Dataset Information

Differential expression of ?V?3 and ?V?6 integrins in prostate cancer progression.

ABSTRACT: Neuroendocrine prostate cancer (NEPrCa) arises de novo or after accumulation of genomic alterations in pre-existing adenocarcinoma tumors in response to androgen deprivation therapies. We have provided evidence that small extracellular vesicles released by PrCa cells and containing the ?V?3 integrin promote neuroendocrine differentiation of PrCa in vivo and in vitro. Here, we examined ?V?3 integrin expression in three murine models carrying a deletion of PTEN (SKO), PTEN and RB1 (DKO), or PTEN, RB1 and TRP53 (TKO) genes in the prostatic epithelium; of these three models, the DKO and TKO tumors develop NEPrCa with a gene signature comparable to those of human NEPrCa. Immunostaining analysis of SKO, DKO and TKO tumors shows that ?V?3 integrin expression is increased in DKO and TKO primary tumors and metastatic lesions, but absent in SKO primary tumors. On the other hand, SKO tumors show higher levels of a different ?V integrin, ?V?6, as compared to DKO and TKO tumors. These results are confirmed by RNA-sequencing analysis. Moreover, TRAMP mice, which carry NEPrCa and adenocarcinoma of the prostate, also have increased levels of ?V?3 in their NEPrCa primary tumors. In contrast, the ?V?6 integrin is only detectable in the adenocarcinoma areas. Finally, analysis of 42 LuCaP patient-derived xenografts and primary adenocarcinoma samples shows a positive correlation between ?V?3, but not ?V?6, and the neuronal marker synaptophysin; it also demonstrates that ?V?3 is absent in prostatic adenocarcinomas. In summary, we demonstrate that ?V?3 integrin is upregulated in NEPrCa primary and metastatic lesions; in contrast, the ?V?6 integrin is confined to adenocarcinoma of the prostate. Our findings suggest that the ?V?3 integrin, but not ?V?6, may promote a shift in lineage plasticity towards a NE phenotype and might serve as an informative biomarker for the early detection of NE differentiation in prostate cancer.

SUBMITTER: Quaglia F

PROVIDER: S-EPMC7822502 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Differential expression of αVβ3 and αVβ6 integrins in prostate cancer progression.

Quaglia Fabio F Krishn Shiv Ram SR Wang Yanqing Y Goodrich David W DW McCue Peter P Kossenkov Andrew V AV Mandigo Amy C AC Knudsen Karen E KE Weinreb Paul H PH Corey Eva E Kelly William K WK Languino Lucia R LR

PloS one 20210122 1

Neuroendocrine prostate cancer (NEPrCa) arises de novo or after accumulation of genomic alterations in pre-existing adenocarcinoma tumors in response to androgen deprivation therapies. We have provided evidence that small extracellular vesicles released by PrCa cells and containing the αVβ3 integrin promote neuroendocrine differentiation of PrCa in vivo and in vitro. Here, we examined αVβ3 integrin expression in three murine models carrying a deletion of PTEN (SKO), PTEN and RB1 (DKO), or PTEN, ...[more]

PMID: 33481853

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Project description:BACKGROUND: The identification of gene differential co-expression patterns between cancer stages is a newly developing method to reveal the underlying molecular mechanisms of carcinogenesis. Most researches of this subject lack an algorithm useful for performing a statistical significance assessment involving cancer progression. Lacking this specific algorithm is apparently absent in identifying precise gene pairs correlating to cancer progression. RESULTS: In this investigation we studied gene pair co-expression change by using a stochastic process model for approximating the underlying dynamic procedure of the co-expression change during cancer progression. Also, we presented a novel analytical method named 'Stochastic process model for Identifying differentially co-expressed Gene pair' (SIG method). This method has been applied to two well known prostate cancer data sets: hormone sensitive versus hormone resistant, and healthy versus cancerous. From these data sets, 428,582 gene pairs and 303,992 gene pairs were identified respectively. Afterwards, we used two different current statistical methods to the same data sets, which were developed to identify gene pair differential co-expression and did not consider cancer progression in algorithm. We then compared these results from three different perspectives: progression analysis, gene pair identification effectiveness analysis, and pathway enrichment analysis. Statistical methods were used to quantify the quality and performance of these different perspectives. They included: Re-identification Scale (RS) and Progression Score (PS) in progression analysis, True Positive Rate (TPR) in gene pair analysis, and Pathway Enrichment Score (PES) in pathway analysis. Our results show small values of RS and large values of PS, TPR, and PES; thus, suggesting that gene pairs identified by the SIG method are highly correlated with cancer progression, and highly enriched in disease-specific pathways. From this research, several gene interaction networks inferred could provide clues for the mechanism of prostate cancer progression. CONCLUSION: The SIG method reliably identifies cancer progression correlated gene pairs, and performs well both in gene pair ontology analysis and in pathway enrichment analysis. This method provides an effective means of understanding the molecular mechanism of carcinogenesis by appropriately tracking down the process of cancer progression.

Dataset Information

Differential expression of ?V?3 and ?V?6 integrins in prostate cancer progression.

Publications

Differential expression of αVβ3 and αVβ6 integrins in prostate cancer progression.

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