Global <scp>DNA</scp> hypomethylation is associated with the development and poor prognosis of tongue squamous cell carcinoma

Chen, Hung-Chih; Yang, Chung‐Yi; Cheng, Jiin‐Tsuey; Fu, Ting‐Ying; Liou, Horng-Huei; Tseng, Hui‐Hwa; Lee, Jang-Hwa; Li, Guancheng; Wang, Jyh-Seng; Hou, Yu‐Yi; Weng, Ta-Jung; Ger, Luo‐Ping

doi:10.1111/jop.12381

Cited by 19 publications

(18 citation statements)

References 61 publications

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“…This is in accordance with results from an earlier small-scale study that also found no prognostic value for 5mC immunoreactivity in PC ( n = 48) [ 39 ]. In contrast, global loss of 5mC has been associated with poor prognosis in tongue squamous cell carcinoma [ 45 ], while increased 5mC levels in myelodysplastic syndrome have been linked with a worse prognosis [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Dysregulation and prognostic potential of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) levels in prostate cancer

et al. 2018

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BackgroundPrognostic tools for prostate cancer (PC) are inadequate and new molecular biomarkers may improve risk stratification. The epigenetic mark 5-hydroxymethylcytosine (5hmC) has recently been proposed as a novel candidate prognostic biomarker in several malignancies including PC. 5hmC is an oxidized derivative of 5-methylcytosine (5mC) and can be further oxidized to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). The present study is the first to investigate the biomarker potential in PC for all four DNA methylation marks in parallel. Thus, we determined 5mC, 5hmC, 5fC, and 5caC levels in non-malignant (NM) and PC tissue samples from a large radical prostatectomy (RP) patient cohort (n = 546) by immunohistochemical (IHC) analysis of serial sections of a tissue microarray. Possible associations between methylation marks, routine clinicopathological parameters, ERG status, and biochemical recurrence (BCR) after RP were investigated.Results5mC and 5hmC levels were significantly reduced in PC compared to NM prostate tissue samples (p ≤ 0.027) due to a global loss of both marks specifically in ERG− PCs. 5fC levels were significantly increased in ERG+ PCs (p = 0.004), whereas 5caC levels were elevated in both ERG− and ERG+ PCs compared with NM prostate tissue samples (p ≤ 0.019). Positive correlations were observed between 5mC, 5fC, and 5caC levels in both NM and PC tissues (p < 0.001), while 5hmC levels were only weakly positively correlated to 5mC in the PC subset (p = 0.030). There were no significant associations between 5mC, 5fC, or ERG status and time to BCR in this RP cohort. In contrast, high 5hmC levels were associated with BCR in ERG− PCs (p = 0.043), while high 5caC levels were associated with favorable prognosis in ERG+ PCs (p = 0.011) and were borderline significantly associated with worse prognosis in ERG− PCs (p = 0.058). Moreover, a combined high-5hmC/high-5caC score was a significant adverse predictor of post-operative BCR beyond routine clinicopathological variables in ERG− PCs (hazard ratio 3.18 (1.54–6.56), p = 0.002, multivariate Cox regression).ConclusionsThis is the first comprehensive study of 5mC, 5hmC, 5fC, and 5caC levels in PC and the first report of a significant prognostic potential for 5caC in PC.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0540-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Dysregulation and prognostic potential of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) levels in prostate cancer

et al. 2018

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“…The detailed procedures of tissue microarray (TMA) construction were described in our previous study [ 15 ]. The TMA block consisted of 129 cores, including 43 trios with each trio containing 2 cores from the tumor tissue and 1 core from the non-cancerous epithelium of the same patient.…”

Section: Methodsmentioning

confidence: 99%

Vimentin is a potential prognostic factor for tongue squamous cell carcinoma among five epithelial–mesenchymal transition-related proteins

Liu

Kang

et al. 2017

PLoS ONE

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We aimed to investigate the association of the expression levels of five epithelial–mesenchymal transition (EMT)-related proteins (Snail, Twist, E-cadherin, N-cadherin, and Vimentin) with tumorigenesis, pathologic parameters and prognosis in tongue squamous cell carcinoma (TSCC) patients by immunohistochemistry of tissue microarray. The expression levels of Snail, E-cadherin, N-cadherin and Vimentin were significantly different between the tumor adjacent normal and tumor tissues. In tumor tissues, lower E-cadherin and higher N-cadherin levels were associated with a higher grade of cell differentiation, advanced stage of disease, and lymph node metastasis. However, higher Vimentin expression was associated with poor cell differentiation and lymph node metastasis. Patients with low E-cadherin expression had poor disease-specific survival (DSS). Conversely, positive N-cadherin and higher Vimentin expression levels were associated with poor DSS and disease-free survival. Notably, our multivariate Cox regression model indicated that high Vimentin expression was an adverse prognostic factor for DSS in TSCC patients, even after the adjustment for cell differentiation, pathological stage, and expression levels of Snail, Twist, E-cadherin, and N-cadherin. Snail, E-cadherin, N-cadherin, and Vimentin were associated with tumorigenesis and pathological outcomes. Among the five EMT-related proteins, Vimentin was a potential prognostic factor for TSCC patients.

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“…TMA blocks were cut into 4-μm paraffin sections, dewaxed in xylene, rehydrated through a series of graded alcohols, and subsequently washed for 5 minutes with phosphate-buffered saline (PBS) [ 50 ]. The Novolink max polymer detection system (Leica, Newcastle Upon Tyne, United Kingdom) was used for the following immunostaining processes.…”

Section: Methodsmentioning

confidence: 99%

Subsite-specific association of DEAD box RNA helicase DDX60 with the development and prognosis of oral squamous cell carcinoma

Sie

et al. 2016

Oncotarget

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The clinical significance and biological function of DEXD/H box helicase 60 (DDX60) in oral cancer remains unknown. Herein, we evaluated the association of DDX60 expression with tumorigenesis and the prognosis of oral squamous cell carcinoma (OSCC). DDX60 expression was examined by immunohistochemistry on tissue microarray slides of 494 OSCC patients, including 180 buccal mucosal SCC (BMSCC), 241 tongue SCC (TSCC), and 73 lip SCC (LSCC) patients. DDX60 expression was significantly increased in all three subsites of OSCC compared to its expression in tumor adjacent normal tissues. However, its association with tumorigenesis was specific to the oral cavity subsite after the stratification of betel quid chewing, smoking, and drinking. Among OSCC patients, higher levels of DDX60 expression were associated with the male gender, a well-differentiated tumor, advanced stage of disease, and a large tumor size with subsite specific features. LSCC patients with high DDX60 expression levels showed shorter disease-specific survival, particularly those with moderately or poorly differentiated tumors. Additionally, TSCC or OSCC patients with high DDX60 expression showed a poor disease-free survival (DFS), particularly those with moderately or poorly differentiated tumors. Therefore, DDX60 is a novel and unfavorable biomarker for tumorigenesis and prognosis of OSCC in a subsite-specific manner.

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Global DNA hypomethylation is associated with the development and poor prognosis of tongue squamous cell carcinoma

Abstract: Global hypomethylation was an independent biomarker for the development and poor prognosis of TSCC.

Cited by 19 publications

References 61 publications

Dysregulation and prognostic potential of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) levels in prostate cancer

Dysregulation and prognostic potential of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) levels in prostate cancer

Vimentin is a potential prognostic factor for tongue squamous cell carcinoma among five epithelial–mesenchymal transition-related proteins

Subsite-specific association of DEAD box RNA helicase DDX60 with the development and prognosis of oral squamous cell carcinoma

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