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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2022

Open Access 01-12-2022 | Cervical Cancer | Research

Identification of COPA as a potential prognostic biomarker and pharmacological intervention target of cervical cancer by quantitative proteomics and experimental verification

Authors: Huiqiong Bao, Xiaobin Li, Zhixing Cao, Zhihong Huang, Li Chen, Mingbing Wang, Jiali Hu, Wenting Li, Hongwei Sun, Xue Jiang, Ping Mei, Huawen Li, Ligong Lu, Meixiao Zhan

Published in: Journal of Translational Medicine | Issue 1/2022

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Abstract

Background

Cervical cancer is the most fatal gynecological carcinoma in the world. It is urgent to explore novel prognostic biomarkers and intervention targets for cervical cancer.

Methods

Through integrated quantitative proteomic strategy, we investigated the protein expression profiles of cervical cancer; 28 fresh frozen tissue samples (11 adenocarcinoma (AC), 12 squamous cell carcinoma (SCC) and 5 normal cervixes (HC)) were included in discover cohort; 45 fresh frozen tissue samples (19 AC, 18 SCC and 8 HC) were included in verification cohort; 140 paraffin-embedded tissues samples of cervical cancer (85 AC and 55 SCC) were used for immunohistochemical evaluation (IHC) of coatomer protein subunit alpha (COPA) as a prognostic biomarker for cervical cancer; how deficiency of COPA affects cell viability and tumorigenic ability of cervical cancer cells (SiHa cells and HeLa cells) were evaluated by cell counting kit-8 and clone formation in vitro.

Results

We identified COPA is a potential prognostic biomarker for cervical cancer in quantitative proteomics analysis. By retrospective IHC analysis, we additionally verified the proteomics results and demonstrated moderate or strong IHC staining for COPA is an unfavourable independent prognostic factor for cervical cancer. We also identified COPA is a potential pharmacological intervention target of cervical cancer by a series of in vitro experiments.

Conclusion

This study is the first to demonstrate that COPA may contribute to progression of cervical cancer. It can serve as a potential prognostic biomarker and promising intervention target for cervical cancer.
Appendix
Available only for authorised users
Literature
1.
Ahmad A, Ansari IA. A Comprehensive Review on Crosstalk of Human Papilloma Virus oncoproteins and developmental/self-renewal pathways during the pathogenesis of uterine cervical cancer. Curr Mol Med. 2020;89:234.
2.
Cohen JD, Li L, Wang Y, Thoburn C, Afsari B, Danilova L, Douville C, Javed AA, Wong F, Mattox A. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science. 2018;359:926–30.CrossRefPubMedPubMedCentral
3.
Lu X, Wang Z, Zhang S, Konijnenberg AP, Ouyang Y, Zhao C, Cai Y. Microscopic phase reconstruction of cervical exfoliated cell under partially coherent illumination. J Biophotonics. 2021;14:e202000401.PubMed
4.
Zorzi M, Mistro A, Farruggio A, Bartolomeis L, Frayle-Salamanca H, Baboci L, Bertazzo A, Cocco P, Fedato C, Gennaro M, et al. Use of a high-risk human papillomavirus DNA test as the primary test in a cervical cancer screening programme: a population-based cohort study. BJOG. 2013;120:1260–7.CrossRefPubMed
5.
Han R, Shi Q, Wu S, Yin D, Peng M, Dong D, Zheng Y, Guo Y, Zhang R, Hu F. Dissemination of Carbapenemases (KPC, NDM, OXA-48, IMP, and VIM) Among Carbapenem-Resistant Enterobacteriaceae Isolated From Adult and Children Patients in China. Front Cell Infect Microbiol. 2020;10:314.CrossRefPubMedPubMedCentral
6.
Islami F, Fedewa SA, Jemal A. Trends in cervical cancer incidence rates by age, race/ethnicity, histological subtype, and stage at diagnosis in the United States. Prev Med. 2019;123:316–23.CrossRefPubMed
7.
Wu C, Zhu X, Kang Y, Cao Y, Lu P, Zhou W, Zhou H, Zhang Y, Song Y. Epidemiology of Humanpapilloma virus infection among women in Fujian China. BMC Public Health. 2017;18:95.CrossRefPubMedPubMedCentral
8.
Zhou J, Wu SG, Sun JY, Li FY, Lin HX, Chen QH, He ZY. Comparison of clinical outcomes of squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma of the uterine cervix after definitive radiotherapy: a population-based analysis. J Cancer Res Clin Oncol. 2017;143:115–22.CrossRefPubMed
9.
Sun X, Wan JJ, Qian K. Designed microdevices for in vitro diagnostics. Small Methods. 2017;1:1700196.CrossRef
10.
Cao J, Shi X, Gurav DD, Huang L, Su H, Li K, Niu J, Zhang M, Wang Q, Jiang M. Metabolic fingerprinting on synthetic alloys for medulloblastoma diagnosis and radiotherapy evaluation. Adv Mater. 2020;32:2000906.CrossRef
11.
Su H, Li X, Huang L, Cao J, Zhang M, Vedarethinam V, Di W, Hu Z, Qian K. Plasmonic alloys reveal a distinct metabolic phenotype of early gastric cancer. Adv Mater. 2021;33:2007978.CrossRef
12.
Pappa KI, Christou P, Xholi A, Mermelekas G, Kontostathi G, Lygirou V, Makridakis M, Zoidakis J, Anagnou NP. Membrane proteomics of cervical cancer cell lines reveal insights on the process of cervical carcinogenesis. Int J Oncol. 2018;53:2111–22.PubMed
13.
Zhang L, Jin J, Zhang L, Hu R, Gao L, Huo X, Liu D, Ma X, Wang C, Han J, et al. Quantitative analysis of differential protein expression in cervical carcinoma cells after zeylenone treatment by stable isotope labeling with amino acids in cell culture. J Proteomics. 2015;126:279–87.CrossRefPubMed
14.
Xu T, Pang Q, Zhou D, Zhang A, Luo S, Wang Y, Yan X. Proteomic investigation into betulinic acid-induced apoptosis of human cervical cancer HeLa cells. PLoS ONE. 2014;9:e105768.CrossRefPubMedPubMedCentral
15.
Choi YP, Kang S, Hong S, Xie X, Cho NH. Proteomic analysis of progressive factors in uterine cervical cancer. Proteomics. 2005;5:1481–93.CrossRefPubMed
16.
Arakel EC, Schwappach B. Formation of COPI-coated vesicles at a glance. J Cell Sci. 2018;131:89.
17.
Song Y, An O, Ren X, Chan THM, Tay DJT, Tang SJ, Han J, Hong H, Ng VHE, Ke X, et al. RNA editing mediates the functional switch of COPA in a novel mechanism of hepatocarcinogenesis. J Hepatol. 2021;74:135–47.CrossRefPubMed
18.
19.
Zhou Q, Andersson R, Hu D, Bauden M, Kristl T, Sasor A, Pawłowski K, Pla I, Hilmersson KS, Zhou M, et al. Quantitative proteomics identifies brain acid soluble protein 1 (BASP1) as a prognostic biomarker candidate in pancreatic cancer tissue. EBioMedicine. 2019;43:282–94.CrossRefPubMedPubMedCentral
20.
Bao H, Sin TK, Zhang G. Activin A induces tumorigenesis of leiomyoma via regulation of p38β MAPK-mediated signal cascade. Biochem Biophys Res Commun. 2020;529:379–85.CrossRefPubMed
21.
Peng X, Xu X, Wang Y, Hawke DH, Yu S, Han L, Zhou Z, Mojumdar K, Jeong KJ, Labrie M. A-to-I RNA editing contributes to proteomic diversity in cancer. Cancer Cell. 2018;33:817–28.CrossRefPubMedPubMedCentral
22.
Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47:D607-d613.PubMed
23.
Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13:2498–504.PubMedPubMedCentral
24.
Tang Z, Kang B, Li C, Chen T, Zhang Z. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019;47:W556-w560.CrossRefPubMedPubMedCentral
25.
Sobsey CA, Ibrahim S, Richard VR, Gaspar V, Mitsa G, Lacasse V, Zahedi RP, Batist G, Borchers CH. Targeted and untargeted proteomics approaches in biomarker development. Proteomics. 2020;20:1900029.CrossRef
26.
27.
Gallien S, Duriez E, Crone C, Kellmann M, Moehring T, Domon B. Targeted proteomic quantification on quadrupole-orbitrap mass spectrometer. Mol Cell Proteomics. 2012;11:1709–23.CrossRefPubMedPubMedCentral
28.
Kontostathi G, Zoidakis J, Anagnou NP, Pappa KI, Vlahou A, Makridakis M. Proteomics approaches in cervical cancer: focus on the discovery of biomarkers for diagnosis and drug treatment monitoring. Expert Rev Proteomics. 2016;13:731–45.CrossRefPubMed
29.
Zhao Q, He Y, Wang X-L, Zhang Y-X, Wu Y-M. Differentially expressed proteins among normal cervix, cervical intraepithelial neoplasia and cervical squamous cell carcinoma. Clin Transl Oncol. 2015;17:620–31.CrossRefPubMed
30.
Escobar-Hoyos LF, Yang J, Zhu J, Cavallo J-A, Zhai H, Burke S, Koller A, Chen EI, Shroyer KR. Keratin 17 in premalignant and malignant squamous lesions of the cervix: proteomic discovery and immunohistochemical validation as a diagnostic and prognostic biomarker. Mod Pathol. 2014;27:621–30.CrossRefPubMed
31.
Wang W, Jia H, Huang J, Liang Y, Tan H, Geng H, Guo L, Yao S. Identification of biomarkers for lymph node metastasis in early-stage cervical cancer by tissue-based proteomics. Br J Cancer. 2014;110:1748–58.CrossRefPubMedPubMedCentral
32.
Song JY, Bae HS, Koo DH, Lee JK, Jung HH, Lee KW, Lee NW. Candidates for tumor markers of cervical cancer discovered by proteomic analysis. J Korean Med Sci. 2012;27:1479–85.CrossRefPubMedPubMedCentral
33.
Fukushima C, Murakami A, Yoshitomi K, Sueoka K, Nawata S, Nakamura K, Sugino N. Comparative proteomic profiling in squamous cell carcinoma of the uterine cervix. Proteomics-Clin Appl. 2011;5:133–40.CrossRefPubMed
34.
Lomnytska MI, Becker S, Hellman K, Hellström AC, Souchelnytskyi S, Mints M, Hellman U, Andersson S, Auer G. Diagnostic protein marker patterns in squamous cervical cancer. Proteomics-Clin Appl. 2010;4:17–31.CrossRefPubMed
35.
Arnouk H, Merkley MA, Podolsky RH, Stöppler H, Santos C, Álvarez M, Mariategui J, Ferris D, Lee JR, Dynan WS. Characterization of molecular markers indicative of cervical cancer progression. Proteomics-Clinical Applications. 2009;3:516–27.CrossRefPubMedPubMedCentral
36.
Zhu X, Lv J, Yu L, Zhu X, Wu J, Zou S, Jiang S. Proteomic identification of differentially-expressed proteins in squamous cervical cancer. Gynecol Oncol. 2009;112:248–56.CrossRefPubMed
37.
Bae SM, Lee C-H, Cho YL, Nam KH, Kim YW, Kim CK, Han BD, Lee YJ, Chun HJ, Ahn WS. Two-dimensional gel analysis of protein expression profile in squamous cervical cancer patients. Gynecol Oncol. 2005;99:26–35.CrossRefPubMed
38.
Huang H, Feng YL, Wan T, Zhang YN, Cao XP, Huang YW, Xiong Y, Huang X, Zheng M, Li YF, et al. Effectiveness of sequential chemoradiation vs concurrent chemoradiation or radiation alone in adjuvant treatment after hysterectomy for cervical cancer: The STARS Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021;7:361–9.CrossRefPubMed
39.
Cibula D, Pötter R, Planchamp F, Avall-Lundqvist E, Fischerova D, Haie Meder C, Köhler C, Landoni F, Lax S, Lindegaard JC, et al. The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology guidelines for the management of patients with cervical cancer. Radiother Oncol. 2018;127:404–16.CrossRefPubMed
40.
Koh WJ, Abu-Rustum NR, Bean S, Bradley K, Campos SM, Cho KR, Chon HS, Chu C, Clark R, Cohn D, et al. Cervical Cancer, Version 32019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2019;17:64–84.CrossRefPubMed
41.
Kato T, Takashima A, Kasamatsu T, Nakamura K, Mizusawa J, Nakanishi T, Takeshima N, Kamiura S, Onda T, Sumi T, et al. Clinical tumor diameter and prognosis of patients with FIGO stage IB1 cervical cancer (JCOG0806-A). Gynecol Oncol. 2015;137:34–9.CrossRefPubMed
42.
Iglesias-Gato D, Wikström P, Tyanova S, Lavallee C, Thysell E, Carlsson J, Hägglöf C, Cox J, Andrén O, Stattin P, et al. The Proteome of Primary Prostate Cancer. Eur Urol. 2016;69:942–52.CrossRefPubMed
Metadata
Title
Identification of COPA as a potential prognostic biomarker and pharmacological intervention target of cervical cancer by quantitative proteomics and experimental verification
Authors
Huiqiong Bao
Xiaobin Li
Zhixing Cao
Zhihong Huang
Li Chen
Mingbing Wang
Jiali Hu
Wenting Li
Hongwei Sun
Xue Jiang
Ping Mei
Huawen Li
Ligong Lu
Meixiao Zhan
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-021-03218-1

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