Plasma exosome-derived circGAPVD1 as a potential diagnostic marker for colorectal cancer

Tiankang Li; Tingting Zhou; Jin Wu; Heng Lv; Hui Zhou; Mingnan Du; Xiuzhong Zhang; Nai Wu; Shuai Gong; Zeqiang Ren; Pengbo Zhang; Chong Zhang; Guangpu Liu; Xin Liu; Yi Zhang

doi:10.1016/j.tranon.2023.101652

Plasma exosome-derived circGAPVD1 as a potential diagnostic marker for colorectal cancer

Transl Oncol. 2023 May:31:101652. doi: 10.1016/j.tranon.2023.101652. Epub 2023 Mar 17.

Authors

Tiankang Li¹, Tingting Zhou², Jin Wu¹, Heng Lv¹, Hui Zhou³, Mingnan Du⁴, Xiuzhong Zhang⁴, Nai Wu⁴, Shuai Gong⁴, Zeqiang Ren⁴, Pengbo Zhang⁴, Chong Zhang⁴, Guangpu Liu⁵, Xin Liu⁶, Yi Zhang⁷

Affiliations

¹ Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China; Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, China.
² Department of Endocrinology, The Affiliated Hospital of China University of Mining and Technology, Xuzhou, China; Department of Endocrinology, Xuzhou first People's Hospital, Xuzhou, China.
³ Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha 410013, China.
⁴ Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
⁵ Department of Spinal Surgery, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, China.
⁶ Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, China; Department of Endocrinology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. Electronic address: 489507198@qq.com.
⁷ Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China; Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, China. Electronic address: dr_zhy@xzhmu.edu.cn.

Abstract

Although circular RNAs (circRNAs) have recently garnered interest as disease markers, they have been relatively poorly studied as a biomarker in colorectal cancer (CRC). In this study, we aimed to screen the exosome-derived circRNAs in CRC and explore their potential as diagnostic and prognostic biomarkers of CRC METHODS: Exosomes were extracted from the plasma using a kit and validated by immunoblotting, transmission electron microscopy, and particle size analysis. The microarray datasets were employed to identify differentially-expressed circRNAs from plasma exosomes. Real-time quantitative reverse transcription PCR (RT-qPCR) verified the results of the microarray analysis, and Receiver operating characteristic (ROC) curve revealed the diagnostic ability of a single circRNA. The Starbase combined with microT, miRmap, and RNA22 were used to establish a circRNA-miRNA-mRNA network. Gene ontology, Kyoto Encyclopedia of Genes, Genomes pathway enrichment analysis, and Gene Set Enrichment Analysis were applied to determine potential functions of the identified mRNAs RESULTS: Comparing the microarray of plasma exosome-derived circRNAs and the microarray downloaded from the GEO database, 15 candidate circRNAs with up-regulated expression were identified. RT-qPCR verified that hsa_circ_0003270 (circGAPVD1) was upregulated in CRC plasma exosomes. ROC analysis showed that circGAPVD1 in plasma exosomes has potential diagnostic value for CRC. The sensitivity and specificity of circGAPVD1 in the diagnosis of CRC were found to be 75.64 and 71.79%, respectively (area under ROC = 0.7662). Furthermore, the lymph node metastasis and TNM staging of patients were positively correlated with high expression of circGAPVD1. Combined with the ENCORI database and GEO datasets, we identified the circGAPVD1-related ceRNA network. The enrichment analysis revealed that key nodes in the ceRNA network participate in many important signaling pathways such as protein post-translational modifications CONCLUSION: Our results revealed the diagnostic efficiency of circGAPVD1 in plasma exosomes. The highly expressed circGAPVD1 is expected to be a novel diagnostic marker for CRC.

Keywords: Biomarkers; Circular RNA; Colorectal cancer; Diagnosis; Exosomes; ceRNA network.