Colorectal cancer is dangerous and a confirmed diagnosis is almost like a death sentence considering it is the third most common malignancy diagnosed in the human population. Colorectal cancer affects the rectum and colon parts of the large intestine and begins from the glandular epithelial cells when some of these cells develop a series of genetic mutations (Rawla et al., 2019). Following mutations, the cell begins to multiply abnormally and increase in number giving rise to a benign adenoma, which may gradually progress into carcinoma and spread to other body tissues. The aggressive nature of the cancer and it ability to spread to adjacent tissues drastically reduces survival rates. The cancer affects men more than women, and it is 3–4 times fold in developed compared to developing countries (Rawla et al., 2019). Globally, at least 861,000 deaths and 1.8 million new incidences were reported in 2018 (GLOBOCAN 2018). In the United States, colorectal cancer appears as number three in the scale of the most lethal cancers. Furthermore, from 1995-2016 the incidence of colorectal cancer in American men and women below the age of 50 gradually rose at a rate of 2% (Siegel et al., 2020). In America the 5-year survival rate for patients with an early diagnosis is 90% but the survival rate drastically reduces up to 14% for late diagnosis. (American Cancer Society, 2020). Globally, the survival rate has also increased owing to better early screening and better treatments (Rawla et al., 2019).
The Cancer Genome Atlas (TCGA) colonic adenocarcinoma, (TCGA-COAD) and TCGA rectal adenocarcinoma (TCGA-READ) provide molecular knowledge of colorectal cancer. Data collection began in 2006 until 2012 when enough samples were accrued for processing. The samples were collected from all over the world through tissue source sites which include hospitals and health research centres in America, Europe, Asia, South America and Africa. The project used 276 samples and investigated exome patterns, DNA duplicate number, promoter methylation, and the expression of mRNA and microRNA (Cancer Genome Atlas Network (2012). Two hundred two colon samples and 75 rectum samples were analyzed. The age average of the individuals whose samples were analyzed in TCGA-COAD was 66.9, while TCGA-READ was 64.5 (Wang et al., 2018). In terms of race, TCGA-COAD had 215 whites, 59 blacks, and 11 from other ethnicities. TCGA-READ had 82 whites, six blacks, and one under other categories. There were slightly more males than females in both COAD and READ. The project identified more than 94% mutations in one or several members of the WNT signalling pathway.
Krüppel-like factor 5 (KLF5): plays an important function in controlling the growth of typical intestinal epithelial cells as well as colorectal cancer cells. Increased expression of KLF5 is associated with poor prognosis hence reduced survival rate of the patients with colorectal cancer (Tagaki et al., 2020). The mutation in the zinc finger transcription factor makes it difficult for the FBW7α to degrade it (Bialkowska et al., 2014). It promotes the growth of cancer stem like cells.
Ets2 gene: This gene has been identified as significant in the Wnt signaling pathway associated with the development of colorectal cancer. The expression of Ets2 occurs within intestinal crypts. The lack of Ets2 leads to elevated growth at the base of colon crypts. Impaired regulation Ets2 promotes cell proliferation in cancers, invasion and metastasis by activating gene transcription (Fry & Inoue, 2018). The gene is associated with poor survival rate and prognosis in patients with colorectal cancer.
SMAD2: This gene plays an important role in the transforming growth factor, TGF-β signaling pathway, which provides proliferation inhibitory signals in the typical intestinal epithelial cells (Jung et al., 2017). The lack of SMAD2 expression is associated with the spread of colorectal cancers and a reduced survival rate with a poor prognosis (Xie et al., 2003).
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