ABSTRACT
Prostate cancer (PCa) remains the most commonly diagnosed cancer in men worldwide and is still the second leading cause of cancer-related death. One major cause of PCa development is epigenetic aberration, including histone modification. We have previously demonstrated that Lysine Demethylase 5C (KDM5C) plays an essential role in the development of PCa and drives PCa progression by promoting epithelial-mesenchymal transition. Epigenetic regulators often work in concert, for example, to regulate transcription. We identified Paraspeckle Component 1 (PSPC1) as an interacting protein of KDM5C, suggesting that these proteins might function together in PCa. Here, we systematically investigate the expression patterns of KDM5C and PSPC1 in 2 independent prostate cohorts (432 and 205 prostate tumors in total for PSPC1 and KDM5C, respectively) by immunohistochemistry. We demonstrate that the expression of PSPC1 correlates with that of KDM5C. In addition, PSPC1 is up-regulated in primary and metastatic PCa. Elevated PSPC1 expression correlates with a higher-grade group and an advanced T-stage. Patients with high PSPC1 expression have a worse biochemical recurrence-free survival. In addition, PSPC1 expression is an independent prognostic parameter. Our data indicate that KDM5C and PSPC1 are involved in PCa progression, and therapeutic inhibition of KDM5C and PSPC1 by selective compounds might be a promising approach for the treatment of PCa.
Subject(s)
Prostatic Neoplasms , Male , Humans , Prostate , Epithelial-Mesenchymal Transition , RNA-Binding Proteins , Histone DemethylasesABSTRACT
Colorectal cancer is a notorious disease, with almost half of the patients succumbing to the disease. The prevalence and incidence rates of colorectal cancer are increasing in many parts of the world, highlighting the need to discover new biomarkers for diagnosis and therapy. Caldesmon (CaD), an actin-binding protein that plays a significant role in controlling cell motility, has emerged as a promising biomarker. The CALD1 gene encodes CaD as multiple transcripts that mainly encode two protein isoforms: High-molecular-weight (h-CaD), expressed in smooth muscle, and low-molecular-weight (l-CaD), expressed in nonsmooth muscle cells. Most studies have suggested an oncogenic role of CaD in colorectal cancer, but the exact subcellular localization of the two CaD isoforms in tumor cells and stroma have not been clarified yet. Here, we analyzed tissue samples from 262 colorectal cancer patients by immunohistochemistry analysis using specific antibodies for l-CaD and h-CaD. The results showed elevated cytoplasmic expression levels of l-Cad in 187/262 (71.4%) cases. l-Cad was expressed at low levels in the normal colon mucosa and was also consistently expressed in the cancer-associated stroma of all cases, suggesting that it could play a role in modulating the tumor microenvironment. l-CaD expression in cancer cells was associated with preinvasive stages of cancer. Survival analysis indicated that patients with high l-CaD expression in tumor cells could respond poorly to selective chemotherapeutic 5FU, but not combination chemotherapy. h-CaD was expressed in colonic and vascular smooth muscle cells as expected and to a lesser extent in the tumor-associated stroma, but it was not expressed in the cancer cells or normal colon mucosal epithelial cells. Collectively, these data clarify how the expression patterns of CaD isoforms in colorectal cancer can have applications in the management of colorectal cancer patients.
Subject(s)
Calmodulin-Binding Proteins , Colorectal Neoplasms , Humans , Calmodulin-Binding Proteins/genetics , Calmodulin-Binding Proteins/metabolism , Protein Isoforms/genetics , Protein Isoforms/metabolism , Cell Movement/physiology , Epithelial Cells/metabolism , Colorectal Neoplasms/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Tumor MicroenvironmentABSTRACT
Head and neck squamous cell carcinomas (HNSCC) are among the most common cancers worldwide and are associated with a poor prognosis for patients. Among HNSCC, those originating in the hypopharynx have the worst prognosis. The histone demethylase LSD1 has been shown to promote cancer initiation, progression, and relapse through various mechanisms and is upregulated in many cancer tissues. LSD1 physically interacts with SNAIL and is required for SNAIL mediated transcriptional repression. Previous studies of the prognostic value of LSD1 in HNSCC have been limited in their analysis of sub-sites, and a correlation between LSD1 and SNAIL has not been shown in HNSCC patient samples. Here we used a large, representative, and clinically well-characterized cohort of 339 HNSCC patients to investigate the co-expression of LSD1 and SNAIL and their prognostic value in all HNSCC using immunohistochemical staining. Elevated LSD1 expression correlated with advanced tumor stage and poor progression-free survival (PFS) in HNSCC originating in the hypopharynx. Overexpression of the transcription factor SNAIL independently correlated with worse overall survival (OS) and PFS in HNSCC in general and prominently in tumors of the hypopharynx. Furthermore, increased LSD1 expression significantly correlated with elevated SNAIL expression in patient samples. Therefore, the presented data implicates LSD1 and SNAIL as independent prognostic biomarkers.
