All over the world, colon cancer is estimated to be the 2nd most common type of cancer in females (614,000 cases representing ~ 9.2% of all cancers) and the 3rd most common type in males (746,000 cases representing ~ 10.0% of the total). Early detection of patients with cancer has a favorable outcome with treatment, with the 5-year survival rates exceeding 70%. For several decades, colonoscopy has been used as the first choice for screening of early-stage colon cancer; but because of its invasive character, patients show low compliance in the clinical setting. Thus, cost-effective and non-invasive biomarkers with high sensitivity and specificity are essentially required to help early detection of colon cancer [1].
Recently detected microRNAs (miRNAs) are endogenous, small, non-coding evolutionarily conserved RNA (~ 22–25 nucleotide length), also referred as micro-coordinators of gene expression that have been revealed to be an efficient method to study the biology of various diseases and to be used as a novel diagnostic and prognostic biomarkers with a great level of specificity and sensitivity. Additionally, miRNAs are characterized by a high degree of stability so they could be isolated from body fluids and tissues and can be measured easily [2].
MiRNAs are incorporated in various biological pathways that may affect tumorigenesis and progression and also may function as oncogenes or tumor suppressors, based on the downstream effects produced by the affected miRNA. Although the miRNA function is not completely understood yet, they have been accompanied by various important molecular pathways that have been related to carcinogenesis and tumor progression as proved by multiple experimental models and clinical studies that were carried out on different types of cancer, including colon cancer [2].
MiRNAs have been assumed to be a potential reliable biomarker for screening of cancer because they are highly stable and can be measured easily using the common laboratory methods. In 2015, Kara et al. [3] conducted a study aiming to evaluate the expression profile of some cancer-related genes and their regulatory miRNA molecules. In this study, they used a high-throughput real-time PCR method on 54 colon cancer patients and normal colon tissue samples of 42 healthy controls. Their results revealed that a wide range of miRNA types, including miRNA-17-3p were significantly deregulated in colon cancer. They strongly concluded the possible involvement of novel cancer-related genes and their regulatory miRNAs in colon cancer physiopathology along with the probability of using this miRNA as a biomarker for early detection of colon cancer.
A lot of studies have thrown the light on the role of various biomarkers in the progression and diagnosis of colon cancer. These markers include CEA and CA19.9. Recently, the gene encoding CEA has been categorized as a member of the immunoglobulin supergene family that includes gene encoding for adhesion molecules as intercellular adhesion molecule 1(ICAM-1), major histocompatibility (MHC) antigen, and lymphocyte function-associated antigen [4].
The application of CEA as a marker for the diagnosing of colon cancer is limited because it is neither sensitive nor specific, mainly at the onset of the disease. At a cutoff of 2.5 μg/L, the range of sensitivity is about 30–80% according to the stage of the disease. But, as concluded by Fletcher, in symptomatic patients, the sensitivity of CEA is more elevated than asymptomatic subjects as the symptomatic group usually has more advanced disease [5].
CA19-9 is a Sialylated Lewis antigen of the MUC1 protein [6]. The American Society of Oncology does not encourage the use of CA19-9 because it is less sensitive in asymptomatic, non-advanced cases of colon cancer giving false negative results. Also, it is present in non-cancer cases (false positive) [7].
CA19-9 is less specific in colon cancer as it may be found in various types of tumors such as pancreatic, gastric cancers and hepatocellular carcinoma, as well as in benign cases such as bile duct diseases as obstruction of the bile duct. Besides, subjects who do not have the Lewis antigen “(a blood type antigen on RBCs) who represent approximately 10% of the Caucasian population,” do not express CA19-9, even if they have large tumors. This is due to a deficiency of a fucosyl transferase enzyme which is required for the production of CA19-9 and the Lewis antigen [7]. Both CEA and CA19-9 biomarkers are considered of prognostic value better than a diagnostic tool.
The present study aimed to investigate whether miR-17-3p is elevated in the blood of colon cancer patients with different stages and assess their role as a novel biomarker for this type of cancer, and if there is any role of this biomarker in staging in correlation with other well-known tumor markers (CEA, CA19.9).