A tumor microenvironment-associated circRNA predictor for tumor relapse and chemotherapy vulnerability in nasopharyngeal carcinoma

Ye-Lin Liang; Yu-Heng Zhao; Cong Ding; Sai-Wei Huang; Qian Li; Chong-Mei Zhu; Qing-Mei He; Ling-Long Tang; Yan-Ping Mao; Lei Chen; Wen-Fei Li; Guan-Qun Zhou; Na Liu; Wei Jiang; Jun Ma; Ying-Qin Li

doi:10.1016/j.isci.2023.108467

A tumor microenvironment-associated circRNA predictor for tumor relapse and chemotherapy vulnerability in nasopharyngeal carcinoma

iScience. 2023 Nov 14;26(12):108467. doi: 10.1016/j.isci.2023.108467. eCollection 2023 Dec 15.

Authors

Ye-Lin Liang^{1

2}, Yu-Heng Zhao^{1

3}, Cong Ding^{1

2}, Sai-Wei Huang^{1

2}, Qian Li^{1

2}, Chong-Mei Zhu^{1

4}, Qing-Mei He², Ling-Long Tang^{1

2}, Yan-Ping Mao^{1

2}, Lei Chen^{1

2}, Wen-Fei Li^{1

2}, Guan-Qun Zhou^{1

2}, Na Liu^{1

3}, Wei Jiang⁵, Jun Ma^{1

2

6}, Ying-Qin Li^{1

3}

Affiliations

¹ Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Center for Precision Medicine of Sun Yat-sen University, Guangzhou 510060, P.R. China.
² Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.
³ Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.
⁴ Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.
⁵ Department of Radiation Oncology, Affiliated Hospital of Guilin Medical University; Key Laboratory of Oncology (Guilin Medical University), Education Department of Guangxi Zhuang Autonomous Region, Guilin, China.
⁶ Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, P.R. China.

Abstract

Accurate risk stratification for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) is crucial for prognosis and treatment decisions. Here, we develop a tumor microenvironment-associated circular RNA (circRNA) signature that can stratify LA-NPC patients with different risks of relapse and vulnerability to induction chemotherapy (IC). Relapsed-related circRNAs are identified by comparing expression profiles between patients with and without relapse, followed by quantitative validation in the training cohort (n = 170). A nine-circRNA signature is constructed to classify patients into high-risk and low-risk groups. Low-risk patients have significantly favorable clinical survivals, which is validated in the internal (n = 170) and external (n = 150) cohorts. They are characterized by an immune-active microenvironment and can derive benefits from IC. Meanwhile, high-risk patients characterized with pro-relapse and DNA repair-associated features, are vulnerable to chemoresistance. Overall, the circRNA-based classifier serves as a reliable prognostic tool and might guide chemotherapy decisions for patients with LA-NPC.

Keywords: Biological sciences; Cancer; Health sciences; Internal medicine; Medical specialty; Medicine; Natural sciences; Oncology; Systems biology.