Abstract
BackgroundNovel non-invasive biomarkers for gastric cancer (GC) are needed, because the present diagnostic methods for GC are either invasive or insensitive and non-specific in clinic. The presence of stable circulating microRNAs (miRNAs) in plasma suggested a promising role as GC biomarkers.MethodsBased on the quantitative droplet digital PCR (ddPCR), four miRNAs (miR-21, miR-93, miR-106a and miR-106b) related to the presence of GC were identified in plasma from a training cohort of 147 participants and a validation cohort of 28 participants.ResultsAll circulating miRNA levels were significantly higher in the plasma of GC patients compared to healthy controls (P < 0.05). Through a combination of four miRNAs by logistic regression model, receiver operating characteristic (ROC) analyses yielded the highest AUC value of 0.887 in discriminating GC patients from healthy volunteers. Furthermore, miR-21, miR-93 and miR-106b levels were significantly related to an advanced TNM stage in GC patients. ROC analyses of the combined miRNA panel also showed the highest AUC value of 0.809 in discriminating GC patients with TNM stage I and II from stage III and IV. Through combining four miRNAs and clinical parameters, a classical random forest model was established in the training stage. In the validation cohort, it correctly discriminated 23 out of 28 samples in the blinded phase (false rate, 17.8%).ConclusionsUsing the ddPCR technique, circulating miR-21, miR-93, miR-106a and miR-106b could be used as diagnostic plasma biomarkers in gastric cancer patients.
Highlights
Novel non-invasive biomarkers for gastric cancer (GC) are needed, because the present diagnostic methods for GC are either invasive or insensitive and non-specific in clinic
All four miRNAs including miR-21, miR-93, miR-106a and miR-106b levels were significantly lower in healthy controls than GC patients with TNM stage I (p = 0.0021, p = 0.0084, p = 0.0116 and p = 0.0168 respectively) (Fig. 1a), as well as TNM stage II, III and IV (Table 2)
GC patients with different TNM stage were combined as one group, the area under the curve (AUC) values of miR-21, miR-93, miR-106a and miR-106b were 0.811 (95% confidence interval [CI], 0.739–0.884), 0.751, 0.731 and 0.77, respectively (Fig. 1b)
Summary
Novel non-invasive biomarkers for gastric cancer (GC) are needed, because the present diagnostic methods for GC are either invasive or insensitive and non-specific in clinic. The presence of stable circulating microRNAs (miRNAs) in plasma suggested a promising role as GC biomarkers. Gastric cancer is second most common cancer in terms of incidence and mortality in China, according to the most recent cancer statistics [1]. With the improvement of surgical technique, radiotherapy and chemotherapy in recent years, patients in the early stage of GC had a significant increased 5-year survival rate, but the prognosis for advanced GC remains poor [2, 3]. MicroRNAs (miRNAs) are small noncoding RNAs, about 22–24 bases long, that inhibit their target mRNAs translation by inducing mRNA degradation or translational repression [5, 6].
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