Identification of novel biomarkers affecting the metastasis of colorectal cancer through bioinformatics analysis and validation through qRT-PCR

Wenping Lian; Huifang Jin; Jingjing Cao; Xinyu Zhang; Tao Zhu; Shuai Zhao; Sujun Wu; Kailu Zou; Xinyun Zhang; Mingliang Zhang; Xiaoyong Zheng; Mengle Peng

doi:10.1186/s12935-020-01180-4

Identification of novel biomarkers affecting the metastasis of colorectal cancer through bioinformatics analysis and validation through qRT-PCR

Cancer Cell Int. 2020 Mar 30:20:105. doi: 10.1186/s12935-020-01180-4. eCollection 2020.

Authors

Wenping Lian^#¹, Huifang Jin^#², Jingjing Cao³, Xinyu Zhang⁴, Tao Zhu⁵, Shuai Zhao¹, Sujun Wu¹, Kailu Zou⁶, Xinyun Zhang⁷, Mingliang Zhang⁸, Xiaoyong Zheng⁹, Mengle Peng¹

Affiliations

¹ Department of Clinical Laboratory, Henan No. 3 Provincial People's Hospital, Zhengzhou, 450006 Henan China.
² 2Department of Blood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 Henan China.
³ Department of Basis Medicine, Henan Medical College, Zhengzhou, 451191 Henan China.
⁴ Department of Medical Affair, Henan No. 3 Provincial People's Hospital, Zhengzhou, 450006 Henan China.
⁵ Department of Clinical Laboratory, Zhecheng People's Hospital, Shangqiu, 476000 Henan China.
⁶ 6Medical College of Zhengzhou University, Zhengzhou, 450052 Henan China.
⁷ Department of Anorectal Surgery, Henan No. 3 Provincial People's Hospital, Zhengzhou, 450006 Henan China.
⁸ 8Henan Province Engineering Laboratory for Clinical Evaluation Technology of Chinese Medicine, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, 450000 China.
⁹ Department of Digestion, Henan No. 3 Provincial People's Hospital, Zhengzhou, 450006 Henan China.

^# Contributed equally.

Abstract

Background: Tumor progression and distant metastasis are the main causes of deaths in colorectal cancer (CRC) patients, and the molecular mechanisms in CRC metastasis have not been completely discovered.

Methods: We identified differentially expressed genes (DEGs) and lncRNAs (DELs) of CRC from The Cancer Genome Atlas (TCGA) database. Then we conducted the weighted gene co-expression network analysis (WGCNA) to investigate co-expression modules related with CRC metastasis. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, DEG-DEL co-expression network and survival analyses of significant modules were also conducted. Finally, the expressions of selected biomarkers were validated in cell lines by quantitative real-time PCR (qRT-PCR).

Results: 2032 DEGs and 487 DELs were involved the construction of WGCNA network, and greenyellow, turquoise and brown module were identified to have more significant correlation with CRC metastasis. GO and KEGG pathway analysis of these three modules have proven that the functions of DEGs were closely involved in many important processes in cancer pathogenesis. Through the DEG-DEL co-expression network, 12 DEGs and 2 DELs were considered as hub nodes. Besides, survival analysis showed that 30 DEGs were associated with the overall survival of CRC. Then 10 candidate biomarkers were chosen for validation and the expression of CA2, CHP2, SULT1B1, MOGAT2 and C1orf115 were significantly decreased in CRC cell lines when compared to normal human colonic epithelial cells, which were consistent with the results of differential expression analysis. Especially, low expression of SULT1B1, MOGAT2 and C1orf115 were closely correlated with poorer survival of CRC.

Conclusion: This study identified 5 genes as new biomarkers affecting the metastasis of CRC. Besides, SULT1B1, MOGAT2 and C1orf115 might be implicated in the prognosis of CRC patients.

Keywords: Biomarker; Colorectal cancer; Metastasis; Prognosis; WGCNA.