J Cancer 2017; 8(12):2346-2355. doi:10.7150/jca.19465

Research Paper

Development and Validation of a Serum Biomarker Panel for the Detection of Esophageal Squamous Cell Carcinoma through RNA Transcriptome Sequencing

Shan Xing1,2†, Xin Zheng1,2†, Li-Qiang Wei4†, Shi-Jian Song5, Dan Liu1,3, Ning Xue1,3, Xiao-Min Liu1,2, Mian-Tao Wu1,2, Qian Zhong1,3, Chu-Mei Huang6, Mu-Sheng Zeng1,3✉, Wan-Li Liu1,2✉

1. State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
2. Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, Guangzhou, China
3. Department of Experimental Research, Sun Yat-sen University cancer center, Guangzhou, China
4. Department of Clinical Laboratory, Shaanxi Provincial People's Hospital, Xian, China
5. Guangdong Experimental High School, Guangzhou, China
6. Department of Laboratory Medicine, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China
† Xing S, Zheng X and Wei LQ contributed equally to this work

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Xing S, Zheng X, Wei LQ, Song SJ, Liu D, Xue N, Liu XM, Wu MT, Zhong Q, Huang CM, Zeng MS, Liu WL. Development and Validation of a Serum Biomarker Panel for the Detection of Esophageal Squamous Cell Carcinoma through RNA Transcriptome Sequencing. J Cancer 2017; 8(12):2346-2355. doi:10.7150/jca.19465. Available from http://www.jcancer.org/v08p2346.htm

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Serum tumor markers for the diagnosis of esophageal squamous cell carcinoma (ESCC) have low sensitivity. This study aims to identify new serum markers for ESCC diagnosis from RNA sequencing (RNA-seq) data.

RNA-seq was performed using six pairs of ESCC and matched normal tissues. The candidates for ESCC were screened from the differentially expressed genes. The candidates were analyzed by ELISA from the serum of a test group and a validation group. Real-time PCR, Western blotting and immunohistochemistry were used to detect the expression of the candidates in tumor cell lines and tumor tissues.

Ten genes were selected from the RNA-seq data. Serum levels of ADAM12, CHI3L1, MMP13 and SPP1 were significantly higher in the ESCC patients than in the healthy controls. A diagnostic model combining CHI3L1, MMP13, and SPP1 was established. The area under the curve (AUC) values for serum CHI3L1, MMP13, and SPP1 and the diagnostic model for discriminating ESCC patients from controls were 0.732, 0.881, 0.661 and 0.928, respectively. In the validation cohort, the AUC values were 0.753, 0.789, 0.696 and 0.843, respectively. Moreover, the AUC of the model for classifying patients with early ESCC was 0.918 in the test group and 0.857 in the validation group. Overexpression of CHI3L1, MMP13 and SPP1 was observed in the tumor cell lines and tissues.

The diagnostic model composed of CHI3L1, MMP13 and SPP1 discriminates ESCC patients with high sensitivity. Our data highlight the potential of this diagnostic model for the noninvasive diagnosis of ESCC.

Keywords: esophageal squamous cell carcinoma, RNA transcriptome sequencing, diagnostic biomarker, ESCC, early detection