Aberrant Methylation Inactivates Somatostatin and Somatostatin Receptor Type 1 in Head and Neck Squamous Cell Carcinoma

Abstract

PurposeThe aim of this study was to define somatostatin (SST) and somatostatin receptor type 1 (SSTR1) methylation profiles for head and neck squamous cell carcinoma (HNSCC) tumors at diagnosis and follow up and to evaluate their prognostic significance and value as a biomarker.MethodsGene expression was measured by quantitative RT-PCR. Promoter methylation status was determined by quantitative methylation-specific PCR (Q-MSP) in HNSCC.ResultsMethylation was associated with transcription inhibition. SST methylation in 81% of HNSCC tumor specimens significantly correlated with tumor size (P = 0.043), stage (P = 0.008), galanin receptor type 2 (GALR2) methylation (P = 0.041), and tachykinin-1 (TAC1) (P = 0.040). SSTR1 hypermethylation in 64% of cases was correlated with tumor size (P = 0.037), stage (P = 0.037), SST methylation (P < 0.001), and expression of galanin (P = 0.03), GALR2 (P = 0.014), TAC1 (P = 0.023), and tachykinin receptor type 1 (TACR1) (P = 0.003). SST and SSTR1 promoter hypermethylation showed highly discriminating receiver operator characteristic curve profiles, which clearly distinguished HNSCC from adjacent normal mucosal tissues. Concurrent hypermethylation of galanin and SSTR1 promoters correlated with reduced disease-free survival (log-rank test, P = 0.0001). Among patients with oral cavity and oropharynx cancer, methylation of both SST and SSTR1 promoters correlated with reduced disease-free survival (log-rank test, P = 0.028). In multivariate logistic-regression analysis, concomitant methylation of galanin and SSTR1 was associated with an odds ratio for recurrence of 12.53 (95% CI, 2.62 to 59.8; P = 0.002).ConclusionsCpG hypermethylation is a likely mechanism of SST and SSTR1 gene inactivation, supporting the hypothesis that SST and SSTR1 play a role in the tumorigenesis of HNSCC and that this hypermethylation may serve as an important biomarker.

A Novel Gene Signature-Based Model Predicts Biochemical Recurrence-Free Survival in Prostate Cancer Patients after Radical Prostatectomy

“…For instance, ASNS, one risk biomarker in our study, was reported to function as a therapeutic target in castration-resistant prostate cancer [27]. SSTR1 was widely related to the progression of various cancers [28][29][30], and also functions as a prognostic marker in prostate cancer [31,32]. TRIM14 has been reported to promote invasion in glioblastoma [33] and colorectal cancer [34].…”

Integrated Epigenomics Analysis Reveals a DNA Methylation Panel for Endometrial Cancer Detection Using Cervical Scrapings

“…In the list of 180 genes, CDH13, COL14A1, HAAO, HAND2, HS3ST2, HTR1B, NPY, and ZNF177, have been reported in endometrial cancer samples in independent studies (17-19, 21, 27). Because different cancers may have common pathways, the hypermethylated genes identified in our gene list might also be methylated in other cancers, and ADHFE1, CDO1, DPP6, EFS, FEZF2, GHSR, GRIA4, NEFL, PARP15, PAX6, SSTR1, and TRH have been reported (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). We have identified for the first time hypermethylation of BHLHE22, CCDC140, CELF4, GALNTL6, ZNF334, and ZNF662 in cancers.…”

Genome-wide DNA Methylation Profiling Reveals Methylation Markers Associated with 3q Gain for Detection of Cervical Precancer and Cancer

“…Methylation of ZIC1 has been described previously for other tumor types, such as thyroid, ovarian, colon, and gastric cancer (43)(44)(45)(46). SST or somatostatin functions as an inhibitor with antisecretory, antiproliferative, and antiangiogenic effects (47) and is, in addition to cervical cancer, also found to be methylated in gastric, esophageal, colon, and head and neck cancer (48)(49)(50)(51). The biological function and expression regulation of these 3 genes in HPV-transformed cells remains to be determined.…”