Transcriptional Profile Associated with Clinical Outcomes in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation and Docetaxel

Metastatic prostate cancer; Chemotherapy; Hormonal therapyCáncer de próstata metastásico; Quimioterapia; Terapia hormonalCàncer de pròstata metastàtic; Quimioteràpia; Teràpia hormonalBackground: Androgen deprivation therapy (ADT) and docetaxel (DX) combination is a standard therapy for metastatic hormone-sensitive prostate cancer (mHSPC) patients. (2) Methods: We investigate if tumor transcriptomic analysis predicts mHSPC evolution in a multicenter retrospective biomarker study. A customized panel of 184 genes was tested in mRNA from tumor samples by the nCounter platform in 125 mHSPC patients treated with ADT+DX. Gene expression was correlated with castration-resistant prostate cancer-free survival (CRPC-FS) and overall survival (OS). (3) Results: High expression of androgen receptor (AR) signature was independently associated with longer CRPC-FS (hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.3-0.9; p = 0.015), high expression of estrogen receptor (ESR) signature with longer CRPC-FS (HR 0.6, 95% CI 0.4-0.9; p = 0.019) and OS (HR 0.5, 95% CI 0.2-0.9, p = 0.024), and lower expression of tumor suppressor genes (TSG) (RB1, PTEN and TP53) with shorter OS (HR 2, 95% CI 1-3.8; p = 0.044). ARV7 expression was independently associated with shorter CRPC-FS (HR 1.5, 95% CI 1.1-2.1, p = 0.008) and OS (HR 1.8, 95% CI 1.2-2.6, p = 0.004), high ESR2 was associated with longer OS (HR 0.5, 95% CI 0.2-1, p = 0.048) and low expression of RB1 was independently associated with shorter OS (HR 1.9, 95% CI 1.1-3.2, p = 0.014). (4) Conclusions: AR, ESR, and TSG expression signatures, as well as ARV7, RB1, and ESR2 expression, have a prognostic value in mHSPC patients treated with ADT+DX

A methodology to quantify the differences between alternative methods of heart rate variability measurement

This work proposes a systematic procedure to report the differences between heart rate variability time series obtained from alternative measurements reporting the spread and mean of the differences as well as the agreement between measuring procedures and quantifying how stationary, random and normal the differences between alternative measurements are. A description of the complete automatic procedure to obtain a differences time series (DTS) from two alternative methods, a proposal of a battery of statistical tests, and a set of statistical indicators to better describe the differences in RR interval estimation are also provided. Results show that the spread and agreement depend on the choice of alternative measurements and that the DTS cannot be considered generally as a white or as a normally distributed process. Nevertheless, in controlled measurements the DTS can be considered as a stationary process.Peer ReviewedPostprint (published version

Single-Cell Multiomics Analysis of Myelodysplastic Syndromes and Clinical Response to Hypomethylating Therapy

Altres ajuts: Cellex Foundation, CEL007; Asociación Española Contra el Cáncer, AC18/000002Alterations in epigenetic marks, such as DNA methylation, represent a hallmark of cancer that has been successfully exploited for therapy in myeloid malignancies. Hypomethylating agents (HMAs), such as azacitidine (AZA), have become standard-of-care therapy to treat myelodysplastic syndromes (MDS), myeloid neoplasms that can evolve into acute myeloid leukemia (AML). However, our capacity to identify who will respond to HMAs, and the duration of response, remains limited. To shed light on this question, we have leveraged the unprecedented analytical power of single-cell technologies to simultaneously map the genome and immunoproteome of MDS samples throughout clinical evolution. We were able to chart the architecture and evolution of molecular clones in precious paired bone marrow MDS samples at diagnosis and post-treatment to show that a combined imbalance of specific cell lineages with diverse mutational profiles is associated with the clinical response of MDS patients to hypomethylating therapy

A methodology to quantify the differences between alternative methods of heart rate variability measurement

This work proposes a systematic procedure to report the differences between heart rate variability time series obtained from alternative measurements reporting the spread and mean of the differences as well as the agreement between measuring procedures and quantifying how stationary, random and normal the differences between alternative measurements are. A description of the complete automatic procedure to obtain a differences time series (DTS) from two alternative methods, a proposal of a battery of statistical tests, and a set of statistical indicators to better describe the differences in RR interval estimation are also provided. Results show that the spread and agreement depend on the choice of alternative measurements and that the DTS cannot be considered generally as a white or as a normally distributed process. Nevertheless, in controlled measurements the DTS can be considered as a stationary process.Peer Reviewe

Transcriptional profile associated with clinical outcomes in metastatic hormone-sensitive prostate cancer treated with androgen deprivation and docetaxel

Background: androgen deprivation therapy (ADT) and docetaxel (DX) combination is a standard therapy for metastatic hormone-sensitive prostate cancer (mHSPC) patients. (2) Methods: We investigate if tumor transcriptomic analysis predicts mHSPC evolution in a multicenter retrospective biomarker study. A customized panel of 184 genes was tested in mRNA from tumor samples by the nCounter platform in 125 mHSPC patients treated with ADT+DX. Gene expression was correlated with castration-resistant prostate cancer-free survival (CRPC-FS) and overall survival (OS). (3) Results: High expression of androgen receptor (AR) signature was independently associated with longer CRPC-FS (hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.3-0.9; p = 0.015), high expression of estrogen receptor (ESR) signature with longer CRPC-FS (HR 0.6, 95% CI 0.4-0.9; p = 0.019) and OS (HR 0.5, 95% CI 0.2-0.9, p = 0.024), and lower expression of tumor suppressor genes (TSG) (RB1, PTEN and TP53) with shorter OS (HR 2, 95% CI 1-3.8; p = 0.044). ARV7 expression was independently associated with shorter CRPC-FS (HR 1.5, 95% CI 1.1-2.1, p = 0.008) and OS (HR 1.8, 95% CI 1.2-2.6, p = 0.004), high ESR2 was associated with longer OS (HR 0.5, 95% CI 0.2-1, p = 0.048) and low expression of RB1 was independently associated with shorter OS (HR 1.9, 95% CI 1.1-3.2, p = 0.014). (4) Conclusions: AR, ESR, and TSG expression signatures, as well as ARV7, RB1, and ESR2 expression, have a prognostic value in mHSPC patients treated with ADT+DX