The use of micro RNA in the early detection of cervical intraepithelial neoplasia

Abstract

An important issue in current oncological research is prevention as well as early detection of cancer. This includes also the difficulty to predict the progression of early or pre-cancerous lesions to invasive cancer. In this context, the characterization and categorization of pre-neoplastic lesions of squamous cell carcinoma [cervical intraepithelial neoplasia (CIN)] are an important task with major clinical impact. Screening programs are worldwide established with the aim to detect and eradicate such lesions with the potential to develop untreated into cervical cancer. From the literature it is known that around 5% of CIN 2 and 12% of CIN 3 cases will progress to cancer. The use of molecular markers extracted from cervical mucus might help to identify these high-risk cases and to exclude unnecessary biopsies or surgical treatment. Here we can show that micro RNA (miRNA) analysis from cervical mucus of 49 patients allowed us to distinguish between healthy patients and patients with CIN 3. The miRNA panel used in combination allowed for highly significant testing (P < 0.0001) of CIN 3 status. In parallel, the human papillomavirus status of the patients, the most important factor for the development of cervical cancer, significantly correlated with the miRNA markers hsa-miR-26b-5p, hsa-miR-191-5p and hsa-miR-143-3p, a subpanel of the original six miRNAs. We provide here a proof-of-concept for cervical mucus-based testing for pre-neoplastic stages of cervical squamous cell carcinoma.

Expression of GMFB in High-Grade Cervical Intraepithelial Neoplasia and Its Role in Cervical Cancer

“…Previous paper [ 19 ] has discovered that miR-143-3p, miR-26b-5p, miR-191-5p, and miR-223-3p could serve as the biomarkers of CIN. miRDB was used to predict their common target, and it turned out that GMFB was targeted by these miRNAs in common ( Figure 1(a) ).…”

“… GMFB is targeted by miR-143-3p, miR-26b-5p, miR-191-5p, and miR-223-3p (a) miRNAs listed in previous paper [ 19 ] and their common target GMFB predicted by miRDB. (b) Binding sites between GMFB and corresponding miRNAs predicted by miRDB.…”

“…miR-411 hinders CC progression via binding to STAT3 [ 16 ]. In 2020, as miRNAs evolved into a versatile tool to distinguish genetical differences of cellular product [ 17 , 18 ] and a diagnostic marker for various types of cancer, Wittenborn et al discovered that a subpanel of six miRNAs (hsa-miR-26b-5p, hsa-miR-142-3p, hsa-miR-143-3p, hsa-miR-191-5p, hsa-miR-223-3p, and has-miR-338-3p) marked the CIN progress process and early stages of cervical squamous cell carcinoma [ 19 ]. Therefore, we set about investigation from the common target gene of these 6 miRNA markers and found that GMFB was targeted by miR-143-3p, miR-26b-5p, miR-191-5p, and miR-223-3p in common.…”

A Glimmer of Hope for Patients with a T3 Transformation Zone: miRNAs Are Potential Biomarkers for Cervical Dysplasia

“…Based on the extensive literature research and personal experiences in the detection of miRNAs in cervical mucus and other body fluids, we selected eight miRNAs to be tested on patient CMS [23,29]. Hsa-miR-26b-5p, hsa-miR-142-3p, hsa-miR-143-3p, hsa-miR-191-5p, hsa-miR-223-3p, hsa-miR-338-3p, hsa-miR-205-5p, and hsa-miR-130a-3p were subsequently analyzed in a total of 63 patients.…”

“…Aberrant expression of miRNAs in cervical cancer and its precursor lesions have been studied before and have shown potential in distinguishing even the different CIN types [29].…”