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Current Gene Therapy

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ISSN (Print): 1566-5232
ISSN (Online): 1875-5631

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Research Article

ZNF695, A Potential Prognostic Biomarker, Correlates with Im mune Infiltrates in Cervical Squamous Cell Carcinoma and Endoce rvical Adenocarcinoma: Bioinformatic Analysis and Experimental Verification

Author(s): Xiaojuan Ding, Ailing Wan, Xin Qi, Ke'er Jiang, Zhao Liu and Buze Chen*

Volume 24, Issue 5, 2024

Published on: 01 March, 2024

Page: [441 - 452] Pages: 12

DOI: 10.2174/0115665232285216240228071244

Price: $65

Abstract

Background: The role of Zinc Finger Protein 695 (ZNF695) is unclear in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC).

Objective: The objective of this study was to conduct a comprehensive analysis and experimental validation of ZNF695 in CESC.

Methods: The study investigated the expression of ZNF695 in both pan-cancer and CESC, utilizing data from The Cancer Genome Atlas (TCGA) database to assess its diagnostic value. The present study investigated the association between ZNF695 expression levels and clinical characteristics, as well as prognosis, in patients with CESC. The study explored potential regulatory networks involving ZNF695, including its association with immune infiltration, immune score, stemness index based on mRNA expression (mRNAsi), and drug sensitivity in CESC. We explored the expression of ZNF695 in CESC single cells. ZNF695 expression was validated using GSE29570.

Results: ZNF695 was found to be aberrantly expressed in pan-cancer and CESC. There was a significant correlation observed between an elevated level of ZNF695 expression in patients with CESC and histological grade (p = 0.017). Furthermore, a strong association was found between high ZNF695 expression in CESC patients and poorer overall survival (OS) (HR: 1.87; 95% CI: 1.17-3.00; p = 0.009), Progression-free Survival (PFS) (HR: 1.86; 95% CI: 1.16-2.98; p = 0.010), and Disease-specific Survival (DSS) (HR: 1.98; 95% CI: 1.15-3.42; p = 0.014). The expression of ZNF695 in CESC patients (p = 0.006) was identified as an independent prognostic determinant. ZNF695 was associated with steroid hormone biosynthesis, oxidative phosphorylation, and so on. ZNF695 expression correlated with immune infiltration, immune score, and mRNAsi in CESC. ZNF695 expression significantly and negatively correlated with AICA ribonucleotide, BIX02189, QL-XI-92, STF-62247, and SNX-2112 in CESC. ZNF695 gene was upregulated in CESC tissues and cell lines. ZNF695 was significantly upregulated in the CESC cell lines.

Conclusion: ZNF695 may be a potential prognostic biomarker and immunotherapeutic target for CESC patients.

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[1]
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[2]
Cohen PA, Jhingran A, Oaknin A, Denny L. Cervical cancer. Lancet 2019; 393(10167): 169-82.
[http://dx.doi.org/10.1016/S0140-6736(18)32470-X] [PMID: 30638582]
[3]
Arbyn M, Weiderpass E, Bruni L, et al. Estimates of incidence and mortality of cervical cancer in 2018: A worldwide analysis. Lancet Glob Health 2020; 8(2): e191-203.
[http://dx.doi.org/10.1016/S2214-109X(19)30482-6] [PMID: 31812369]
[4]
Zhou S, Wang X, Ding J, Yang H, Xie Y. Increased ATG5 expression predicts poor prognosis and promotes emt in cervical carcinoma. Front Cell Dev Biol 2021; 9: 757184.
[http://dx.doi.org/10.3389/fcell.2021.757184] [PMID: 34901004]
[5]
Small W Jr, Bacon MA, Bajaj A, et al. Cervical cancer: A global health crisis. Cancer 2017; 123(13): 2404-12.
[http://dx.doi.org/10.1002/cncr.30667] [PMID: 28464289]
[6]
Marchetti C, Fagotti A, Tombolini V, Scambia G, De Felice F. Survival and toxicity in neoadjuvant chemotherapy plus surgery versus definitive chemoradiotherapy for cervical cancer: A systematic review and meta-analysis. Cancer Treat Rev 2020; 83: 101945.
[http://dx.doi.org/10.1016/j.ctrv.2019.101945] [PMID: 31838220]
[7]
Zhao YC, Wang TJ, Qu GH, et al. TPM3: A novel prognostic biomarker of cervical cancer that correlates with immune infiltration and promotes malignant behavior in vivo and in vitro. Am J Cancer Res 2023; 13(7): 3123-39.
[PMID: 37559998]
[8]
Juárez-Méndez S, Zentella-Dehesa A, Villegas-Ruíz V, et al. Splice variants of zinc finger protein 695 mRNA associated to ovarian cancer. J Ovarian Res 2013; 6(1): 61.
[http://dx.doi.org/10.1186/1757-2215-6-61] [PMID: 24007497]
[9]
Li C, Kuang L, Zhu B, Chen J, Wang X, Huang X. Identification of prognostic risk factors of acute lymphoblastic leukemia based on mRNA expression profiling. Neoplasma 2017; 64(4): 494-501.
[http://dx.doi.org/10.4149/neo_2017_402] [PMID: 28485154]
[10]
Rosa R, Villegas-Ruíz V, Caballero-Palacios MC, et al. Expression of ZNF695 transcript variants in childhood B-Cell acute lymphoblastic leukemia. Genes 2019; 10(9): 716.
[http://dx.doi.org/10.3390/genes10090716] [PMID: 31527520]
[11]
Ke ZB, You Q, Chen JY, et al. A radiation resistance related index for biochemical recurrence and tumor immune environment in prostate cancer patients. Comput Biol Med 2022; 146: 105711.
[http://dx.doi.org/10.1016/j.compbiomed.2022.105711] [PMID: 35701253]
[12]
Xu H, Wang H, Li G, Jin X, Chen B. The immune-related gene ELF3 is a novel biomarker for the prognosis of ovarian cancer. Int J Gen Med 2021; 14: 5537-48.
[http://dx.doi.org/10.2147/IJGM.S332320] [PMID: 34531679]
[13]
Dong Y, Jin F, Wang J, et al. SFXN3 is associated with poor clinical outcomes and sensitivity to the hypomethylating therapy in non-M3 acute myeloid leukemia patients. Curr Gene Ther 2023; 23(5): 410-8.
[http://dx.doi.org/10.2174/1566523223666230724121515] [PMID: 37491851]
[14]
Yang D, Liu M, Jiang J, et al. Comprehensive analysis of DMRT3 as a potential biomarker associated with the immune infiltration in a pan-cancer analysis and validation in lung adenocarcinoma. Cancers 2022; 14(24): 6220.
[http://dx.doi.org/10.3390/cancers14246220] [PMID: 36551704]
[15]
Chen J, Tang H, Li T, et al. Comprehensive analysis of the expression, prognosis, and biological significance of OVOLs in breast cancer. Int J Gen Med 2021; 14: 3951-60.
[http://dx.doi.org/10.2147/IJGM.S326402] [PMID: 34345183]
[16]
Lin Z, Huang W, Yi Y, et al. LncRNA ADAMTS9-AS2 is a prognostic biomarker and correlated with immune infiltrates in lung adenocarcinoma. Int J Gen Med 2021; 14: 8541-55.
[http://dx.doi.org/10.2147/IJGM.S340683] [PMID: 34849000]
[17]
Yi W, Shen H, Sun D, et al. Low expression of long noncoding RNA SLC26A4 antisense RNA 1 Is an independent prognostic biomarker and correlate of immune infiltrates in breast cancer. Med Sci Monit 2021; 27: e934522.
[PMID: 34880202]
[18]
Liang W, Lu Y, Pan X, et al. Decreased expression of a novel lncRNA FAM181A-AS1 is associated with poor prognosis and immune infiltration in lung adenocarcinoma. Pharm Genomics Pers Med 2022; 15: 985-98.
[http://dx.doi.org/10.2147/PGPM.S384901] [PMID: 36482943]
[19]
Han Q, Cui Z, Wang Q, Pang F, Li D, Wang D. Upregulation of OTX2-AS1 is associated with immune infiltration and predicts prognosis of gastric cancer. Technol Cancer Res Treat 2023; 22
[http://dx.doi.org/10.1177/15330338231154091] [PMID: 36740995]
[20]
Chen T, Zhu C, Wang X, Pan Y. LncRNA ELF3-AS1 is a prognostic biomarker and correlated with immune infiltrates in hepatocellular carcinoma. Can J Gastroenterol Hepatol 2021; 2021: 1-12.
[http://dx.doi.org/10.1155/2021/8323487] [PMID: 34336727]
[21]
Wang L, Yu Q, Chen X, et al. Identification of HnRNP family as prognostic biomarkers in five major types of gastrointestinal cancer. Curr Gene Ther 2022; 22(5): 449-61.
[http://dx.doi.org/10.2174/1566523222666220613113647] [PMID: 35794744]
[22]
Liu J, Lichtenberg T, Hoadley KA, et al. An integrated TCGA pan-cancer clinical data resource to drive high-quality survival outcome analytics. Cell 2018; 173(2): 400-416.e11.
[http://dx.doi.org/10.1016/j.cell.2018.02.052] [PMID: 29625055]
[23]
Lu X, Jing L, Liu S, Wang H, Chen B. miR-149-3p Is a potential prognosis biomarker and correlated with immune infiltrates in uterine corpus endometrial carcinoma. Int J Endocrinol 2022; 2022: 1-15.
[http://dx.doi.org/10.1155/2022/5006123] [PMID: 35719192]
[24]
Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 2014; 15(12): 550.
[http://dx.doi.org/10.1186/s13059-014-0550-8] [PMID: 25516281]
[25]
Yu G, Wang LG, Han Y, He QY. clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS 2012; 16(5): 284-7.
[http://dx.doi.org/10.1089/omi.2011.0118] [PMID: 22455463]
[26]
Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci 2005; 102(43): 15545-50.
[http://dx.doi.org/10.1073/pnas.0506580102] [PMID: 16199517]
[27]
Hänzelmann S, Castelo R, Guinney J. GSVA: Gene set variation analysis for microarray and RNA-Seq data. BMC Bioinformatics 2013; 14(1): 7.
[http://dx.doi.org/10.1186/1471-2105-14-7] [PMID: 23323831]
[28]
Bindea G, Mlecnik B, Tosolini M, et al. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity 2013; 39(4): 782-95.
[http://dx.doi.org/10.1016/j.immuni.2013.10.003] [PMID: 24138885]
[29]
Chen B, Lu X, Zhou Q, et al. PAXIP1-AS1 is associated with immune infiltration and predicts poor prognosis in ovarian cancer. PLoS One 2023; 18(8): e0290031.
[http://dx.doi.org/10.1371/journal.pone.0290031] [PMID: 37582104]
[30]
Yoshihara K, Shahmoradgoli M, Martínez E, et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun 2013; 4(1): 2612.
[http://dx.doi.org/10.1038/ncomms3612] [PMID: 24113773]
[31]
Bonneville R, Krook MA, Kautto EA, Miya J, Wing MR, Chen HZ, et al. Landscape of microsatellite instability across 39 cancer types. JCO precision oncology 2017; 2017
[32]
Zhong F, Liu J, Gao C, Chen T, Li B. Downstream regulatory network of MYBL2 mediating its oncogenic role in melanoma. Front Oncol 2022; 12: 816070.
[http://dx.doi.org/10.3389/fonc.2022.816070] [PMID: 35664780]
[33]
Lyu G, Li D, Xiong H, et al. Quantitative proteomic analyses idenify STO/BBX24 -related proteins induced by UV-B. Int J Mol Sci 2020; 21(7): 2496.
[http://dx.doi.org/10.3390/ijms21072496] [PMID: 32260266]
[34]
Becker LS, Al Smadi MA, Koch H, Abdul-Khaliq H, Meese E, Abu-Halima M. Towards a more comprehensive picture of the microRNA-23a/b-3p impact on impaired male fertility. Biology 2023; 12(6): 800.
[http://dx.doi.org/10.3390/biology12060800] [PMID: 37372085]
[35]
Chen H, Zhao X, Li Y, et al. High expression of TMEM33 predicts poor prognosis and promotes cell proliferation in cervical cancer. Front Genet 2022; 13: 908807.
[http://dx.doi.org/10.3389/fgene.2022.908807] [PMID: 35832191]
[36]
Xie Q, Ou-yang W, Zhang M, Wang H, Yue Q. Decreased expression of NUSAP1 predicts poor overall survival in cervical cancer. J Cancer 2020; 11(10): 2852-63.
[http://dx.doi.org/10.7150/jca.34640] [PMID: 32226503]
[37]
Shinden Y, Hirashima T, Nohata N, et al. Molecular pathogenesis of breast cancer: Impact of miR-99a-5p and miR-99a-3p regulation on oncogenic genes. J Hum Genet 2021; 66(5): 519-34.
[http://dx.doi.org/10.1038/s10038-020-00865-y] [PMID: 33177704]
[38]
Ding B, Sun W, Han S, Cai Y, Ren M, Shen Y. Cytochrome P450 1A1 gene polymorphisms and cervical cancer risk. Medicine 2018; 97(13): e0210.
[http://dx.doi.org/10.1097/MD.0000000000010210] [PMID: 29595663]
[39]
Alshammari FOFO, Al-saraireh YM, Youssef AMM, Al-Sarayra YM, Alrawashdeh HM. Cytochrome P450 1B1 overexpression in cervical cancers: Cross-sectional Study. Interact J Med Res 2021; 10(4): e31150.
[http://dx.doi.org/10.2196/31150] [PMID: 34636736]
[40]
Hofsjö A, Bohm-Starke N, Bergmark K, Masironi B, Sahlin L. Sex steroid hormone receptor expression in the vaginal wall in cervical cancer survivors after radiotherapy. Acta Oncol 2019; 58(8): 1107-15.
[http://dx.doi.org/10.1080/0284186X.2019.1598574] [PMID: 30957588]
[41]
Lin PY, Chang SN, Hsiao TH, Huang BT, Lin CH, Yang PC. Association between parkinson disease and risk of cancer in Taiwan. JAMA Oncol 2015; 1(5): 633-40.
[http://dx.doi.org/10.1001/jamaoncol.2015.1752] [PMID: 26181771]
[42]
Zhang X, Dai B, Zhang B, Wang Z. Vitamin A and risk of cervical cancer: A meta-analysis. Gynecol Oncol 2012; 124(2): 366-73.
[http://dx.doi.org/10.1016/j.ygyno.2011.10.012] [PMID: 22005522]
[43]
Jonsson M, Fjeldbo CS, Holm R, Stokke T, Kristensen GB, Lyng H. Mitochondrial function of CKS2 oncoprotein links oxidative phosphorylation with cell division in chemoradioresistant cervical cancer. Neoplasia 2019; 21(4): 353-62.
[http://dx.doi.org/10.1016/j.neo.2019.01.002] [PMID: 30856376]
[44]
Monk BJ, Enomoto T, Kast WM, et al. Integration of immunotherapy into treatment of cervical cancer: Recent data and ongoing trials. Cancer Treat Rev 2022; 106: 102385.
[http://dx.doi.org/10.1016/j.ctrv.2022.102385] [PMID: 35413489]
[45]
Turinetto M, Valsecchi AA, Tuninetti V, Scotto G, Borella F, Valabrega G. Immunotherapy for cervical cancer: Are we ready for prime time? Int J Mol Sci 2022; 23(7): 3559.
[http://dx.doi.org/10.3390/ijms23073559] [PMID: 35408919]
[46]
Di Fiore R, Suleiman S, Drago-Ferrante R, et al. Cancer stem cells and their possible implications in cervical cancer: A short review. Int J Mol Sci 2022; 23(9): 5167.
[http://dx.doi.org/10.3390/ijms23095167] [PMID: 35563557]
[47]
Wang L, Liu W, Liu J, et al. Identification of immune-related therapeutically relevant biomarkers in breast cancer and breast cancer stem cells by transcriptome-wide analysis: A clinical prospective study. Front Oncol 2021; 10: 554138.
[http://dx.doi.org/10.3389/fonc.2020.554138] [PMID: 33718103]

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