Peripherical Blood hsa-miR-335-5p Quantification as a Prognostic, but Not Diagnostic, Marker of Gastric Cancer

Abstract

Gastric cancer (GC) is a leading cause of death, and this pathology often receives a diagnosis in an advanced stage. The development of a less invasive and cost-effective test for detection is essential for decreasing the mortality rate and increasing the life expectancy of GC patients. We evaluated the potential targeting of CD54/ICAM1, a marker of gastric cancer stem cells, with miRNAs to detect GC in blood samples. The analyses included 79 blood samples, 38 from GC patients and 41 from healthy donors, who attended INCan, México City. The total RNA was obtained from the blood plasma, and RT-PCR and qPCR were performed to obtain the relative expression of each miRNA. Hsa-miR-335-5p was detected in the plasma of GC patients and healthy donors at the same levels. The ROC curve analyses indicated that this miRNA was not a candidate for the molecular diagnosis of GC. We did not observe a correlation between the expression of hsa-miR-335-5p and clinical variables; however, the Kaplan-Meier analyses indicated that, in patients who survived more than 12 months, a lower expression of hsa-miR-335-5p was correlated with a better prognosis. It would be convenient to evaluate a larger panel of miRNAs, including miRNAs expressed in a limited number of cell types or with a low number targets, to obtain more specific candidates for developing a robust test for the diagnosis/prognosis of GC.

Keywords: GC molecular markers; GC prognosis; gastric cancer; hsa-miR-335-5p; miRNA.

Figure 1

The relative expression of miR-335-5p/miR-16 in the blood plasma of GC patients and healthy donors did not change. The dotted box shows that the median relative expression of hsa-miR-335-5p/hsa-miR-16-5p in 38 GC patients was −0.092 (−0.432 +0.230); the gray box shows that the median relative expression of hsa-miR-335-5p/hsa-miR-16-5p in 41 healthy volunteers was 0.135 (−0.339, +0.684). The Mann–Whitney U test was used.

Figure 2

The overall survival rate of GC patients according to their hsa-miR-335-5p expression. The Kaplan–Meier gross analyses did not show an association between the hsa-miR-335-5p expression level and the overall survival (p = 0.271). After adjusting based on survival beyond 12 months, a decreased expression of hsa-miR-335-5p was associated with a good prognosis (p = 0.031).

Figure 3

The relative expression of hsa-miR335-5p had no diagnostic value for patients with GC. The ROC curve showed a sensibility, specificity, and AUC of 37%, 44%, and 0.39 (blue line in the plot).