Prognostic microRNAs in upper tract urothelial carcinoma: multicenter and international validation study

Izquierdo, Laura; Montalbo, Ruth; Ingelmo-Torres, Mercedes; Mallofré, Carme; Ramírez‐Backhaus, M.; Rubio, José; Heijden, Antoine G. van der; Schaafsma, Ewout; López-Beltrán, Antonio; Blanca, Ana; Lawrentschuk, Nathan; Alcaraz, Antonio; Mengual, Lourdes

doi:10.18632/oncotarget.17884

Cited by 12 publications

(6 citation statements)

References 45 publications

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“…The pathogenesis and prognosis of many cancers has implicated the deregulation of miRNAs, which play vital roles in regulating the expression of coding genes involved in a wide range of biological processes [14, 15]. Therefore, several studies have investigated the clinical value of miRNAs for the prediction of cancer outcomes [9, 16, 17]. Koolivand et al observed that miR-155 might function as an oncomir in AML and can be a prognosis biomarker for AML [18], while Xu H et al have reported role for miR-135a in predicting poor prognosis in AML [19].…”

Section: Discussionmentioning

confidence: 99%

Selection of three miRNA signatures with prognostic value in non-M3 acute myeloid leukemia

Xue

Kang

et al. 2019

BMC Cancer

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Background MiRNAs that are potential biomarkers for predicting prognosis for acute myeloid leukemia (AML) have been identified. However, comprehensive analyses investigating the association between miRNA expression profiles and AML survival remain relatively deficient. Method In the present study, we performed multivariate Cox’s analysis and principal component analysis (PCA) using data from The Cancer Genome Atlas (TCGA) to identify potential molecular signatures for predicting non-M3 AML prognosis. Result We found that patients who were still living were significantly younger at diagnosis than those who had died ( P = 0.001). In addition, there was a marked difference in living status among different risk category groups ( P = 0.022). A multivariate Cox model suggested that three miRNAs were potential biomarkers of non-M3 AML prognosis, including miR-181a-2, miR-25 and miR-362. Subsequently, PCA analyses were conducted to comprehensively represent the expression levels of these three miRNAs in each patient with a PCA value. According to the log-rank test, AML outcome for patients with lower PCA values was significantly different from those with higher PCA values ( P < 0.001). Further bioinformatic analysis revealed the biological functions of the selected miRNAs. Conclusion We conducted a comprehensive analysis of TCGA non-M3 AML data, identifying three miRNAs that are significantly correlated with AML survival. PCA values for the identified miRNAs are valuable for predicting AML prognosis. Electronic supplementary material The online version of this article (10.1186/s12885-019-5315-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Selection of three miRNA signatures with prognostic value in non-M3 acute myeloid leukemia

Xue

Kang

et al. 2019

BMC Cancer

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“…Our group has prior experience in miRNA analysis from different types of urothelial cell carcinoma samples. On the one hand, we provided evidence that miRNAs can be used as prognostic biomarkers in UTUC in tissue samples [ 3 , 4 ]. On the other, we showed that miRNAs can be useful diagnostic and prognostic biomarkers for bladder cancer in urine samples [ 12 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of circulating microRNAs in upper tract urinary carcinoma

et al. 2018

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The identification of upper tract urinary carcinoma (UTUC) prognostic biomarkers is urgently needed to predict tumour progression. This study aimed to identify serum microRNAs (miRNAs) that may be useful as minimally invasive predictive biomarkers of tumour progression and survival in UTUC patients. To this end, 33 UTUC patients who underwent radical nephroureterectomy at the Hospital Clinic of Barcelona were prospectively included. Expression of 800 miRNAs was evaluated in serum samples from these patients using nCounter® miRNA Expression Assays. The study was divided into an initial discovery phase (n=12) and a validation phase (n=21). Cox regression analysis was used for survival analysis. The median follow-up (range) of the series was 42 months (9-100 months). In the discovery phase, 38 differentially expressed miRNAs were identified between progressing and non-progressing UTUC patients (p<0.05). Validation of these 38 miRNAs in an independent set of UTUC patients confirmed the differential expression in 18 of them (p<0.05). Cox Regression analysis showed miR-151b and pathological stage as significant prognostic factors for tumour progression (HR=0.33, p<0.001 and HR=2.62, p=0.006, respectively) and cancer specific survival (HR=0.25, p<0.001 and HR=3.98, p=0.003, respectively). Survival curves revealed that miR-151b is able to discriminate between two groups of UTUC patients with a highly significant different probability of tumour progression (p=0.006) and cancer specific survival (p=0.034). Although the data needs to be externally validated, miRNA analysis in serum appears to be a valuable prognostic tool in UTUC patients. Particularly, differential expression of miR-151b in serum may serve as a minimally invasive prognostic tool in UTUC.

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“…In UTUC, miRNAs that play a major role in tumor progression and cancer-specific survival were identified as regulators of gene expression, including oncogene and tumor suppressor genes. Signalling pathways modified by prognostic markers have been recognized as being involved in UTUC progression ( Izquierdo et al, 2017 ). The regulatory roles of miRNAs in cell growth, apoptosis, autophagy, and aging have also been implicated ( Sohn, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of potential genes in upper tract urothelial carcinoma using next-generation sequencing with bioinformatics and in vitro analyses

Lee

et al. 2021

PeerJ

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Background We aimed to identify prognostic biomarkers of upper tract urothelial carcinomas (UTUCs), including microRNAs (miRNAs) and genes which account for only 5% to 10% of all urothelial carcinomas (UCs). In Taiwan, this figure is markedly higher, where it can reach up to 30% of UC cases. Materials and Methods Using next-generation sequencing (NGS), we analyzed two pairs of renal pelvis tumors and adjacent normal urothelial tissues to screen miRNAs and messenger RNAs. By combining bioinformatics analysis from miRmap, Gene Expression Omnibus (GEO), and Oncomine and Ingenuity® Pathway Analysis databases, we identified candidate genes. To search for upstream miRNAs with exact target binding sites, we used miRmap, TargetScan, and miRDB to enforce evidence. Then, we clarified gene and protein expression through an in vitro study using western blot analysis and quantitative real-time reverse transcriptase-PCR. Results Interactions between selected target genes obtained using the NGS and miRmap methods were assessed through a Venn diagram analysis. Six potential genes, namely, PDE5A, RECK, ZEB2, NCALD, PLCXD3 and CYBRD1 showed significant differences. Further analysis of gene expression from the GEO dataset indicated lower expression of PDE5A, RECK, ZEB2, and CYBRD1 in bladder cancer tissue than in normal bladder mucosa, which indicated that PDE5A, RECK, ZEB2, and CYBRD1 may act as tumor suppressors in UTUC. In addition, we compared the expression of these genes in various UC cell lines (RT4, BFTC905, J82, T24, UMUC3, 5637, BFTC 909, UMUC14) and found decreased expression of PDE5A in muscle-invasive UC cells compared with the RT4 cell line. Furthermore, by using paired UTUC and normal tissues from 20 patients, lower PDE5A expression was also demonstrated in tumor specimens. Conclusions Our findings suggest these candidate genes may play some roles in UTUC progression. We propose that these markers may be potential targets clarified by in vitro and in vivo experiments. PDE5A also potentially presents tumor suppressor genes, as identified by comparing the expression between normal and tumor specimens.

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Prognostic microRNAs in upper tract urothelial carcinoma: multicenter and international validation study

Cited by 12 publications

References 45 publications

Selection of three miRNA signatures with prognostic value in non-M3 acute myeloid leukemia

Selection of three miRNA signatures with prognostic value in non-M3 acute myeloid leukemia

Prognostic value of circulating microRNAs in upper tract urinary carcinoma

Identification of potential genes in upper tract urothelial carcinoma using next-generation sequencing with bioinformatics and in vitro analyses

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