegel RL, et al. (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians 71, 209-249.
| Crossref | Google Scholar | PubMed |
Therneau TM (2022) A package for survival analysis in R. Available at https://cran.r-project.org/web/packages/survival/index.html
Tsu V, Jeronimo J (2016) Saving the world’s women from cervical cancer. New England Journal of Medicine 374, 2509-2511.
| Crossref | Google Scholar | PubMed |
Wilailak S, Kengsakul M, Kehoe S (2021) Worldwide initiatives to eliminate cervical cancer. International Journal of Gynecology & Obstetrics 155, 102-106.
| Crossref | Google Scholar | PubMed |
Xiao T, Li W, Wang X, et al. (2018) Estrogen-regulated feedback loop limits the efficacy of estrogen receptor-targeted breast cancer therapy. Proceedings of the National Academy of Sciences of the United States of America 115, 7869-7878.
| Crossref | Google Scholar | PubMed |
Ye G, Yang Q, Lei X, et al. (2020) Nuclear MYH9-induced CTNNB1 transcription, targeted by staurosporin, promotes gastric cancer cell anoikis resistance and metastasis. Theranostics 10, 7545-7560.
| Crossref | Google Scholar | PubMed |
Yesantharao P, Wang W, Ioannidis NM, et al. (2017) Cutaneous squamous cell cancer (cSCC) risk and the human leukocyte antigen (HLA) system. Human Immunology 78, 327-335.
| Crossref | Google Scholar | PubMed |
Yoshihara K, Shahmoradgoli M, Martínez E, et al. (2013) Inferring tumour purity and stromal and immune cell admixture from expression data. Nature Communications 4, 2612.
| Crossref | Google Scholar | PubMed |
Yu G, Wang L-G, Han Y, He Q-Y (2012) clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS: A Journal of Integrative Biology 16, 284-287.
| Crossref | Google Scholar | PubMed |
Yuan Y, Ye HQ, Ren QC (2018) Proliferative role of BDNF/TrkB signaling is associated with anoikis resistance in cervical cancer. Oncology Reports 40, 621-634.
| Crossref | Google Scholar | PubMed |
