The correlation of circulating pro‐angiogenic miRNAs’ expressions with disease risk, clinicopathological features, and survival profiles in gastric cancer

Abstract

This study aimed to explore the correlation of circulating pro‐angiogenic miRNAs’ expressions with risk, clinicopathological features, and survival profiles in gastric cancer (GC). Three hundred and thirty‐three GC patients underwent radical resection and 117 health controls (HCs) were recruited for this study. Plasma samples were obtained from GC patients before the operation and from HCs after enrollment. Fourteen pro‐angiogenic miRNAs were asseassed by quantitative polymerase chain reaction (qPCR). Disease‐free survival (DFS) and overall survival (OS) of GC patients were calculated and the median follow‐up duration was 36.0 months. Seven out of 14 pro‐angiogenic miRNAs including let‐7f, miR‐17‐5p, miR‐18a, miR‐19b‐1, miR‐20a, miR‐210, and miR‐296 were observed to be elevated in GC patients compared with HCs. MiR‐18a, miR‐20a, and miR‐210 disclosed good predictive values of GC risk. Six pro‐angiogenic miRNAs including miR‐17‐5p, miR‐92a, miR‐210, miR‐20a, miR‐18a, and miR‐296 expressions were positively while 1 pro‐angiogenic miRNA (miR‐130a) was negatively correlated with tumor malignancy degree in GC patients. K‐M curve disclosed that 5 pro‐angiogenic miRNAs including miR‐17‐5p, miR‐18a, miR‐20a, miR‐92a, and miR‐210 correlated with worse DFS, while 4 pro‐angiogenic miRNAs including miR‐17‐5p, miR‐18a, miR‐20a, and miR‐210 associated with shorter OS. Further multivariate Cox's analysis revealed that miR‐17‐5p, miR‐18a, miR‐20a, and miR‐210 were independent predictive factors for unfavorable DFS and OS. In conclusion, circulating pro‐angiogenic miRNAs could serve as novel noninvasive biomarkers for disease risk and malignancy degree, and miR‐17‐5p, miR‐18a, miR‐20a, and miR‐210 are independent factors predicting poor prognosis in GC patients.

The Efficacy of miR-20a as a Diagnostic and Prognostic Biomarker for Colorectal Cancer: A Systematic Review and Meta-Analysis

“…The oncogene MYC induces the miR-17 family, which in turn dysregulates cell cycle progression, apoptosis, and tumor invasion via interactions with PTEN [25], E2F genes [26], and the transforming growth factor beta (TGF-β) pathway [27]. miR-20a has been shown to be upregulated across both solid and hematopoietic cancers [28] and has even been suggested as a diagnostic serum biomarker for gastric [29], nasopharyngeal [30], and prostate cancer [31]. However, miR-20a has been particularly noted for its regulatory role in CRC by upregulating the TGF-β signaling cascade.…”

Investigation of MiR-92a as a Prognostic Indicator in Cancer Patients: a Meta-Analysis

“…Most studies have explored that a poor prognosis of cancer patients comes with an upregulated expression of miR-92a in tumor tissues or blood. There are a number of studies reporting that patients with a high expression level of miR-92a experience a low survival rates or quick tumor progression and metastasis in colorectal cancer20-23, non-small cell lung cancer24, 25, osteosarcoma26, 27, hepatocellular carcinoma28, 29, gastric cancer30-32, esophageal squamous cell carcinoma33, multiple myeloma34, non-muscle invasive bladder cancers35 and nasopharyngeal carcinoma36. Nevertheless, some emerging studies have identified that an increased miR-92a level was closely linked to a favorable survival: Nilsson et al37 pointed out that upregulation of miR-92a was associated with decreased tumor macrophage infiltration and better outcomes in breast cancer.…”

Prognostic values of microRNA-130 family expression in patients with cancer: a meta-analysis and database test

“…Thirteen articles were further removed because no survival analysis results were reported and insufficient survival data were available to recalculate HR and 95% CI. Finally, 24 eligible articles (27 studies) [11, 14–18, 21–26, 30, 31, 44–53] including 12 articles [11, 14–18, 21, 44–48] for miRNA-130a and 12 articles (15 studies) [22–26, 30, 31, 49–53] for miRNA-130b were included in this meta-analysis. Three articles [23, 49, 52] included two cohort studies from different populations (Table 1).…”

“…The potential mechanisms may involved down-regulation of tumor suppressor gene, phosphatase and tensin homolog ( PTEN ) in osteosarcoma and breast cancer [11, 12], runt-related transcription factor 3 ( RUNX - 3 ) and collapsing-response mediator protein type 4 ( CRMP4 ) in gastric cancer [10, 17], peroxisome proliferator-activated receptor gamma ( PPARG ) in chorangiocarcinoma [16] and enhanced mammalian target of rapamycin (mTOR) signaling pathway in ovarian cancer [13]. However, a retrospective analysis showed that miRNA-130a had no significant effect on the prognosis of gastric cancer [18]. Moreover, miRNA-130a, acted like a tumor suppressor, has been reported to inhibit the androgen receptor (AR) and mitogen activated protein kinase (MAPK) pathways and target FOS-like antigen 1 ( FOSL1 ) in prostate cancer [19], and triple-negative breast cancer [20], respectively.…”