Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets

Abstract

Multiple studies suggested using different miRNAs as biomarkers for prognosis of hepatocellular carcinoma (HCC). We aimed to assemble a miRNA expression database from independent datasets to enable an independent validation of previously published prognostic biomarkers of HCC. A miRNA expression database was established by searching the TCGA (RNA-seq) and GEO (microarray) repositories to identify miRNA datasets with available expression and clinical data. A PubMed search was performed to identify prognostic miRNAs for HCC. We performed a uni- and multivariate Cox regression analysis to validate the prognostic significance of these miRNAs. The Limma R package was applied to compare the expression of miRNAs between tumor and normal tissues. We uncovered 214 publications containing 223 miRNAs identified as potential prognostic biomarkers for HCC. In the survival analysis, the expression levels of 55 and 84 miRNAs were significantly correlated with overall survival in RNA-seq and gene chip datasets, respectively. The most significant miRNAs were hsa-miR-149, hsa-miR-139, and hsa-miR-3677 in the RNA-seq and hsa-miR-146b-3p, hsa-miR-584, and hsa-miR-31 in the microarray dataset. Of the 223 miRNAs studied, the expression was significantly altered in 102 miRNAs in tumors compared to normal liver tissues. In summary, we set up an integrated miRNA expression database and validated prognostic miRNAs in HCC.

PHLPP2 as a novel metastatic and prognostic biomarker in non‐small cell lung cancer patients

“…The survival curves of OS (HR 0.508, 95% CI 0.327–0.790; P = 0.002) and DFS (HR 0.481, 95% CI 0.311–0.745; P = 0.001) are shown in Figure a. Furthermore, the Kaplan‐Meier plotter online tool was used to validate the effect of PHLPP2 on lung cancer survival ( n = 1926) . The results consistently show that patients with elevated levels of PHLPP2 expression had longer OS ( P = 0.00013) and post progression survival (PPS) ( P = 0.012) than those with low PHLPP2 expression levels (Fig b).…”

“…Furthermore, the Kaplan-Meier plotter online tool was used to validate the effect of PHLPP2 on lung cancer survival (n = 1926). 26 The results consistently show that patients with elevated levels of PHLPP2 expression had longer OS (P = 0.00013) and post progression survival (PPS) (P = 0.012) than those with low PHLPP2 expression levels (Fig 3b). Using the web-based tools in The Human Protein Atlas (https://www.proteinatlas.org) based on TCGA, low PHLPP2 expression predicts a poor prognosis in ADC ( Fig S2).…”

High RIG‐I expression in ovarian cancer associates with an immune‐escape signature and poor clinical outcome

“…21 The tool, termed Kaplan-Meier Plotter, 22 generates Kaplan-Meier survival plots using underlying TCGA data and supports automated selection of the best cutoff for two-group dichotomization. kmplot.com/ovar.…”

Role of regulatory miRNAs of the PI3K/AKT/mTOR signaling in the pathogenesis of hepatocellular carcinoma

“…A growing body of evidence suggests that miRNAs can be used as diagnostic biomarkers for several human malignancies including breast, lung, and gastric cancers (Bahrami et al, ; Komatsu, Kiuchi, Imamura, Ichikawa, & Otsuji, ; Yu, Guan, Cuk, Brenner, & Zhang, ). It has been reported that miRNAs can be used as potential diagnostic biomarkers in HCC (Nagy, Lánczky, Menyhárt, & Győrffy, ). For instance, three miRNAs including miR‐10b, miR‐106b, and miR‐181a were found to have considerable potential as diagnostic biomarkers for HCC (Lu et al, ).…”