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Cysteine- rich secretory protein 3 (CRISP3), ERG and PTEN define a molecular subtype of prostate cancer with implication to patients' prognosis.

ABSTRACT: Cysteine- rich secretory protein 3 (CRISP3) prognostic significance in prostate cancer (PCA) has generated mixed result. Herein, we investigated and independently validated CRISP3 expression in relation to ERG and PTEN genomic aberrations and clinical outcome. CRISP3 protein expression was examined by immunohistochemistry using a cohort of patients with localized PCA (n?=?215) and castration resistant PCA (CRPC) (n?=?46). The Memorial Sloan Kettering (MSKCC) and Swedish cohorts were used for prognostic validation. Results showed, CRISP3 protein intensity to be significantly associated with neoplastic epithelium, being highest in CRPC vs. benign prostate tissue (p?

SUBMITTER: Al Bashir S

PROVIDER: S-EPMC3975646 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Cysteine- rich secretory protein 3 (CRISP3), ERG and PTEN define a molecular subtype of prostate cancer with implication to patients' prognosis.

Al Bashir Samir S Alshalalfa Mohammed M Hegazy Samar A SA Dolph Michael M Donnelly Bryan B Bismar Tarek A TA

Journal of hematology & oncology 20140307

Cysteine- rich secretory protein 3 (CRISP3) prognostic significance in prostate cancer (PCA) has generated mixed result. Herein, we investigated and independently validated CRISP3 expression in relation to ERG and PTEN genomic aberrations and clinical outcome. CRISP3 protein expression was examined by immunohistochemistry using a cohort of patients with localized PCA (n = 215) and castration resistant PCA (CRPC) (n = 46). The Memorial Sloan Kettering (MSKCC) and Swedish cohorts were used for pro ...[more]

PMID: 24606912

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Project description:BACKGROUND:Cysteine-RIch Secretory Proteins (CRISP) are expressed in the reproductive tract of mammalian males and are involved in fertilization and related processes. Due to their important role in sperm performance and sperm-egg interaction, these genes are likely to be exposed to strong selective pressures, including postcopulatory sexual selection and/or male-female coevolution. We here perform a comparative evolutionary analysis of Crisp genes in mammals. Currently, the nomenclature of CRISP genes is confusing, as a consequence of discrepancies between assignments of orthologs, particularly due to numbering of CRISP genes. This may generate problems when performing comparative evolutionary analyses of mammalian clades and species. To avoid such problems, we first carried out a study of possible orthologous relationships and putative origins of the known CRISP gene sequences. Furthermore, and with the aim to facilitate analyses, we here propose a different nomenclature for CRISP genes (EVAC1-4, "EVolutionarily-analyzed CRISP") to be used in an evolutionary context. RESULTS:We found differing selective pressures among Crisp genes. CRISP1/4 (EVAC1) and CRISP2 (EVAC2) orthologs are found across eutherian mammals and seem to be conserved in general, but show signs of positive selection in primate CRISP1/4 (EVAC1). Rodent Crisp1 (Evac3a) seems to evolve under a comparatively more relaxed constraint with positive selection on codon sites. Finally, murine Crisp3 (Evac4), which appears to be specific to the genus Mus, shows signs of possible positive selection. We further provide evidence for sexual selection on the sequence of one of these genes (Crisp1/4) that, unlike others, is thought to be exclusively expressed in male reproductive tissues. CONCLUSIONS:We found differing selective pressures among CRISP genes and sexual selection as a contributing factor in CRISP1/4 gene sequence evolution. Our evolutionary analysis of this unique set of genes contributes to a better understanding of Crisp function in particular and the influence of sexual selection on reproductive mechanisms in general.

Dataset Information

Cysteine- rich secretory protein 3 (CRISP3), ERG and PTEN define a molecular subtype of prostate cancer with implication to patients' prognosis.

Publications

Cysteine- rich secretory protein 3 (CRISP3), ERG and PTEN define a molecular subtype of prostate cancer with implication to patients' prognosis.

Similar Datasets

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