Significance of Dynamic Changes of VCA-IgA Levels in Pre- and Post-treatment Plasma of Patients with Nasopharyngeal Carcinoma: Development of a Clinically-Oriented Model

Overview

Journal Adv Ther

Date 2023 Mar 25

PMID 36964411

Authors

Minjie Mao

Hui Sheng

Boyu Tian

Peidong Chi

Kewei Huang

Huilan Li

Wen Liu

Affiliations

Soon will be listed here.

Abstract

Introduction: Nasopharyngeal carcinoma (NPC) responds well to radiotherapy but recurrence and metastasis are common. Currently, there is no widely used biomarker for accurately predicting the recurrence and metastasis of NPC. In this study, we aimed to evaluate the prognostic ability of Epstein-Barr virus (EBV) capsid antigen (VCA-IgA) kinetics by assessing the dynamic changes of VCA-IgA levels in the pre- and post-treatment plasma of patients with NPC and have proposed a prognostic model for clinical use.

Methods: The clinical records of patients with NPC diagnosed at Sun Yat-sen University Cancer Center were retrieved and classified into a respondent (n = 83) or non-respondent (n = 25) cohort based on their response to antitumor therapy. Factors associated with the outcomes of the patients were assessed and incorporated in a nomogram. For internal validation, bootstrapping with 1000 resamples was used. The prediction accuracy and discriminative ability of the nomogram were investigated by calibration and concordance index (C-index) and plotted decision curves to assess the benefits of nomogram-assisted decisions in a clinical context.

Results: Plasma VCA-IgA level of the non-respondent cohort at the 6th month after treatment was found significantly higher than the respondent cohort. Post-treatment VCA-IgA level, smoking, and distant metastases were identified as independent risk factors for disease-free survival (DFS), and were used to stratify patients with NPC into three risk groups. The median DFS of the low-, middle- and high-risk groups were 48.5, 35.0, and 15.5 months, respectively. The C-index of the nomogram was 0.848 (95% CI 0.769-0.926), demonstrating good clinical accuracy for predicting the DFS of patients with NPC. The decision curve showed that the nomogram in predicting DFS was better than VCA-IgA level, smoking, and distant metastases.

Conclusion: The proposed VCA-IgA-based nomogram demonstrated a promising ability to predict the DFS of patients with NPC after antitumor therapy. It could be used as a clinical guidance to improve the therapeutic/surveillance strategies of these patients.

References

Chen Y, Chan A, Le Q, Blanchard P, Sun Y, Ma J . Nasopharyngeal carcinoma. Lancet. 2019; 394(10192):64-80. DOI: 10.1016/S0140-6736(19)30956-0. View

Tan L, Tan G, Sivanesan V, Goh S, Ng X, Lim C . Systematic comparison of plasma EBV DNA, anti-EBV antibodies and miRNA levels for early detection and prognosis of nasopharyngeal carcinoma. Int J Cancer. 2019; 146(8):2336-2347. PMC: 7065012. DOI: 10.1002/ijc.32656. View

Wang Y, Zhang Y, Jiang W, Chen Y, Xu S, Liu N . Development and validation of an immune checkpoint-based signature to predict prognosis in nasopharyngeal carcinoma using computational pathology analysis. J Immunother Cancer. 2019; 7(1):298. PMC: 6854706. DOI: 10.1186/s40425-019-0752-4. View

Zhang Z, Huang J, Wang G, Jin F, Zheng J, Xiao H . Serum miRNAs, a potential prognosis marker of loco-regionally advanced nasopharyngeal carcinoma patients treated with CCRT. BMC Cancer. 2020; 20(1):183. PMC: 7057605. DOI: 10.1186/s12885-020-6689-7. View

Li W, Liu G, Lin L, Lv S, Qiang M, Lv X . MRI-detected residual retropharyngeal lymph node after intensity-modulated radiotherapy in nasopharyngeal carcinoma: Prognostic value and a nomogram for the pretherapy prediction of it. Radiother Oncol. 2020; 145:101-108. DOI: 10.1016/j.radonc.2019.12.018. View

Liu W, Li H, Sheng H, Liu X, Chi P, Wang X . A Randomized Controlled Trial on Evaluation of Plasma Epstein-Barr Virus Biomarker for Early Diagnosis in Patients With Nasopharyngeal Carcinoma. Adv Ther. 2020; 37(10):4280-4290. DOI: 10.1007/s12325-020-01461-4. View

Pauker S, Kassirer J . The threshold approach to clinical decision making. N Engl J Med. 1980; 302(20):1109-17. DOI: 10.1056/NEJM198005153022003. View

Camp R, Dolled-Filhart M, Rimm D . X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res. 2004; 10(21):7252-9. DOI: 10.1158/1078-0432.CCR-04-0713. View

Guan S, Wei J, Huang L, Wu L . Chemotherapy and chemo-resistance in nasopharyngeal carcinoma. Eur J Med Chem. 2020; 207:112758. DOI: 10.1016/j.ejmech.2020.112758. View

10.

Hao W, Wu L, Cao L, Yu J, Ning L, Wang J . Radioresistant Nasopharyngeal Carcinoma Cells Exhibited Decreased Cisplatin Sensitivity by Inducing SLC1A6 Expression. Front Pharmacol. 2021; 12:629264. PMC: 8077170. DOI: 10.3389/fphar.2021.629264. View

11.

Du T, Jiang J, Chen Y, Zhang N, Chen G, Wang X . MiR-138-1-3p alters the stemness and radiosensitivity of tumor cells by targeting CRIPTO and the JAK2/STAT3 pathway in nasopharyngeal carcinoma. Ann Transl Med. 2021; 9(6):485. PMC: 8039661. DOI: 10.21037/atm-21-521. View

12.

Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A . Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med. 2007; 13(9):1050-9. DOI: 10.1038/nm1622. View

13.

Chen L, Flies D . Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol. 2013; 13(4):227-42. PMC: 3786574. DOI: 10.1038/nri3405. View

14.

Zhang N, Hu C . Effect of PD-L1 and tumor regression rate on prognosis of nasopharyngeal carcinoma. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2022; 45(11):1276-1282. DOI: 10.11817/j.issn.1672-7347.2020.190367. View

15.

Adkins D, Haddad R . Clinical trial data of Anti-PD-1/PD-L1 therapy for recurrent or metastatic nasopharyngeal Carcinoma: A review. Cancer Treat Rev. 2022; 109:102428. DOI: 10.1016/j.ctrv.2022.102428. View

16.

Xu X, Lu R, Xiao R, Zhou L, Zhao X, Hu X . Rta-IgG as a biomarker for diagnosis and post treatment prognostic of nasopharyngeal carcinoma. Cancer Biomark. 2016; 16(3):467-76. DOI: 10.3233/CBM-160586. View

17.

Yan Y, Yang X, Sun X, Zhang H, Liu L, Ran R . Inhibitory effect of simiao qingwen baidu decoction on epstein-barr virus EA, VCA expression and DNA replication in vitro. Biomed Pharmacother. 2020; 131:110638. DOI: 10.1016/j.biopha.2020.110638. View

18.

Qu Y, Wang D, Yang L, Liu H, Cui W, Che Y . Expression and clinical significance of programmed death ligand 1 in nasopharyngeal carcinoma. Mol Clin Oncol. 2018; 9(1):75-81. PMC: 6030993. DOI: 10.3892/mco.2018.1633. View

19.

Yang M, Huang W . Circular RNAs in nasopharyngeal carcinoma. Clin Chim Acta. 2020; 508:240-248. DOI: 10.1016/j.cca.2020.05.029. View