Micro<scp>RNA</scp>‐17 as a promising diagnostic biomarker of gastric cancer: An investigation combining TCGA, GEO, meta‐analysis, and bioinformatics

Hu, Gaofeng; Lv, Qun; Yan, Jiaxiu; Chen, Lijun; Du, Juan; Zhao, Ke; Xu, Wei

doi:10.1002/2211-5463.12496

Cited by 10 publications

(6 citation statements)

References 47 publications

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“…Currently, multiple miRNAs have been investigated as candidate GC biomarker. Studies found that miR-17-5p was upregulated in tissue samples of GC patients, while no consensus has been made about its expression in the peripheral blood 28–30. We found that the upregulated miR-17-5p in plasma was superior to other miRNAs in GC detection.…”

Section: Discussionmentioning

confidence: 52%

Cell-free miR-17-5p as a diagnostic biomarker for gastric cancer inhibits dendritic cell maturation

Cui¹,

Xie²,

Qi³

et al. 2019

OTT

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Purpose Gastric cancer (GC) patients display aberrant miRNA expression and defective dendritic cell function. However, the role of cancer cell-derived oncomiR in GC detection and dendritic cell (DC) maturation remains largely elusive. Methods Candidate miRNAs were selected by deep sequencing (8 GC plasma samples vs 8 control plasma samples; 8 GC tissues vs 8 adjacent normal gastric tissues) and confirmed by PCR with 164 plasma samples and 72 formalin-fixed paraffin-embedded GC tissue samples. Their diagnostic performance was evaluated by receiver operating characteristic curve. Cy3 fluorescence signals in DCs, exposed to conditioned medium obtained from BGC-823 cells pre-transfected with Cy3-miR-17-5p, were determined by flow cytometry and visualized by confocal microscopy. Functional and phenotypical alterations of DCs were assayed when DCs were transfected with miR-17-5p in vitro. Results Deep sequencing and RT-PCR confirmed that five shared miRNAs were upregulated in plasma and tissue samples of GC patients. Cell-free miR-17-5p was superior to others in GC detection with an area under the curve of 0.82, and correlated with lymphatic metastasis and poor overall survival. GC cell-shuttled miR-17-5p can be delivered to immature DCs, and they significantly inhibited LPS-stimulated phenotypic maturation by diminishing the expression of maturation markers (MHC II, CD80 and CD86 molecules). In line with those alterations in the phenotypic markers, functional experiments demonstrated that miR-17-5p triggered an inhibitory effect on DCs endocytic activity and decreased tumor necrosis factor-α and IL-12 secretion, while enhancing IL-10 production. Mixed lymphocyte reaction showed that miR-17-5p inhibited the T cell stimulating effect of DCs and favored regulatory T cells expansion. Conclusion GC cell-derived miR-17-5p is a potential biomarker for GC detection. Taken up by DCs, miR-17-5p weakened antitumor immune responses via inhibiting the maturation of dendritic cells.

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Section: Discussionmentioning

confidence: 52%

Cell-free miR-17-5p as a diagnostic biomarker for gastric cancer inhibits dendritic cell maturation

Cui¹,

Xie²,

Qi³

et al. 2019

OTT

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“…Besides, we also found a close co-expression relationship between 3 miRNAs and genes, including hsa-miR-17, hsa-miR-23c, and hsa-miR-326. Among them, hsa-miR-17 was considered as a promising diagnostic biomarker of gastric cancer [37] and colorectal cancer [38], and hsa-miR-23c was involved in the pathogenesis of non-small cell lung cancer [39]. Furthermore, only hsa-miR-326 and its co-expressed gene ELFN2 was significantly associated with the survival time of EC patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Prognostic-Related miRNA-mRNA Pairs in the Progression of Endometrial Carcinoma

Dong

Zhang

et al. 2022

Gynecol Obstet Invest

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Objectives: Endometrial carcinoma (EC) is one of the leading causes of death from gynecological cancer due to the high recurrence rate. However, the molecular mechanisms of EC progression are not well understood. This study aimed to identify critical genes and miRNAs associated with the progression and prognosis of EC and find the potential mRNA-miRNA regulatory relationship. Design: The mRNA and miRNA data were downloaded from The Cancer Genome Atlas (TCGA) database. Next, differentially expressed genes (DEGs) were identified. Subsequently, prognosis-related genes and miRNAs were identified, followed by co-expression analysis of these mRNAs and miRNAs. Materials, Setting, and Methods: Samples in the mRNA microarray were divided into normal (n = 35), early stage (n = 385), and advanced stage (n = 153). Next, DEGs in normal versus early stage and early stage versus advanced stage were, respectively, identified, followed by Venn analysis to screen overlapping DEGs in 2 comparison groups. Based on the expression level of these DEGs, univariate Cox regression analysis and Kaplan-Meier method were performed to obtain prognosis-related genes. Moreover, genes-related miRNAs were predicted, and miRNA-mRNA co-expressed pairs were identified. Then, survival analysis of co-expressed miRNA was performed. Finally, co-expressed genes of key genes were identified, and then functional enrichment analysis was conducted. Results: After integrating analysis, 326 overlapping (309 upregulated and 17 downregulated) DEGs were obtained. Univariate Cox regression analysis showed that 44 mRNAs and 8 miRNAs were associated with the prognosis of EC. Combined with the co-expressed analysis, only one prognosis-related hsa-miR-326/ELFN2 axis was obtained. In addition, functional enrichment analysis showed that co-expressed genes of ELFN2 were mainly involved in the PI3K-Akt signaling pathway. Limitations: These findings were obtained via bioinformatics analysis, and thus further experimental studies are urgently demanded to validate our results. Conclusions: One key miRNA-mRNA regulatory pair (hsa-miR-326-ELFN2) was screened. This study provided a bioinformatics basis for the molecular mechanism of EC progression and might contribute to the identification of novel therapeutic targets.

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“…A cut-off value of 7.075 is applied for miR-421 to detect GC [75]. Similarly, several oncogenic proliferation-triggering miRNA such as miR-543 [76] targeting Sirtuin 1 (SIRT1), miR-106a targeting tissue inhibitor of metalloproteinases 2 (TIMP2) [77], or miR-17 which targets a number of genes involving in tumorigenesis, disease progression, invasion, and metastasis of GC [78,79] have been suggested as candidate markers for GC diagnosis.…”

Section: Diagnostic Potential Of Ctc In Gcmentioning

confidence: 99%

Emerging Role of Circulating Tumor Cells in Gastric Cancer

Huong

Gurshaney

Bình

et al. 2020

Cancers

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With over 1 million incidence cases and more than 780,000 deaths in 2018, gastric cancer (GC) was ranked as the 5th most common cancer and the 3rd leading cause of cancer deaths worldwide. Though several biomarkers, including carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), and cancer antigen 72-4 (CA72-4), have been identified, their diagnostic accuracies were modest. Circulating tumor cells (CTCs), cells derived from tumors and present in body fluids, have recently emerged as promising biomarkers, diagnostically and prognostically, of cancers, including GC. In this review, we present the landscape of CTCs from migration, to the presence in circulation, biologic properties, and morphologic heterogeneities. We evaluated clinical implications of CTCs in GC patients, including diagnosis, prognosis, and therapeutic management, as well as their application in immunotherapy. On the one hand, major challenges in using CTCs in GC were analyzed, from the differences of cut-off values of CTC positivity, to techniques used for sampling, storage conditions, and CTC molecular markers, as well as the unavailability of relevant enrichment and detection techniques. On the other hand, we discussed future perspectives of using CTCs in GC management and research, including the use of circulating tumor microembolies; of CTC checkpoint blockade in immunotherapy; and of organoid models. Despite the fact that there are remaining challenges in techniques, CTCs have potential as novel biomarkers and/or a non-invasive method for diagnostics, prognostics, and treatment monitoring of GC, particularly in the era of precision medicine.

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MicroRNA‐17 as a promising diagnostic biomarker of gastric cancer: An investigation combining TCGA, GEO, meta‐analysis, and bioinformatics

Cited by 10 publications

References 47 publications

<p>Cell-free miR-17-5p as a diagnostic biomarker for gastric cancer inhibits dendritic cell maturation</p>

<p>Cell-free miR-17-5p as a diagnostic biomarker for gastric cancer inhibits dendritic cell maturation</p>

Identification of Key Prognostic-Related miRNA-mRNA Pairs in the Progression of Endometrial Carcinoma

Emerging Role of Circulating Tumor Cells in Gastric Cancer

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