Plasma microRNA Levels Combined with CEA and CA19-9 in the Follow-Up of Colorectal Cancer Patients

Abstract

Colorectal cancer (CRC) ranks among the most common cancers worldwide. Surgical removal remains the best strategy for treatment of resectable tumors. An important part of caring for patients after surgery is monitoring for early detection of a possible relapse of the disease. Efforts are being made to improve the sensitivity and specificity of routinely used carcinoembryonic antigen (CEA) with the use of additional biomarkers such as microRNAs. The aim of our study was to evaluate the prognostic potential of microRNAs and their use as markers of disease recurrence. The quantitative estimation of CEA, CA19-9, and 22 selected microRNAs (TaqMan Advanced miRNA Assays) was performed in 85 paired (preoperative and postoperative) blood plasma samples of CRC patients and in samples taken during the follow-up period. We have revealed a statistically significant decrease in plasma levels for miR-20a, miR-23a, miR-210, and miR-223a (p = 0.0093, p = 0.0013, p = 0.0392, and p = 0.0214, respectively) after surgical removal of the tumor tissue. A statistically significant relation to prognosis (overall survival; OS) was recorded for preoperative plasma levels of miR-20a, miR-21, and miR-23a (p = 0.0236, p = 0.0316, and p =0.0271, respectively) in a subgroup of patients who underwent palliative surgery. The best discrimination between patients with favorable and unfavorable outcomes was achieved by a combination of CEA, CA19-9 with miR-21, miR-20a, and miR-23a (p < 0.0001). The use of these microRNAs for early disease recurrence detection was affected by a low specificity in comparison with CEA and CA19-9. CEA and CA19-9 had high specificity but low sensitivity. Our results show the benefit of combining currently used standard biomarkers and microRNAs for precise prognosis estimation.

Circulating miRNA Increases the Diagnostic Accuracy of Chromogranin A in Metastatic Pancreatic Neuroendocrine Tumors

“…However, the combination of CgA concentration and expression level of miRNAs in a regression model yielded higher AUC compared to those obtained using individual markers, demonstrating that our model was effective in distinguishing different groups in every comparison. Our results are in line with previous findings showing that in other cancer types, independently of individually being significantly different or not, combining more factors in a regression model increases the discriminatory value of biomarkers [ 61 , 62 ]. Therefore, the combination of a set of miRNAs together with CgA, even in the most challenging group (pNET patients with low CgA level or receiving PPI treatment) represents a promising diagnostic tool.…”

Function and mechanisms of microRNA‑20a in colorectal cancer (Review)

“…Furthermore, carcinoembryonic antigen (CEA) is a common tumor marker in gastrointestinal cancer, but its specificity and sensitivity are low. The combination of miR-20a with CEA and CA19-9 can improve the sensitivity and specificity of CEA, allowing patients to obtain the most accurate prognosis (127).…”

The Level of Preoperative Plasma KRAS Mutations and CEA Predict Survival of Patients Undergoing Surgery for Colorectal Cancer Liver Metastases

“…However, a mechanistic role for soluble CEA in tumor progression and metastasis remains to be established [ 32 ]. CEA is the biochemical gold standard for early detection of cancer recurrence, recommended by both the American Society of Clinical Oncology (ASCO) and the European Group on Tumor Markers (EGTM) [ 34 ]. This marker is also one of the most commonly used prognostic factors for CRC [ 35 ].…”