Aquaporin-1 promoter hypermethylation is associated with improved prognosis in salivary gland adenoid cystic carcinoma

Marietta Tan, Chunbo Shao, Justin A. Bishop, Zhaoyong Feng, Bruce J. Trock, William H. Westra, Patrick K. Ha

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Objectives. Aquaporin-1 (AQP1) is a candidate oncogene that is epigenetically modified in adenoid cystic carcinoma (ACC). We sought to (1) assess AQP1 promoter methylation and expression in an ACC cohort, (2) identify correlations between AQP1 and clinical outcomes, and (3) explore the role of AQP1 in tumor progression in vitro. Study design. Laboratory study, retrospective chart review. Setting. Academic medical center. Methods. DNA and RNA were isolated from ACC tumors and control salivary gland tissues. Quantitative methylationspecific polymerase chain reaction (PCR) was performed on bisulfite-treated DNA. Quantitative reverse transcription PCR was performed after cDNA synthesis. Cell lines stably overexpressing an AQP1 plasmid or empty vector were generated. Cell scratch and Matrigel invasion assays were performed. Retrospective chart review was performed for collection of clinical information. Results. Methylation results from 77 tumors and 30 controls demonstrated that AQP1 was hypomethylated in tumors (P < .0001). Fifty-eight tumors (75.3%) displayed AQP1 hypomethylation compared with controls. AQP1 expression levels assessed in 58 tumors and 23 controls demonstrated a trend toward increased expression in tumors (P = .08). Univariate analysis revealed that AQP1 hypermethylation was associated with increased overall survival. No associations between AQP1 expression level and survival were found. AQP1 overexpression did not affect cell migratory or invasive capacities in vitro. Conclusion. AQP1 promoter hypomethylation is common in ACC, and AQP1 tends to be overexpressed in these tumors. Increased AQP1 methylation is associated with improved prognosis on univariate analysis, but expression is not associated with outcomes. Further in vitro studies are necessary to clarify the role of AQP1 in ACC.

Original languageEnglish (US)
Pages (from-to)801-807
Number of pages7
JournalOtolaryngology - Head and Neck Surgery (United States)
Volume150
Issue number5
DOIs
StatePublished - Jan 1 2014

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Aquaporin 1
Adenoid Cystic Carcinoma
Salivary Glands
Neoplasms
Methylation
Polymerase Chain Reaction
DNA

Keywords

  • adenoid cystic carcinoma
  • epigenetics
  • promoter methylation

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Surgery

Cite this

Aquaporin-1 promoter hypermethylation is associated with improved prognosis in salivary gland adenoid cystic carcinoma. / Tan, Marietta; Shao, Chunbo; Bishop, Justin A.; Feng, Zhaoyong; Trock, Bruce J.; Westra, William H.; Ha, Patrick K.

In: Otolaryngology - Head and Neck Surgery (United States), Vol. 150, No. 5, 01.01.2014, p. 801-807.

Research output: Contribution to journalArticle

Tan, Marietta ; Shao, Chunbo ; Bishop, Justin A. ; Feng, Zhaoyong ; Trock, Bruce J. ; Westra, William H. ; Ha, Patrick K. / Aquaporin-1 promoter hypermethylation is associated with improved prognosis in salivary gland adenoid cystic carcinoma. In: Otolaryngology - Head and Neck Surgery (United States). 2014 ; Vol. 150, No. 5. pp. 801-807.
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abstract = "Objectives. Aquaporin-1 (AQP1) is a candidate oncogene that is epigenetically modified in adenoid cystic carcinoma (ACC). We sought to (1) assess AQP1 promoter methylation and expression in an ACC cohort, (2) identify correlations between AQP1 and clinical outcomes, and (3) explore the role of AQP1 in tumor progression in vitro. Study design. Laboratory study, retrospective chart review. Setting. Academic medical center. Methods. DNA and RNA were isolated from ACC tumors and control salivary gland tissues. Quantitative methylationspecific polymerase chain reaction (PCR) was performed on bisulfite-treated DNA. Quantitative reverse transcription PCR was performed after cDNA synthesis. Cell lines stably overexpressing an AQP1 plasmid or empty vector were generated. Cell scratch and Matrigel invasion assays were performed. Retrospective chart review was performed for collection of clinical information. Results. Methylation results from 77 tumors and 30 controls demonstrated that AQP1 was hypomethylated in tumors (P < .0001). Fifty-eight tumors (75.3{\%}) displayed AQP1 hypomethylation compared with controls. AQP1 expression levels assessed in 58 tumors and 23 controls demonstrated a trend toward increased expression in tumors (P = .08). Univariate analysis revealed that AQP1 hypermethylation was associated with increased overall survival. No associations between AQP1 expression level and survival were found. AQP1 overexpression did not affect cell migratory or invasive capacities in vitro. Conclusion. AQP1 promoter hypomethylation is common in ACC, and AQP1 tends to be overexpressed in these tumors. Increased AQP1 methylation is associated with improved prognosis on univariate analysis, but expression is not associated with outcomes. Further in vitro studies are necessary to clarify the role of AQP1 in ACC.",
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T1 - Aquaporin-1 promoter hypermethylation is associated with improved prognosis in salivary gland adenoid cystic carcinoma

AU - Tan, Marietta

AU - Shao, Chunbo

AU - Bishop, Justin A.

AU - Feng, Zhaoyong

AU - Trock, Bruce J.

AU - Westra, William H.

AU - Ha, Patrick K.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Objectives. Aquaporin-1 (AQP1) is a candidate oncogene that is epigenetically modified in adenoid cystic carcinoma (ACC). We sought to (1) assess AQP1 promoter methylation and expression in an ACC cohort, (2) identify correlations between AQP1 and clinical outcomes, and (3) explore the role of AQP1 in tumor progression in vitro. Study design. Laboratory study, retrospective chart review. Setting. Academic medical center. Methods. DNA and RNA were isolated from ACC tumors and control salivary gland tissues. Quantitative methylationspecific polymerase chain reaction (PCR) was performed on bisulfite-treated DNA. Quantitative reverse transcription PCR was performed after cDNA synthesis. Cell lines stably overexpressing an AQP1 plasmid or empty vector were generated. Cell scratch and Matrigel invasion assays were performed. Retrospective chart review was performed for collection of clinical information. Results. Methylation results from 77 tumors and 30 controls demonstrated that AQP1 was hypomethylated in tumors (P < .0001). Fifty-eight tumors (75.3%) displayed AQP1 hypomethylation compared with controls. AQP1 expression levels assessed in 58 tumors and 23 controls demonstrated a trend toward increased expression in tumors (P = .08). Univariate analysis revealed that AQP1 hypermethylation was associated with increased overall survival. No associations between AQP1 expression level and survival were found. AQP1 overexpression did not affect cell migratory or invasive capacities in vitro. Conclusion. AQP1 promoter hypomethylation is common in ACC, and AQP1 tends to be overexpressed in these tumors. Increased AQP1 methylation is associated with improved prognosis on univariate analysis, but expression is not associated with outcomes. Further in vitro studies are necessary to clarify the role of AQP1 in ACC.

AB - Objectives. Aquaporin-1 (AQP1) is a candidate oncogene that is epigenetically modified in adenoid cystic carcinoma (ACC). We sought to (1) assess AQP1 promoter methylation and expression in an ACC cohort, (2) identify correlations between AQP1 and clinical outcomes, and (3) explore the role of AQP1 in tumor progression in vitro. Study design. Laboratory study, retrospective chart review. Setting. Academic medical center. Methods. DNA and RNA were isolated from ACC tumors and control salivary gland tissues. Quantitative methylationspecific polymerase chain reaction (PCR) was performed on bisulfite-treated DNA. Quantitative reverse transcription PCR was performed after cDNA synthesis. Cell lines stably overexpressing an AQP1 plasmid or empty vector were generated. Cell scratch and Matrigel invasion assays were performed. Retrospective chart review was performed for collection of clinical information. Results. Methylation results from 77 tumors and 30 controls demonstrated that AQP1 was hypomethylated in tumors (P < .0001). Fifty-eight tumors (75.3%) displayed AQP1 hypomethylation compared with controls. AQP1 expression levels assessed in 58 tumors and 23 controls demonstrated a trend toward increased expression in tumors (P = .08). Univariate analysis revealed that AQP1 hypermethylation was associated with increased overall survival. No associations between AQP1 expression level and survival were found. AQP1 overexpression did not affect cell migratory or invasive capacities in vitro. Conclusion. AQP1 promoter hypomethylation is common in ACC, and AQP1 tends to be overexpressed in these tumors. Increased AQP1 methylation is associated with improved prognosis on univariate analysis, but expression is not associated with outcomes. Further in vitro studies are necessary to clarify the role of AQP1 in ACC.

KW - adenoid cystic carcinoma

KW - epigenetics

KW - promoter methylation

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