Abstract
Colorectal cancer (CRC) is one of the major causes of cancer death worldwide. In general, early diagnosis for CRC and individual therapy have led to better survival for the cancer patients. Accumulating studies concerning biomarkers have provided positive evidence to improve cancer early diagnosis and better therapy. It is, however, still necessary to further investigate the precise biomarkers for cancer early diagnosis and precision therapy and predicting prognosis. In this study, AI-assisted systems with bioinformatics algorithm integrated with microarray and RNA sequencing (RNA-seq) gene expression (GE) data has been approached to predict microRNA (miRNA) biomarkers for early diagnosis of CRC based on the miRNA-messenger RNA (mRNA) interaction network. The relationships between the predicted miRNA biomarkers and other biological components were further analyzed on biological networks. Bayesian meta-analysis of diagnostic test was utilized to verify the diagnostic value of the miRNA candidate biomarkers and the combined multiple biomarkers. Biological function analysis was performed to detect the relationship of candidate miRNA biomarkers and identified biomarkers in pathways. Text mining was used to analyze the relationships of predicted miRNAs and their target genes with 5-fluorouracil (5-FU). Survival analyses were conducted to evaluate the prognostic values of these miRNAs in CRC. According to the number of miRNAs single regulated mRNAs (NSR) and the number of their regulated transcription factor gene percentage (TFP) on the miRNA-mRNA network, there were 12 promising miRNA biomarkers were selected. There were five potential candidate miRNAs (miRNA-186-5p, miRNA-10b-5, miRNA-30e-5p, miRNA-21 and miRNA-30e) were confirmed as CRC diagnostic biomarkers, and two of them (miRNA-21 and miRNA-30e) were previously reported. Furthermore, the combinations of the five candidate miRNAs biomarkers showed better prediction accuracy for CRC early diagnosis than the single miRNA biomarkers. miRNA-10b-5p and miRNA-30e-5p were associated with the 5-FU therapy resistance by targeting the related genes. These miRNAs biomarkers were not statistically associated with CRC prognosis.
Highlights
Colorectal cancer (CRC) is one of the most common types of cancer and its incidence has been increasing during the last decades [1,2], and CRC is one of the major leading causes of Cancers 2020, 12, 341; doi:10.3390/cancers12020341 www.mdpi.com/journal/cancersCancers 2020, 12, 341 cancer death [1]
We have developed a software (MiRNA-BD) for miRNA biomarker prediction [20] and it has been used in several different diseases and predicted several useful miRNA biomarkers [21,22,23]
There were 222 identified CRC associated miRNAs which were collected from miRNet database as the foundations for further topology predictions to construct the CRC specific miRNA-messenger RNA (mRNA) network
Summary
Colorectal cancer (CRC) is one of the most common types of cancer and its incidence has been increasing during the last decades [1,2], and CRC is one of the major leading causes of Cancers 2020, 12, 341; doi:10.3390/cancers12020341 www.mdpi.com/journal/cancersCancers 2020, 12, 341 cancer death [1]. In the United States, there are around 145,600 newly-diagnosed CRC patients and. 51,020 cancer deaths in 2019, which are estimated by the America Cancer Society [2], and in China, the newly-diagnosed CRC and the cancer deaths are estimated as 521,490 and 245,263, respectively [3]. In the United Kingdom, there are 47,892 new CRC cases and 20,470 patient deaths [4], and in Sweden, the new cases and deaths are 6421 and 3022, respectively [5]. Fecal occult blood test and colonoscopy are currently believed as the most powerful tools to make the early diagnosis for CRC [6]. Since the fecal occult blood test leads to a rather high false-positive rate it cannot be considered as a specific teat for CRC early diagnosis
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