Loss of CHGA Protein as a Potential Biomarker for Colon Cancer Diagnosis: A Study on Biomarker Discovery by Machine Learning and Confirmation by Immunohistochemistry in Colorectal Cancer Tissue Microarrays

生物标志物 结直肠癌 生物标志物发现 组织微阵列 癌症 免疫组织化学 微阵列 医学 生物信息学 生物 肿瘤科 病理 蛋白质组学 内科学 基因 基因表达 遗传学
作者
Xueli Zhang,Zhiwu Hong,Cheng Fan,Camilla Hildesjö,Bairong Shen,Xiao‐Feng Sun
出处
期刊:Cancers [Multidisciplinary Digital Publishing Institute]
卷期号:14 (11): 2664-2664 被引量:5
标识
DOI:10.3390/cancers14112664
摘要

Background. The incidence of colorectal cancers has been constantly increasing. Although the mortality has slightly decreased, it is far from satisfaction. Precise early diagnosis for colorectal cancer has been a great challenge in order to improve patient survival. Patients and Methods. We started with searching for protein biomarkers based on our colorectal cancer biomarker database (CBD), finding differential expressed genes (GEGs) and non-DEGs from RNA sequencing (RNA-seq) data, and further predicted new biomarkers of protein–protein interaction (PPI) networks by machine learning (ML) methods. The best-selected biomarker was further verified by a receiver operating characteristic (ROC) test from microarray and RNA-seq data, biological network, and functional analysis, and immunohistochemistry in the tissue arrays from 198 specimens. Results. There were twelve proteins (MYO5A, CHGA, MAPK13, VDAC1, CCNA2, YWHAZ, CDK5, GNB3, CAMK2G, MAPK10, SDC2, and ADCY5) which were predicted by ML as colon cancer candidate diagnosis biomarkers. These predicted biomarkers showed close relationships with reported biomarkers of the PPI network and shared some pathways. An ROC test showed the CHGA protein with the best diagnostic accuracy (AUC = 0.9 in microarray data and 0.995 in RNA-seq data) among these candidate protein biomarkers. Furthermore, immunohistochemistry examination on our colon cancer tissue microarray samples further confirmed our bioinformatical prediction, indicating that CHGA may be used as a potential biomarker for early diagnosis of colon cancer patients. Conclusions. CHGA could be a potential candidate biomarker for diagnosing earlier colon cancer in the patients.
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