Prostate cancer biomarker

PURPOSE: Prostate cancer (CaP) patients with low-grade tumors are enrolled in active surveillance (AS) programs and monitored with digital rectal exams (DREs), prostate-specific antigen (PSA) tests, and periodic invasive biopsies. Patients are "reclassified" with higher-risk disease if they show signs of disease progression. However, AS patients who will reclassify cannot be easily identified upfront and suffer morbidities associated with biopsy. Biomarkers derived from noninvasively obtained specimens such as serum or urine samples are promising alternatives to monitor patients with clinically insignificant cancer...

Prostate cancer (PCa) is the most prevalent malignancy and the second leading cause of cancer-related deaths in the male population in western countries, and we explored the association between exonuclease 1 (EXO1) expression and clinical progression, metastasis (Met), and survival prognosis of PCa. EXO1 expression of high/low-metastatic patient-derived xenografts model was investigated and clinical correlation and prognosis outcomes were validated. EXO1 in high-metastatic models was significantly increased compared with low-metastatic lines...

Androgen deprivation therapy (ADT) has been the standard of care for the last 75 years in metastatic hormone sensitive prostate cancer (PCa). However, this approach is rarely curative. Recent clinical trials have demonstrated that ADT combined with other agents, notably docetaxel and abiraterone, lead to improved survival. The mechanisms surrounding this improved cancer outcomes are incompletely defined. The response of cancer cells to ADT includes apoptosis and cell death, but a significant fraction remains viable...

Androgen deprivation therapy for prostate cancer (PCa) benefits patients with early disease, but becomes ineffective as PCa progresses to a castration-resistant state (CRPC). Initially CRPC remains dependent on androgen receptor (AR) signaling, often through increased expression of full-length AR (ARfl) or expression of dominantly active splice variants such as ARv7. We show in ARv7-dependent CRPC models that ARv7 binds together with ARfl to repress transcription of a set of growth-suppressive genes. Expression of the ARv7-repressed targets and ARv7 protein expression are negatively correlated and predicts for outcome in PCa patients...

Plasma androgen receptor (AR) gain identifies metastatic castration-resistant prostate cancer (mCRPC) patients with worse outcome on abiraterone/enzalutamide, but its relevance in the context of taxane chemotherapy is unknown. We aimed to evaluate whether docetaxel is active regardless of plasma AR and to perform an exploratory analysis to compare docetaxel with abiraterone/enzalutamide. This multi-institutional study was a pooled analysis of AR status, determined by droplet digital polymerase chain reaction, on pretreatment plasma samples...

CONTEXT: Recent studies focused on the molecular characterization of metastatic prostate cancer have identified genomic subsets and emerging resistance patterns. Detection of these alterations in patients has potential implications for therapy selection and prognostication. OBJECTIVE: The primary objective is to review the current landscape of clinical and molecular biomarkers in advanced prostate cancer and understand how they may reflect underlying tumor biology...

PURPOSE: Contemporary treatment for metastatic hormone sensitive prostate cancer (mHSPC) includes androgen deprivation therapy (ADT) plus abiraterone or docetaxel. While these intensified regimens have improved efficacy, they are also associated with increased cost and toxicities. Not all men with mHSPC may be candidates for these intensified regimens, yet there are no clinical models or biomarkers used to optimize treatment selection. Herein, we hypothesized that longer time from prior definitive therapy (DT), either radical prostatectomy, definitive radiotherapy, or both, to onset of metastatic disease is associated with improved survival outcomes in men with newly diagnosed mHSPC...

The relationship between cancer and inflammation is one of the most important fields for both clinical and translational research. Despite numerous studies reported interesting and solid data about the prognostic value of the presence of inflammatory infiltrate in cancers, the biological role of inflammation in prostate cancer development is not yet fully clarified. The characterization of molecular pathways that connect altered inflammatory response and prostate cancer progression can provide the scientific rationale for the identification of new prognostic and predictive biomarkers...

MOTIVATION: Drug combinations that simultaneously suppress multiple cancer driver signaling pathways increase therapeutic options and may reduce drug resistance. We have developed a computational systems biology tool, DrugComboExplorer, to identify driver signaling pathways and predict synergistic drug combinations by integrating the knowledge embedded in vast amounts of available pharmacogenomics and omics data. RESULTS: This tool generates driver signaling networks by processing DNA sequencing, gene copy number, DNA methylation, and RNA-seq data from individual cancer patients using an integrated pipeline of algorithms, including bootstrap aggregating-based Markov random field, weighted co-expression network analysis, and supervised regulatory network learning...

BACKGROUND: 68 Ga-PSMA-PET has an increasing importance in the evaluation of prostate cancer patients due to its high sensitivity and specificity in identifying neoplastic lesions in the clinical setting of elevated prostate-specific antigen (PSA). The objective of this study was to calculate the whole-body tumor burden using volumetric quantification of lesions detected in 68 Ga-PSMA-PET of prostate cancer patients with biochemical recurrence and correlate these findings with clinical and image parameters...

The hypoxic tumor microenvironment is the major contributor of chemotherapy resistance in solid tumors. One of the key regulators of hypoxic responses within the cell is the hypoxia inducible factor-1α (HIF-1α) that is involved in transcription of genes promoting cell survival and chemotherapy resistance. Multidrug resistance gene-1 (MDR1) and Lysosome-associated protein transmembrane 4B-35 (LAPTM4B-35) are among those notable players which augment their responses to cellular hypoxia. MDR1 is the hypoxia responsive gene involved in multidrug resistance phenotype while LAPTM4B-35 is involved in chemotherapy resistance by stabilizing HIF-1α and overexpressing MDR1...

Stem cell characteristics have been associated with treatment resistance and poor prognosis across many cancer types. The ability to induce and regulate the pathways that sustain these characteristic hallmarks of lethal cancers in a novel in vitro model would greatly enhance our understanding of cancer progression and treatment resistance. In this work, we present such a model, based simply on applying standard pluripotency/embryonic stem cell media alone. Core pluripotency stem cell master regulators (OCT4, SOX2 and NANOG) along with epithelial-mesenchymal transition (EMT) markers (Snail, Slug, vimentin and N-cadherin) were induced in human prostate, breast, lung, bladder, colorectal, and renal cancer cells...

OBJECTIVE: To evaluate the associationbetween anogenital distance (AGD), as a biomarker ofprenatal androgen milieu, and risk of prostate cancer(PCa). METHODS: A case-control study was conducted on260 men attending a university hospital where theyunderwent physical and andrological examination andcompleted a brief questionnaire. PCa patients were confirmedby biopsy of the tumor. Controls were men withoutPCa attending the urology outpatient clinic for routineexaminations...

Cell-free DNA (cfDNA), which are small DNA fragments in blood derived from dead cells including tumor cells, could serve as useful biomarkers and provide valuable genetic information about the tumors. cfDNA is now used for the genetic analysis of several types of cancers, as a surrogate for tumor biopsy, designated as "liquid biopsy." Rhabdomyosarcoma (RMS), the most frequent soft tissue tumor in childhood, can arise in any part of the body, and radiological imaging is the only available method for estimating the tumor burden, because no useful specific biological markers are present in the blood...

PURPOSE: To identify a novel biomarker that can predict biochemical recurrence (BCR) after radical prostatectomy. METHODS: The gene expression profile of SAMD5 in prostate cancer was explored based on the oncomine database and The Cancer Genomic Atlas (TCGA). The follow-up information and clinical pathologic variables were extracted from the following cohort study: TCGA_prostate carcinoma. And then, survival analysis was conducted using the Kaplan-Meier plot and Cox's proportional hazard regression model...

Isolation of specific single chain antibodies (scFvs) against key epitopes of cancer markers are applied for cancer immunotherapy and diagnosis. In this study following the prediction of the 3D structure of the DSP part of Dentin sialophosphoprotein (DSPP), the epitope was chosen using in silico programs. Panning process was applied to isolate specific human scFv against the epitope. PCR and DNA fingerprinting differentiated the specific clones, which were evaluated by phage ELISA. Following DNA sequencing, the 3D structure of isolated scFv was modeled and Docked on DSP...

Urological malignancies, including prostate cancer, bladder cancer and kidney cancer are major causes of morbidity and mortality worldwide. Because of the high incidence, diversity in biology, and especially direct interaction with urine, urological cancers are an important resource for both scientists and clinicians for novel diagnostic and therapeutic discovery. Extracellular vesicles (EVs) are lipid bilayer encapsulated particles released by cells into the extracellular space. Since EVs work as a safe way to transport important biological information through the whole body, they are now recognized as an important mechanism of cell-cell communication and have opened a new window for us to gain a better understanding of cancer biology, novel diagnostics, and/or therapeutic options...

Circular RNAs (circRNAs) are an intriguing class of RNA due to their covalently closed structure, high stability, and implicated roles in gene regulation. Here, we used an exome capture RNA sequencing protocol to detect and characterize circRNAs across >2,000 cancer samples. When compared against Ribo-Zero and RNase R, capture sequencing significantly enhanced the enrichment of circRNAs and preserved accurate circular-to-linear ratios. Using capture sequencing, we built the most comprehensive catalog of circRNA species to date: MiOncoCirc, the first database to be composed primarily of circRNAs directly detected in tumor tissues...

Acidity and hypoxia are crucial phenotypes of tumour microenvironment both contributing to the selection of malignant cells under a micro evolutionistic pressure. During the tumour progression, nanovesicles, called exosomes and the metalloenzyme carbonic anhydrase IX (CA IX) affect the tumour growth and proliferation. Exosomes are released into the tumour microenvironment and spilt all over the body, while CA IX is a tumour-associated protein overexpressed in many different solid tumours. In the present study, to better understand the relationships between exosomes and CA IX, it has been used an in vitro cellular model of cells cultured in different pH conditions...

PURPOSE: To investigate the prognostic value of neutrophil-to-lymphocyte ratio (NLR) for the selection of the optimal sequencing strategy using docetaxel and androgen receptor axis-targeted (ARAT) agents in patients with M0 or M1 castration-resistant prostate cancer (CRPC). Currently, there is a need to identify biomarkers to guide optimal sequential treatment in CRPC. METHODS: This multicenter, retrospective analysis included 303 consecutive patients initially diagnosed with M0 or M1 CRPC between September 2009 and March 2017...