Two Microrna Signatures for Malignancy and Immune Infiltration Predict Overall Survival in Advanced Epithelial Ovarian Cancer

Korsunsky, Ilya; Parameswaran, Janaki; Shapira, Iuliana; Lovecchio, John L.; Menzin, Andrew; Whyte, Jill; Santos, L. dos; Liang, Sharon X.; Bhuiya, Tawfiqul; Keogh, Mary; Khalili, Houman; Pond, Cassandra; Liew, Anthony; Shih, Andrew; Gregersen, Peter K.; Lee, Annette T.

doi:10.1136/jim-2017-000457

Cited by 12 publications

(9 citation statements)

References 45 publications

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“…Given the oncogenic function of miR-328 in ovarian cancer, we sought to determine whether there is a relationship between the level of miR-328 expression and the prognosis in human patients with ovarian cancer. Korsunsky and colleagues have profiled miRNA expression in 19 EOC and 13 benign ovarian masses using TaqMan OpenArray (34). We reanalyzed these data (GSE81873) and found that the miR-328 level is higher in EOC than benign tissues (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of miR-328–3p Impairs Cancer Stem Cell Function and Prevents Metastasis in Ovarian Cancer

et al. 2019

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Cancer stem cells (CSC) play a central role in cancer metastasis and development of drug resistance. miRNA are important in regulating CSC properties and are considered potential therapeutic targets. Here we report that miR-328–3p (miR-328) is significantly upregulated in ovarian CSC. High expression of miR-328 maintained CSC properties by directly targeting DNA damage binding protein 2, which has been shown previously to inhibit ovarian CSC. Reduced activity of ERK signaling in ovarian CSC, mainly due to a low level of reactive oxygen species, contributed to the enhanced expression of miR-328 and maintenance of CSC. Inhibition of miR-328 in mouse orthotopic ovarian xenografts impeded tumor growth and prevented tumor metastasis. In summary, our findings provide a novel mechanism underlying maintenance of the CSC population in ovarian cancer and suggest that targeted inhibition of miR-328 could be exploited for the eradication of CSC and aversion of tumor metastasis in ovarian cancer. Significance: These findings present inhibition of miR-328 as a novel strategy for efficient elimination of CSC to prevent tumor metastasis and recurrence in patients with epithelial ovarian cancer.

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Section: Resultsmentioning

confidence: 99%

Inhibition of miR-328–3p Impairs Cancer Stem Cell Function and Prevents Metastasis in Ovarian Cancer

et al. 2019

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“…However, the traditional immunohistochemistry immunoscoring approach remains suboptimal because of lacking a consistent standard and limited number of biomarkers assessed simultaneously. 34 Recently, molecular profiling-based approaches and signatures have been used to infer immune infiltration, such as mRNAs, 31 microRNA 35 and DNA methylation. 36 lncRNA, a recently identified key players of genome regulatory network, has also been found to play critical roles in the development and activation of immune cells, and may, therefore, serve as a specific molecular marker for tumor-infiltrating immune cells.…”

Section: Discussionmentioning

confidence: 99%

Identification of tumor immune infiltration-associated lncRNAs for improving prognosis and immunotherapy response of patients with non-small cell lung cancer

Sun

Zhang

Bao

et al. 2020

J Immunother Cancer

223

195

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BackgroundIncreasing evidence has demonstrated the functional relevance of long non-coding RNAs (lncRNAs) to immunity regulation and the tumor microenvironment in non-small cell lung cancer (NSCLC). However, tumor immune infiltration-associated lncRNAs and their value in improving clinical outcomes and immunotherapy remain largely unexplored.MethodsWe developed a computational approach to identify an lncRNA signature (TILSig) as an indicator of immune cell infiltration in patients with NSCLC through integrative analysis for lncRNA, immune and clinical profiles of 115 immune cell lines, 187 NSCLC cell lines and 1533 patients with NSCLC. Then the influence of the TILSig on the prognosis and immunotherapy in NSCLC was comprehensively investigated.ResultsComputational immune and lncRNA profiling analysis identified an lncRNA signature (TILSig) consisting of seven lncRNAs associated with tumor immune infiltration. The TILSig significantly stratified patients into the immune-cold group and immune-hot group in both training and validation cohorts. These immune-hot patients exhibit significantly improved survival outcome and greater immune cell infiltration compared with immune-cold patients. Multivariate analysis revealed that the TILSig is an independent predictive factor after adjusting for other clinical factors. Further analysis accounting for TILSig and immune checkpoint gene revealed that the TILSig has a discriminatory power in patients with similar expression levels of immune checkpoint genes and significantly prolonged survival was observed for patients with low TILSig and low immune checkpoint gene expression implying a better response to immune checkpoint inhibitor (ICI) immunotherapy.ConclusionsOur finding demonstrated the importance and value of lncRNAs in evaluating the immune infiltrate of the tumor and highlighted the potential of lncRNA coupled with specific immune checkpoint factors as predictive biomarkers of ICI response to enable a more precise selection of patients.

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“…The presence of infiltrating cells may influence the tumour cells' HLA expression, as we previously described [40]. In a study involving epithelial ovarian cancer (another immune-privileged organ), miR-22 was similarly associated with the presence of an intra-tumoural immune infiltrate [54].…”

Section: Discussionmentioning

confidence: 77%

MiRNAs Correlate with HLA Expression in Uveal Melanoma: Both Up- and Downregulation Are Related to Monosomy 3

Souri

Wierenga

Kılıç

et al. 2021

Cancers

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MicroRNAs are known to play a role in the regulation of inflammation. As a high HLA Class I expression is associated with a bad prognosis in UM, we set out to determine whether any miRNAs were related to a high HLA Class I expression and inflammation. We also determined whether such miRNAs were related to the UM’s genetic status. The expression of 125 miRNAs was determined in 64 primary UM from Leiden. Similarly, the mRNA expression of HLA-A, HLA-B, TAP1, BAP1, and immune cell markers was obtained. Expression levels of 24 of the 125 miRNAs correlated with expression of at least three out of four HLA Class I probes. Four miRNAs showed a positive correlation with HLA expression and infiltration with leukocytes, 20 a negative pattern. In the first group, high miRNA levels correlated with chromosome 3 loss/reduced BAP1 mRNA expression, in the second group low miRNA levels. The positive associations between miRNA-22 and miRNA-155 with HLA Class I were confirmed in the TCGA study and Rotterdam cohort, and with TAP1 in the Rotterdam data set; the negative associations between miRNA-125b2 and miRNA-211 and HLA-A, TAP1, and CD4 were confirmed in the Rotterdam set. We demonstrate two patterns: miRNAs can either be related to a high or a low HLA Class I/TAP1 expression and the presence of infiltrating lymphocytes and macrophages. However, both patterns were associated with chromosome 3/BAP1 status, which suggests a role for BAP1 loss in the regulation of HLA expression and inflammation in UM through miRNAs.

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Two Microrna Signatures for Malignancy and Immune Infiltration Predict Overall Survival in Advanced Epithelial Ovarian Cancer

Cited by 12 publications

References 45 publications

Inhibition of miR-328–3p Impairs Cancer Stem Cell Function and Prevents Metastasis in Ovarian Cancer

Inhibition of miR-328–3p Impairs Cancer Stem Cell Function and Prevents Metastasis in Ovarian Cancer

Identification of tumor immune infiltration-associated lncRNAs for improving prognosis and immunotherapy response of patients with non-small cell lung cancer

MiRNAs Correlate with HLA Expression in Uveal Melanoma: Both Up- and Downregulation Are Related to Monosomy 3

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