Alternative Spliced Variants as Biomarkers of Colorectal Cancer

Abstract

Surgical resection and adjuvant therapy, which mainly involves 5-fluorouracil (5-FU), irinotecan (CPT-11), oxaliplatin (LOHP) chemotherapy and recently targeted therapy, are the most common treatments of colorectal cancer (CRC). As to improve the therapeutic efficacy and assist with therapeutic decisions, there is an urgent need for prognostic and predictive molecular biomarkers. Recent evidence demonstrates that aberrations in alternative splicing process of cancer will provide candidate biomarkers for cancers to meet this need. In this review, we outline the fundamental mechanism of alternative splicing that plays a major role in protein diversity, and summarize the relationship between imbalance alternative splicing with cancer. Moreover, several alternative spliced variants and cancer-specific splicing events at the mRNA level in CRC, which may serve as diagnostic, predictive, prognostic markers of CRC, are also discussed. These specific splice variants or the RNA splicing machinery will be new, potential targets for the treatment of CRC that offers a specific site of anti-cancer chemotherapy.

A New Exon Derived from a Mammalian Apparent LTR Retrotransposon of theSUPT16HGene

“…However, alternatively spliced variants can be stabilized and increased without selection, and exonization can lead to not only transcriptome diversity but also proteome diversity [2, 10]. Furthermore, these events occur differently or specifically according to the tissue, developmental stage, and disease; thus, alternative transcripts are used to mine disease diagnostic markers [9, 26]. …”

Characterization of lacrimal proline‐rich protein 4 (PRR4) in human tear proteome

“…Establishments of techniques to identify PRR4 isoforms as presented herein is the first important step for further quantifications of the protein in the disease state, followed by determination of the functional consequences. Protein isoforms can play important roles in various biological processes and can potentially be used as biomarkers or therapeutic targets/mediators . For example, studies by Shokeer and Mannervik demonstrated that one of the factors new functions can develop in an enzyme is through point mutation .…”

Alternative Splicing for Diseases, Cancers, Drugs, and Databases

“…Reported examples include p53 and PTEN [30], kallikrein-related peptidase 12 (KLK12) [31], breast cancer early-onset 1 (BRCA1) [32], protein N-arginine methyltransferases 2 (PRMT2) [33], and CDC25 phosphatases [34] in breast cancer; lysyl oxidase-like 4 (LOXL4) [35] and growth factor receptor-bound protein 7 (GRB7) in ovarian cancer [36]; androgen receptor in prostate cancer [37]; tissue inhibitor of metalloproteinases-1 (TIMP1) and the cell adhesion molecule CD44 in colon cancer [38, 39]; Bcl-xL, CD44, and others in lung cancer [40]; calpain 3 in melanoma [41]; and Krüppel-like factor 6 (KLF6) in liver cancer [42]. Therefore, alternative spliced variants are potential biomarkers [43, 44] for the cancer diagnosis/prognosis and may be the targets for cancer therapy based on specific splicing correction treatments.…”