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首頁(yè)> 外文期刊>Progress in Artificial Intelligence >Androgen Receptor and Its Splicing Variant 7 Expression in Peripheral Blood Mononuclear Cells and in Circulating Tumor Cells in Metastatic Castration-Resistant Prostate Cancer
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Androgen Receptor and Its Splicing Variant 7 Expression in Peripheral Blood Mononuclear Cells and in Circulating Tumor Cells in Metastatic Castration-Resistant Prostate Cancer

機(jī)譯：外周血單核細(xì)胞中雄激素受體及其剪接變體7表達(dá)及轉(zhuǎn)移閹割前列腺癌中的循環(huán)腫瘤細(xì)胞

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Androgen receptor (AR) signaling remains crucial in castration-resistant prostate cancer (CRPC). Since it is also essential in immune cells, we studied whether the expression of AR full-length (ARFL) and its splicing variant ARV7 in peripheral blood mononuclear cells (PBMC) predicts systemic treatment response in mCRPC in comparison with circulating-tumor cells (CTC). We measured ARFL and ARV7 mRNA in PBMC and CTC from patients prior to receiving abiraterone (AA), enzalutamide (E), or taxanes by a pre-amplification plus quantitative reverse-transcription PCR. They were also tested in LNCaP-ARV7-transfected and in 22RV1 docetaxel-resistant (22RV1DR) cells. We studied 171 PBMC from 136 patients and from 24 non-cancer controls, and 47 CTC from 22 patients. High PBMC ARV7 levels correlated with worse AA/E and better taxane response. In taxane-treated patients high PBMC ARFL also correlated with longer progression-free survival (PFS). High ARV7 and ARFL expression were independently associated with better biochemical-PFS. Conversely, high CTC ARV7 and ARFL correlated with shorter radiological-PFS and overall survival, respectively. High ARV7 in 22RV1DR and LNCaP-ARV7 cells correlated with taxane resistance. In conclusion, ARFL and ARV7 at PBMC or CTC have a different predictive role in the taxane response, suggesting a potential influence of the AR pathway from PBMC in such response modulation.
機(jī)譯：雄激素受體（AR）信號(hào)傳導(dǎo)在抗閹割前列腺癌（CRPC）中仍然至關(guān)重要。由于它在免疫細(xì)胞中也是必需的，我們研究了外周血單核細(xì)胞（PBMC）中AR全長(zhǎng)（ARFL）及其拼接變體ARV7的表達(dá)是否預(yù)測(cè)MCRPC中的全身治療響應(yīng)與循環(huán)腫瘤細(xì)胞（CTC ）。通過(guò)預(yù)擴(kuò)增加量加上定量逆轉(zhuǎn)錄PCR，在接受Abiraatorone（AA），烯甲醛胺（E）或紫杉烷之前，從PBMC和CTC中測(cè)量ARFL和ARV7 mRNA。它們也在LNCAP-ARV7轉(zhuǎn)染和22RV1抗性（22RV1DR）細(xì)胞中進(jìn)行測(cè)試。從136名患者和24例非癌癥對(duì)照中研究了171磅PBMC，以及22例患者的47例CTC。高PBMC ARV7水平與更差的AA / E和更好的紫杉烷反應(yīng)相關(guān)。在紫杉烷治療的患者中，高PBMC ARFR也與更長(zhǎng)的無(wú)進(jìn)展存活（PFS）相關(guān)。高ARV7和ARCL表達(dá)與更好的生物化學(xué)-PFs獨(dú)立相關(guān)。相反，高CTC ARV7和ARFL分別與較短的放射線(xiàn) - PFS和整體存活相關(guān)。 22RV1DR中的高ARV7和LNCAP-ARV7細(xì)胞與紫杉烷抗性相關(guān)?？傊赑BMC或CTC處的ARFL和ARV7在紫杉烷反應(yīng)中具有不同的預(yù)測(cè)作用，表明AR途徑在這種反應(yīng)調(diào)制中對(duì)疾病途徑的潛在影響。

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