Colorectal cancer (CRC) is thought to be closely related to lifestyle modifiers and age. The role of underlying genetic determinants has been proposed in some studies. Among the hereditary genetic abnormalities linked with CRC is familial adenomatous polyposis, which often emerges as a benign polyp but might gradually transform into a cancerous lesion [1, 2]. The CRC might be diagnosed by colonoscopy and pathologic examination. In addition, imaging studies might assist in distinguishing other organ involvement. Screening is effective in the prevention and reduction of mortality from CRC and is recommended for average-risk individuals with no family history of CRC initiated since 50 years of age. If there are small polyps in colonoscopy, they might be resected. Furthermore, biopsies are conducted for large polyps or tumors to check if the lesion is malignant [3, 4].
In most cases of CRC, an adenoma is initially detected, which subsequently transforms into carcinoma. Cancer progression can be effectively thwarted if these precancerous lesions are timely detected and resected, which requires CRC screening and diagnosis at early stages . In 70% of sporadic cases of CRC, the lesions have been noted to develop from adenomatous polyps. In 25-30% of CRCs, sessile serrated lesions (SSLs) are the origin of cancer through the SSL-to-carcinoma pathway .
Screening for CRC is required for the diagnosis of this cancer at early stages and the initial detection and then removal of adenomas and SSLs. There are various screening tools available to detect adenomatous polyps, from computed tomography colonography and colonoscopy to sigmoidoscopy. In addition, stool-based testing (e.g., occult blood test) can be used to early detect cancerous changes. Colonoscopy is the preferred method to identify SSLs . Studies are also seeking to find noninvasive and inexpensive molecular methods for CRC screening. Among these, recent research on CRC has established a link between the patient’s clinical and pathological conditions and several molecular and genetic markers [8, 9].
Recent research has shown that different clinical, histological, and molecular parameters can be valuable prognostic markers for CRC, which can also be used for the diagnosis and treatment of this cancer. The clinical value of these factors might be variable. For example, well-known histopathological markers are used to classify malignancies into distinct subtypes. On the other hand, the biological characteristics of tumors can be used to predict disease progression and choose appropriate therapeutic approaches. Recent studies have shown that molecular biomarkers can be promising tools for the better management of cancers [10, 11]. Among these molecular markers are small non-coding ribonucleic acids (RNAs). Previous studies have shown that these RNAs are aberrantly expressed in numerous malignant human tumors, including the prostate, colon, breast, bladder, liver, and brain tumors [12, 13]. The miR-31 is involved in the migration and invasion in breast and colorectal cancers [14, 15]. In CRC, miR-31 activates the RAS signaling pathway by inhibiting the RAS p21 GTPase activating protein 1. This property confers cancer cell growth and stimulates tumorigenesis. High expression of miR-31 is correlated with advanced disease and the worst clinical outcome in metastatic CRC 
Humans’ RAS genes (i.e., Kirsten rat sarcoma virus [KRAS], NRAS, and HRAS) are the most commonly mutated oncogenes in cancers, identified in 90% of pancreatic cancers, 35% of lung cancers, and 45% of CRCs . The KRAS gene encodes KRAS, a protein acting in the downstream signaling pathways originated from the epidermal growth factor receptor (EGFR) . Upon the interaction of the mentioned receptor with its ligand, the PI3K/AKT/MTOR signaling route is activated, inducing cellular proliferation .
The basis of the molecular pathogenesis of CRC is not well known and more molecular tests are needed to investigate the genes related to this disease. Also, if more detailed molecular pathways are discovered, more molecular treatments could be evaluated. Today, the treatment approaches are going to target malignant cells via genetic pathways to protect normal cells from the adverse effects of drugs. Therefore future studies should be focused on molecular tests.
The present study investigated two molecular markers (i.e., miR-31 and miR-373) involved in the pathogenesis of CRC and their association with demographic characteristics of patients, disease status, and histopathological features. In addition, the prognostic value of these molecular markers was investigated in CRC patients with or without common KRAS mutations.
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