A novel molecular signature identifies mixed subtypes in renal cell carcinoma with poor prognosis and independent response to immunotherapy.

Background: Renal cell carcinoma (RCC) is a heterogeneous disease comprising histologically defined subtypes. For therapy selection, precise subtype identification and individualized prognosis are mandatory, but currently limited. Our aim was to refine subtyping and outcome prediction across main subtypes, assuming that a tumor is composed of molecular features present in distinct pathological subtypes.

Cadherin switches during epithelial-mesenchymal transition: CDH4/RCAD downregulation reduces bladder cancer progression.

Purpose: Non-muscle invasive bladder cancer (NMIBC) is a highly recurrent disease that progresses to muscle-invasive bladder cancer (MIBC) in 5-25% of the cases. Epithelial-mesenchymal transition (EMT) has been associated with features of disease progression. Thus, we aimed to characterize the cadherin switch (CS), an EMT hallmark, and its regulatory mechanisms in bladder cancer (BlCa) progression, as well as the biological role of RCAD, a lesser-known cadherin, in bladder carcinogenesis.

Discovery of Volatile Biomarkers for Bladder Cancer Detection and Staging through Urine Metabolomics.

Timely diagnosis is crucial to improve the long-term survival of bladder cancer (BC) patients. The discovery of new BC biomarkers based in urine analysis is very attractive because this biofluid is in direct contact with the inner bladder layer, in which most of the neoplasms develop, and is non-invasively collected. Hence, this work aimed to unveil alterations in the urinary volatile profile of patients diagnosed with BC compared with cancer-free individuals, as well as differences among patients diagnosed at different tumor stages, to identify candidate biomarkers for non-invasive BC diagnosis and staging.

Urinary Volatilomics Unveils a Candidate Biomarker Panel for Noninvasive Detection of Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer usually associated with asymptomatic development and risk of systemic progression. Hence, reliable molecular biomarkers of ccRCC are needed to provide early and minimally invasive detection. In this study, urinary volatilome profiling of patients diagnosed with ccRCC ( = 75), and cancer-free controls ( = 75), was performed to investigate the presence of a volatile signature characteristic of ccRCC.

Tackling tumor microenvironment through epigenetic tools to improve cancer immunotherapy.

Background: Epigenetic alterations are known contributors to cancer development and aggressiveness. Additional to alterations in cancer cells, aberrant epigenetic marks are present in cells of the tumor microenvironment, including lymphocytes and tumor-associated macrophages, which are often overlooked but known to be a contributing factor to a favorable environment for tumor growth. Therefore, the main aim of this review is to give an overview of the epigenetic alterations affecting immune cells in the tumor microenvironment to provoke an immunosuppressive function and contribute to cancer development.

Circulating extracellular vesicles release oncogenic miR-424 in experimental models and patients with aggressive prostate cancer.

Extracellular vesicles (EVs) are relevant means for transferring signals across cells and facilitate propagation of oncogenic stimuli promoting disease evolution and metastatic spread in cancer patients. Here, we investigated the release of miR-424 in circulating small EVs or exosomes from prostate cancer patients and assessed the functional implications in multiple experimental models. We found higher frequency of circulating miR-424 positive EVs in patients with metastatic prostate cancer compared to patients with primary tumors and BPH.

Circulating miR-30b-5p levels in plasma as a novel potential biomarker for early detection of breast cancer.

Background: Recently, microRNAs have been demonstrated to be potential non-invasive biomarkers for diagnosis, prognosis assessment or prediction of response to treatment in cancer. In this study, we evaluate the potential of miR-30b-5p as a biomarker for early diagnosis of breast cancer (BC) in tissue and plasma.

Methods: Expression of miR-30b-5p was determined in a series of 112 BC and 40 normal breast tissues.

JmjC-KDMs KDM3A and KDM6B modulate radioresistance under hypoxic conditions in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC), the most frequent esophageal cancer (EC) subtype, entails dismal prognosis. Hypoxia, a common feature of advanced ESCC, is involved in resistance to radiotherapy (RT). RT response in hypoxia might be modulated through epigenetic mechanisms, constituting novel targets to improve patient outcome.

Circulating miR-99a-5p Expression in Plasma: A Potential Biomarker for Early Diagnosis of Breast Cancer.

MicroRNAs have emerged as new diagnostic and therapeutic biomarkers for breast cancer. Herein, we analysed miR-99a-5p expression levels in primary tumours and plasma of breast cancer patients to evaluate its usefulness as a minimally invasive diagnostic biomarker. MiR-99a-5p expression levels were determined by quantitative real-time PCR in three independent cohorts of patients: (I) Discovery cohort: breast cancer tissues ( = 103) and healthy breast tissues ( = 26); (II) Testing cohort: plasma samples from 105 patients and 98 healthy donors; (III) Validation cohort: plasma samples from 89 patients and 85 healthy donors.

Clinicopathological and imaging features of pulmonary alveolar microlithiasis in a dog - a case report.

Background: The aetiology of pulmonary alveolar microlithiasis (PAM) in animals is still unknown. In humans, this pulmonary disorder is a rare autosomal recessive disorder triggered by a mutation in the gene SLC34A2, which causes deposition and aggregation of calcium and phosphate in the pulmonary parenchyma with formation of microliths. Although histopathological examination is required for a definite diagnosis, in humans, imaging modalities such as computed tomography can demonstrate typical patterns of the disease.

The disruption of protein-protein interactions as a therapeutic strategy for prostate cancer.

Prostate cancer (PCa) is one of the most common male-specific cancers worldwide, with high morbidity and mortality rates associated with advanced disease stages. The current treatment options of PCa are prostatectomy, hormonal therapy, chemotherapy or radiotherapy, the selection of which is usually dependent upon the stage of the disease. The development of PCa to a castration-resistant phenotype (CRPC) is associated with a more severe prognosis requiring the development of a new and effective therapy.

Renal Cell Tumors: Uncovering the Biomarker Potential of ncRNAs.

Renal cell tumors (RCT) remain as one of the most common and lethal urological tumors worldwide. Discrimination between (1) benign and malignant disease, (2) indolent and aggressive tumors, and (3) patient responsiveness to a specific therapy is of major clinical importance, allowing for a more efficient patient management. Nonetheless, currently available tools provide limited information and novel strategies are needed.

DNA Methylation as a Therapeutic Target for Bladder Cancer.

Bladder cancer (BC) is the tenth most frequent cancer worldwide and is associated with high mortality when diagnosed in its most aggressive form, which is not reverted by the current treatment options. Thus, the development of new therapeutic strategies, either alternative or complementary to the current ones, is of major importance. The disruption of normal epigenetic mechanisms, namely, DNA methylation, is a known early event in cancer development.

MicroRNA-30a-5p: a novel diagnostic and prognostic biomarker for clear cell renal cell carcinoma in tissue and urine samples.

Background: The rising incidence of renal cell carcinomas (RCC) constitutes a significant challenge owing to risk of overtreatment. Because aberrant microRNA (miR) promoter methylation contributes to cancer development, we investigated whether altered miR-30a-5p expression associates with DNA promoter methylation and evaluated the usefulness as clear cell RCC (ccRCC) diagnostic and prognostic markers.

Methods: Genome-wide methylome and RNA sequencing data from a set of ccRCC and normal tissue samples from The Cancer Genome Atlas (TCGA) database were integrated to identify candidate CpG loci involved in cancer onset.

Volatilomics Reveals Potential Biomarkers for Identification of Renal Cell Carcinoma: An In Vitro Approach.

The identification of noninvasive biomarkers able to detect renal cell carcinoma (RCC) at an early stage remains an unmet clinical need. The recognition that altered metabolism is a core hallmark of cancer boosted metabolomic studies focused in the search for cancer biomarkers. The present work aims to evaluate the performance of the volatile metabolites present in the extracellular medium to discriminate RCC cell lines with distinct histological subtypes (clear cell and papillary) and metastatic potential from non-tumorigenic renal cells.

Sirtuins' Deregulation in Bladder Cancer: SIRT7 Is Implicated in Tumor Progression through Epithelial to Mesenchymal Transition Promotion.

Sirtuins are emerging players in cancer biology and other age-related disorders, and their putative role in bladder cancer (BlCa) remains elusive. Further understanding of disease biology may allow for generation of more effective pathway-based biomarkers and targeted therapies. Herein, we aimed to illuminate the role of sirtuins' family in BlCa and evaluate their potential as disease biomarkers and therapeutic targets.

Lactate Increases Renal Cell Carcinoma Aggressiveness through Sirtuin 1-Dependent Epithelial Mesenchymal Transition Axis Regulation.

Background: Renal cell carcinoma (RCC) displays a glycolytic phenotype (Warburg effect). Increased lactate production, impacting on tumor biology and microenvironment modulation, has been implicated in epigenetic mechanisms' regulation, leading to histone deacetylases inhibition. Thus, in-depth knowledge of lactate's impact on epigenome regulation of highly glycolytic tumors might allow for new therapeutic strategies.

Analysis of Epigenetic Alterations in Homologous Recombination DNA Repair Genes in Male Breast Cancer.

Background: Male breast cancer (BC) is a distinct neoplasm with low but rising incidence, frequently diagnosed as advanced stage disease. Considering the relevance of altered homologous recombination repair (HRR) in male BC, we aimed to explore the biomarker potential of aberrant promoter methylation of , , , and .

Methods: Formalin-fixed paraffin-embedded (FFPE) tissue samples from 128 male BC patients, paired adjacent normal tissue and 19 gynecomastia cases were collected and assessed by quantitative methylation-specific PCR (qMSP).

DNA Methylation-Based Testing in Liquid Biopsies as Detection and Prognostic Biomarkers for the Four Major Cancer Types.

Lung, breast, colorectal, and prostate cancers are the most incident worldwide. Optimal population-based cancer screening methods remain an unmet need, since cancer detection at early stages increases the prospects of successful and curative treatment, leading to a lower incidence of recurrences. Moreover, the current parameters for cancer patients' stratification have been associated with divergent outcomes.

The metabolic landscape of urological cancers: New therapeutic perspectives.

Deregulation of cell metabolism is an established cancer hallmark that contributes to tumor initiation and progression, as well as tumor heterogeneity. In solid tumors, alterations in different metabolic pathways, including glycolysis, pentose phosphate pathway, glutaminolysis and fatty acid metabolism, support the high proliferative rates and macromolecule biosynthesis of cancer cells. Despite advances in therapy, urothelial tumors still exhibit high recurrence and mortality rates, especially in advanced stages of disease.

Digital imaging-assisted quantification of H3K27me3 immunoexpression in luminal A/B-like, HER2-negative, invasive breast cancer predicts patient survival and risk of recurrence.

Background: Breast cancer (BC) is a major health concern and better understanding of its biology might improve treatment decisions and patient outcomes. Histone3 Lysine27 tri-methylation (H3K27me3) is a post-translational histone modification frequently associated with altered gene expression. In BC patients, lower H3K27me3 expression has been associated with worse prognosis.

Early detection of the major male cancer types in blood-based liquid biopsies using a DNA methylation panel.

Background: Lung (LC), prostate (PCa) and colorectal (CRC) cancers are the most incident in males worldwide. Despite recent advances, optimal population-based cancer screening methods remain an unmet need. Due to its early onset, cancer specificity and accessibility in body fluids, aberrant DNA promoter methylation might be a valuable minimally invasive tool for early cancer detection.

The Critical Role of Hypoxic Microenvironment and Epigenetic Deregulation in Esophageal Cancer Radioresistance.

Esophageal cancer (EC) is the seventh most common cancer worldwide and the sixth leading cause of death, according to Globocan 2018. Despite efforts made for therapeutic advances, EC remains highly lethal, portending a five-year overall survival of just 15-20%. Hence, the discovery of new molecular targets that might improve therapeutic efficacy is urgently needed.