Prostanoid receptor genes confer poor prognosis in head and neck squamous cell carcinoma via epigenetic inactivation

Misawa, Kiyoshi; Mima, Masato; Yamada, Satoshi; Imai, Atsushi; Mochizuki, Daiki; Ishikawa, Ryuji; Kita, Junya; Yamaguchi, Yuki; Endo, Shiori; Misawa, Yuki; Mineta, Hiroyuki

doi:10.1186/s12967-020-02214-1

Cited by 7 publications

(7 citation statements)

References 42 publications

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“…These ndings align with established knowledge concerning the role of promoter hypermethylation in gene silencing, which signi cantly contributes to the initiation of tumorigenesis. Our results further support the idea that hypermethylation of genes encoding prostaglandin receptors, exempli ed by PTGFR, seen in colorectal and ovarian cancers, could potentially redirect transcriptional disruption toward the activation of prostaglandin E2 (PGE2) function while blocking other biologically active prostaglandins 21,22 . This underscores the pivotal role of DNA methylation as a mechanism deeply involved in deregulating this pathway.…”

Section: Discussionsupporting

confidence: 81%

Bioinformatics analysis of GPCRs: A window into breast tumorigenesis and metastasis

Khan,

Hernández-González,

Murillo-González

et al. 2023

Preprint

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G-protein-coupled receptors (GPCRs) are known signal transducers and are increasingly implicated in tumorigenesis, but their precise roles in breast cancer progression remain underexplored. We scrutinized the mRNA expression profiles of fifty GPCRs in breast tumor tissue compared to normal tissue. Prominently, PTGFR, VIPR1, ADGRL2/3, LPAR1, and S1PR1 were found to be downregulated in breast cancer tissues, while ADGRL2 and CELSR1 exhibited upregulation. LPAR1, TSHR, and S1PR2/4 expression significantly influenced HPV and lncRNA entry in breast cancer compared to normal counterparts. We also explored correlations between GPCRs and various clinicopathological attributes, encompassing menopausal age, receptor status, nodal status, P53 status, triple-negative breast cancer (TNBC), Scarf–Bloom–Richardson grade (SBR), and nottingham prognostic index (NPI). Survival analysis unveiled thirty-three GPCRs that significantly influenced prognosis, with a high net alteration frequency of 84.41% across all 50 GPCRs. Our investigation unraveled complex co-expression associations between GPCRs and genes involved in pivotal signaling pathways, growth factor receptors, PKCs, GEFs, and markers indicative of metastasis and proliferation. Moreover, our study identified potential interactions between rutin, cucurbitacins, ellagic acid, and tilliroside with the targeted GPCRs. P2RY8, LPAR3, S1PR5, LPAR2, CELSR3, and GRM8 may function as oncogenes whereas, ADGRL2, LPAR1/4/6, and GRM6/7, PTGFR, TSHR, SMO, CCKBR, S1PR2/4 and CHRM1/3 may be tumor-suppressors for breast cancer.

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Section: Discussionsupporting

confidence: 81%

Bioinformatics analysis of GPCRs: A window into breast tumorigenesis and metastasis

Khan,

Hernández-González,

Murillo-González

et al. 2023

Preprint

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“…As candidate genes for the detection of hypopharyngeal cancer, we selected genes that were previously reported by comprehensive analyses [ 23 , 24 ] and systematic reviews [ 25 , 26 ] as being hypermethylated in tissue or saliva samples in advanced HNSCC cases. Four genes, Deleted in Colorectal Cancer ( DCC ) [ 21 , 27 ], Prostaglandin D2 Receptor 1 ( PTGDR1 ) [ 28 , 29 ], Endothelin Receptor β ( EDNRB ) [ 21 , 30 ], and E Cadherin ( ECAD ) [ 31 , 32 ], were selected for this study. Primers were designed to specifically amplify the bisulfite-converted DNA of each gene.…”

Section: Methodsmentioning

confidence: 99%

“…The forward and reverse sequences of each primer and β-actin ( ACTB ), as an internal reference gene, are listed in Supplementary Table S1 . These primers were previously determined to detect the methylation status of target gene promoters [ 21 , 28 – 32 ].…”

Section: Methodsmentioning

confidence: 99%

Methylation analysis of DCC gene in saliva samples is an efficient method for non-invasive detection of superficial hypopharyngeal cancer

Hirai,

Kinugasa,

Yamamoto

et al. 2024

Br J Cancer

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Background Advances in upper gastrointestinal endoscopic technology have enabled early detection and treatment of hypopharyngeal cancer. However, in-depth pharyngeal observations require sedation and are invasive. It is important to establish a minimally invasive and simple evaluation method to identify high-risk patients. Methods Eighty-seven patients with superficial hypopharyngeal cancer and 51 healthy controls were recruited. We assessed the methylation status of DCC, PTGDR1, EDNRB, and ECAD, in tissue and saliva samples and verified the diagnostic accuracy by methylation analyses of their promoter regions using quantitative methylation-specific PCR. Results Significant differences between cancer and their surrounding non-cancerous tissues were observed in the methylation values of DCC (p = 0.003), EDNRB (p = 0.001), and ECAD (p = 0.043). Using receiver operating characteristic analyses of the methylation values in saliva samples, DCC showed the highest area under the curve values for the detection of superficial hypopharyngeal cancer (0.917, 95% confidence interval = 0.864–0.970), compared with those for EDNRB (0.680) and ECAD (0.639). When the cutoff for the methylation values of DCC was set at ≥0.163, the sensitivity to detect hypopharyngeal cancer was 82.8% and the specificity was 90.2%. Conclusions DCC methylation in saliva samples could be a non-invasive and efficient tool for early detection of hypopharyngeal cancer in high-risk patients.

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“…A standard curve for quantitative real-time methylation and unmethylation PCR (Q-MSP and Q-UMSP) was constructed by plotting five serially diluted standard solutions of EpiScope Methylated HCT116 gDNA (TaKaRa, Tokyo, Japan) and EpiScope® Unmethylated HCT116 DKO gDNA (TaKaRa, Tokyo, Japan). The normalized methylation value (NMV) was defined as follows: NMV = (TSGs-S/TSGs-FM)/(ACTB-S/ACTB-FM), where TSGs-S and TSGs-FM represent TSGs methylation level in sample and universally methylated DNA, respectively, and ACTB-S and ACTB-FM correspond to β-actin levels in samples and universally methylated DNA, respectively [ 15 ]. Known amounts of LINE-1 methylated and unmethylated DNA molecules were used to generate absolute standard curves (y = − 6.125 * log(x) + 26.54 and y = − 2.765 * log(x) + 21.19, respectively).…”

Section: Methodsmentioning

confidence: 99%

Long interspersed nuclear element 1 hypomethylation has novel prognostic value and potential utility in liquid biopsy for oral cavity cancer

et al. 2020

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Background New biomarkers are urgently needed to improve personalized treatment approaches for head and neck squamous cell carcinoma (HNSCC). Global DNA hypomethylation has wide-ranging functions in multistep carcinogenesis, and the hypomethylation of long interspersed nucleotide element-1 (LINE-1) is related to increased retrotransposon activity and induced genome instability. However, little information is available regarding LINE-1 hypomethylation and its prognostic implications in HNSCC. Methods In this study, we analyzed LINE-1 hypomethylation levels in a well-characterized dataset of 317 primary HNSCC tissues and 225 matched pairs of normal mucosa tissues, along with five oral cavity cancer (OCC) circulating tumor DNA (ctDNA) samples using quantitative real-time methylation and unmethylation PCR. The analysis was performed according to various clinical characteristics and prognostic implications. Results The results demonstrated that LINE-1 hypomethylation levels were significantly higher in the HNSCC tissues than in corresponding normal tissues from the same individuals (P < 0.001). Univariate analysis revealed that high levels of LINE-1 hypomethylation were correlated with poor disease-free survival (DFS; log-rank test, P = 0.038), whereas multivariate analysis demonstrated that they were significant independent prognostic factor for DFS (hazard ratio: 2.10, 95% confidence interval: 1.02–4.36; P = 0.045). Moreover, samples with high LINE-1 hypomethylation levels exhibited the greatest decrease in 5-hydroxymethylcytosine (5-hmC) levels and increase in tumor-suppressor gene methylation index (P = 0.006 and P < 0.001, respectively). Further, ctDNA studies also showed that LINE-1 hypomethylation had high predictive ability in OCC. Conclusions LINE-1 hypomethylation is associated with a higher risk of early OCC relapse, and is hence, a potential predictive biomarker for OCC. Furthermore, 5-hmC levels also exhibited predictive potential in OCC, based on their inverse correlation with LINE-1 hypomethylation levels. LINE-1 hypomethylation analysis, therefore, has applications in determining patient prognosis and real-time surveillance of disease recurrence, and could serve as an alternative method for OCC screening.

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Prostanoid receptor genes confer poor prognosis in head and neck squamous cell carcinoma via epigenetic inactivation

Cited by 7 publications

References 42 publications

Bioinformatics analysis of GPCRs: A window into breast tumorigenesis and metastasis

Bioinformatics analysis of GPCRs: A window into breast tumorigenesis and metastasis

Methylation analysis of DCC gene in saliva samples is an efficient method for non-invasive detection of superficial hypopharyngeal cancer

Long interspersed nuclear element 1 hypomethylation has novel prognostic value and potential utility in liquid biopsy for oral cavity cancer

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