Prognostic Value of APOBEC3A in Patients with Cervical Squamous Cell Carcinoma in a Major Urban Center in China: a Retrospective Study

Overview

Journal Transl Cancer Res

Specialty Oncology

Date 2023 Nov 16

PMID 37969401

Authors

Haiwei He

Shenglian Lu

Nan Lu

Nian Huang

Mingjuan Xu

Affiliations

Soon will be listed here.

Abstract

Background: APOBEC3A (A3A) has been implicated to have vital prognostic value in several common cancers. This study aimed to investigate the prognostic value of A3A expression in cervical squamous cell carcinoma (CESC).

Methods: This retrospective study enrolled 59 patients with CESC or cervical squamous intraepithelial neoplasia from January 2014 to January 2017 in Changhai Hospital, Naval Medical University. Then, A3A histoscores (H-scores) using immunohistochemistry (IHC) were analyzed in formalin-fixed paraffin-embedded archival tissue blocks. Moreover, overall survival was analyzed by the Kaplan-Meier method.

Results: The H-score of A3A protein expression was relatively higher in CESC than in squamous intraepithelial neoplasia, and the relative expression level of normal cervical tissues was lower than that of cervical squamous intraepithelial neoplasia (P<0.001). Moreover, the H-score of poorly differentiated cases was 6, which was higher than that of moderately differentiated cases (H-score =3), while the H-score of well-differentiated cases was 2, which was lower than that of moderately differentiated cases. Moreover, patients in the A3A low expression group had higher overall survival rates by prognostic analysis (P=0.027).

Conclusions: A3A protein expression was increased during CESC progression. Moreover, A3A expression was tightly related to poor prognosis in CESC. Thus, these results showed that A3A overexpression may provide a marker for poor prognosis in CESC.

References

Argyris P, Wilkinson P, Jarvis M, Magliocca K, Patel M, Vogel R . Endogenous APOBEC3B overexpression characterizes HPV-positive and HPV-negative oral epithelial dysplasias and head and neck cancers. Mod Pathol. 2020; 34(2):280-290. PMC: 8261524. DOI: 10.1038/s41379-020-0617-x. View

Li J, Chen Y, Guo X, Bai X, Xu X, Han T . lncNBAT1/APOBEC3A is a mediator of HBX-induced chemoresistance in diffuse large B cell lymphoma cells. Mol Ther Nucleic Acids. 2022; 27:1064-1077. PMC: 8850662. DOI: 10.1016/j.omtn.2022.01.015. View

Farmanbar A, Firouzi S, Kneller R, Khiabanian H . Mutational signatures reveal ternary relationships between homologous recombination repair, APOBEC, and mismatch repair in gynecological cancers. J Transl Med. 2022; 20(1):65. PMC: 8812249. DOI: 10.1186/s12967-022-03259-0. View

Joura E, Giuliano A, Iversen O, Bouchard C, Mao C, Mehlsen J . A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med. 2015; 372(8):711-23. DOI: 10.1056/NEJMoa1405044. View

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

DeWeerd R, Nemeth E, Poti A, Petryk N, Chen C, Hyrien O . Prospectively defined patterns of APOBEC3A mutagenesis are prevalent in human cancers. Cell Rep. 2022; 38(12):110555. PMC: 9283007. DOI: 10.1016/j.celrep.2022.110555. View

Zacharakis N, Chinnasamy H, Black M, Xu H, Lu Y, Zheng Z . Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer. Nat Med. 2018; 24(6):724-730. PMC: 6348479. DOI: 10.1038/s41591-018-0040-8. View

Barka A, Berrios K, Bailer P, Schutsky E, Wang T, Kohli R . The Base-Editing Enzyme APOBEC3A Catalyzes Cytosine Deamination in RNA with Low Proficiency and High Selectivity. ACS Chem Biol. 2022; 17(3):629-636. PMC: 9949940. DOI: 10.1021/acschembio.1c00919. View

Xu F, Liu T, Zhou Z, Zou C, Xu S . Comprehensive Analyses Identify APOBEC3A as a Genomic Instability-Associated Immune Prognostic Biomarker in Ovarian Cancer. Front Immunol. 2021; 12:749369. PMC: 8568129. DOI: 10.3389/fimmu.2021.749369. View

10.

Green A, Weitzman M . The spectrum of APOBEC3 activity: From anti-viral agents to anti-cancer opportunities. DNA Repair (Amst). 2019; 83:102700. PMC: 6876854. DOI: 10.1016/j.dnarep.2019.102700. View

11.

Law E, Levin-Klein R, Jarvis M, Kim H, Argyris P, Carpenter M . APOBEC3A catalyzes mutation and drives carcinogenesis in vivo. J Exp Med. 2020; 217(12). PMC: 7953736. DOI: 10.1084/jem.20200261. View

12.

Alexandrov L, Nik-Zainal S, Wedge D, Aparicio S, Behjati S, Biankin A . Signatures of mutational processes in human cancer. Nature. 2013; 500(7463):415-21. PMC: 3776390. DOI: 10.1038/nature12477. View

13.

Wakae K, Nishiyama T, Kondo S, Izuka T, Que L, Chen C . Keratinocyte differentiation induces APOBEC3A, 3B, and mitochondrial DNA hypermutation. Sci Rep. 2018; 8(1):9745. PMC: 6021414. DOI: 10.1038/s41598-018-27930-z. View

14.

Liu W, Ji H, Zhao J, Song J, Zheng S, Chen L . Transcriptional repression and apoptosis influence the effect of APOBEC3A/3B functional polymorphisms on biliary tract cancer risk. Int J Cancer. 2022; 150(11):1825-1837. DOI: 10.1002/ijc.33930. View

15.

Huang R, Haberberger J, Murugesan K, Danziger N, Hiemenz M, Severson E . Clinicopathologic and genomic characterization of PD-L1-positive uterine cervical carcinoma. Mod Pathol. 2021; 34(7):1425-1433. DOI: 10.1038/s41379-021-00780-3. View

16.

Schlichte M, Guidry J . Current Cervical Carcinoma Screening Guidelines. J Clin Med. 2015; 4(5):918-32. PMC: 4470206. DOI: 10.3390/jcm4050918. View

17.

Liu J, Ho J, Lee J, Hur S, Yoo J, Kim K . Genomic, transcriptomic, and viral integration profiles associated with recurrent/metastatic progression in high-risk human papillomavirus cervical carcinomas. Cancer Med. 2020; 9(21):8243-8257. PMC: 7643681. DOI: 10.1002/cam4.3426. View

18.

Zhu B, Xiao Y, Yeager M, Clifford G, Wentzensen N, Cullen M . Mutations in the HPV16 genome induced by APOBEC3 are associated with viral clearance. Nat Commun. 2020; 11(1):886. PMC: 7021686. DOI: 10.1038/s41467-020-14730-1. View

19.

Warren C, Xu T, Guo K, Griffin L, Westrich J, Lee D . APOBEC3A functions as a restriction factor of human papillomavirus. J Virol. 2014; 89(1):688-702. PMC: 4301161. DOI: 10.1128/JVI.02383-14. View

20.

Revathidevi S, Murugan A, Nakaoka H, Inoue I, Munirajan A . APOBEC: A molecular driver in cervical cancer pathogenesis. Cancer Lett. 2020; 496:104-116. PMC: 7539941. DOI: 10.1016/j.canlet.2020.10.004. View