Gene expression profiles of ovarian low-grade serous carcinoma resemble those of fallopian tube epithelium

Chunping Qiu, Nan Lu, Xiao Wang, Qing Zhang, Cunzhong Yuan, Shi Yan, Samina Dongol, Yingwei Li, Xiaomei Sun, Chenggong Sun, Zhiwei Zhang, Wenxin - Zheng, Beihua Kong

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Objective: The cell of origin of ovarian low-grade serous carcinoma (LGSC) remains unclarified. Our recent morphologic and immunophenotypic study suggests that most LGSCs may be derived from the fallopian tube. The purpose of the current study was to gain further insight into the origin of LGSC at the molecular level. Methods: RNA-seq analysis was performed on a total of 31 tissue samples including LGSC (n = 6), serous borderline tumors (SBT, n = 6), fallopian tube epithelia (FTE, n = 5), ovarian surface epithelia (OSE, n = 4), and human peritoneal mesothelia (HPM, n = 4). HGSC cases (n = 6) served as a positive control. Gene expression profiles were compared and analyzed. To validate the findings from the gene expression array study, we selected the highly differentially expressed genes (PAX8, CDH1, FOXA2, and ARX) as well as those corresponding proteins and examined their expression levels in tissue samples of ovarian serous tumors, fallopian tube, ovarian surface epithelia, and peritoneal mesothelia. Results: Dendrograms revealed that OSE samples clustered with HPM, while ovarian serous tumors, including LGSC, SBT and high-grade serous carcinoma (HGSC), clustered with FTE. Furthermore, LGSC showed a significantly closer relationship with FTE than with OSE and HPM samples. PAX8, CDH1, and FOXA2 were highly and specifically expressed in serous tumors and FTE samples but not in OSE samples. In contrast, ARX was mainly expressed in OSE samples but not in FTE and serous tumors. Conclusions: The findings of the current study provide further evidence at a molecular level that the fallopian tube is likely the cellular source of LGSC. This finding may enable new prevention strategies, improve early detection, and allow novel therapies to be tested.

Original languageEnglish (US)
JournalGynecologic Oncology
DOIs
StateAccepted/In press - 2017
Externally publishedYes

Fingerprint

Fallopian Tubes
Transcriptome
Epithelium
Carcinoma
Neoplasms
RNA
Gene Expression

Keywords

  • Fallopian tube
  • High-grade serous carcinoma
  • Low-grade serous carcinoma
  • Ovarian surface epithelium
  • Peritoneal mesothelium
  • Serous borderline tumor

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Gene expression profiles of ovarian low-grade serous carcinoma resemble those of fallopian tube epithelium. / Qiu, Chunping; Lu, Nan; Wang, Xiao; Zhang, Qing; Yuan, Cunzhong; Yan, Shi; Dongol, Samina; Li, Yingwei; Sun, Xiaomei; Sun, Chenggong; Zhang, Zhiwei; Zheng, Wenxin -; Kong, Beihua.

In: Gynecologic Oncology, 2017.

Research output: Contribution to journalArticle

Qiu, Chunping ; Lu, Nan ; Wang, Xiao ; Zhang, Qing ; Yuan, Cunzhong ; Yan, Shi ; Dongol, Samina ; Li, Yingwei ; Sun, Xiaomei ; Sun, Chenggong ; Zhang, Zhiwei ; Zheng, Wenxin - ; Kong, Beihua. / Gene expression profiles of ovarian low-grade serous carcinoma resemble those of fallopian tube epithelium. In: Gynecologic Oncology. 2017.
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abstract = "Objective: The cell of origin of ovarian low-grade serous carcinoma (LGSC) remains unclarified. Our recent morphologic and immunophenotypic study suggests that most LGSCs may be derived from the fallopian tube. The purpose of the current study was to gain further insight into the origin of LGSC at the molecular level. Methods: RNA-seq analysis was performed on a total of 31 tissue samples including LGSC (n = 6), serous borderline tumors (SBT, n = 6), fallopian tube epithelia (FTE, n = 5), ovarian surface epithelia (OSE, n = 4), and human peritoneal mesothelia (HPM, n = 4). HGSC cases (n = 6) served as a positive control. Gene expression profiles were compared and analyzed. To validate the findings from the gene expression array study, we selected the highly differentially expressed genes (PAX8, CDH1, FOXA2, and ARX) as well as those corresponding proteins and examined their expression levels in tissue samples of ovarian serous tumors, fallopian tube, ovarian surface epithelia, and peritoneal mesothelia. Results: Dendrograms revealed that OSE samples clustered with HPM, while ovarian serous tumors, including LGSC, SBT and high-grade serous carcinoma (HGSC), clustered with FTE. Furthermore, LGSC showed a significantly closer relationship with FTE than with OSE and HPM samples. PAX8, CDH1, and FOXA2 were highly and specifically expressed in serous tumors and FTE samples but not in OSE samples. In contrast, ARX was mainly expressed in OSE samples but not in FTE and serous tumors. Conclusions: The findings of the current study provide further evidence at a molecular level that the fallopian tube is likely the cellular source of LGSC. This finding may enable new prevention strategies, improve early detection, and allow novel therapies to be tested.",
keywords = "Fallopian tube, High-grade serous carcinoma, Low-grade serous carcinoma, Ovarian surface epithelium, Peritoneal mesothelium, Serous borderline tumor",
author = "Chunping Qiu and Nan Lu and Xiao Wang and Qing Zhang and Cunzhong Yuan and Shi Yan and Samina Dongol and Yingwei Li and Xiaomei Sun and Chenggong Sun and Zhiwei Zhang and Zheng, {Wenxin -} and Beihua Kong",
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T1 - Gene expression profiles of ovarian low-grade serous carcinoma resemble those of fallopian tube epithelium

AU - Qiu, Chunping

AU - Lu, Nan

AU - Wang, Xiao

AU - Zhang, Qing

AU - Yuan, Cunzhong

AU - Yan, Shi

AU - Dongol, Samina

AU - Li, Yingwei

AU - Sun, Xiaomei

AU - Sun, Chenggong

AU - Zhang, Zhiwei

AU - Zheng, Wenxin -

AU - Kong, Beihua

PY - 2017

Y1 - 2017

N2 - Objective: The cell of origin of ovarian low-grade serous carcinoma (LGSC) remains unclarified. Our recent morphologic and immunophenotypic study suggests that most LGSCs may be derived from the fallopian tube. The purpose of the current study was to gain further insight into the origin of LGSC at the molecular level. Methods: RNA-seq analysis was performed on a total of 31 tissue samples including LGSC (n = 6), serous borderline tumors (SBT, n = 6), fallopian tube epithelia (FTE, n = 5), ovarian surface epithelia (OSE, n = 4), and human peritoneal mesothelia (HPM, n = 4). HGSC cases (n = 6) served as a positive control. Gene expression profiles were compared and analyzed. To validate the findings from the gene expression array study, we selected the highly differentially expressed genes (PAX8, CDH1, FOXA2, and ARX) as well as those corresponding proteins and examined their expression levels in tissue samples of ovarian serous tumors, fallopian tube, ovarian surface epithelia, and peritoneal mesothelia. Results: Dendrograms revealed that OSE samples clustered with HPM, while ovarian serous tumors, including LGSC, SBT and high-grade serous carcinoma (HGSC), clustered with FTE. Furthermore, LGSC showed a significantly closer relationship with FTE than with OSE and HPM samples. PAX8, CDH1, and FOXA2 were highly and specifically expressed in serous tumors and FTE samples but not in OSE samples. In contrast, ARX was mainly expressed in OSE samples but not in FTE and serous tumors. Conclusions: The findings of the current study provide further evidence at a molecular level that the fallopian tube is likely the cellular source of LGSC. This finding may enable new prevention strategies, improve early detection, and allow novel therapies to be tested.

AB - Objective: The cell of origin of ovarian low-grade serous carcinoma (LGSC) remains unclarified. Our recent morphologic and immunophenotypic study suggests that most LGSCs may be derived from the fallopian tube. The purpose of the current study was to gain further insight into the origin of LGSC at the molecular level. Methods: RNA-seq analysis was performed on a total of 31 tissue samples including LGSC (n = 6), serous borderline tumors (SBT, n = 6), fallopian tube epithelia (FTE, n = 5), ovarian surface epithelia (OSE, n = 4), and human peritoneal mesothelia (HPM, n = 4). HGSC cases (n = 6) served as a positive control. Gene expression profiles were compared and analyzed. To validate the findings from the gene expression array study, we selected the highly differentially expressed genes (PAX8, CDH1, FOXA2, and ARX) as well as those corresponding proteins and examined their expression levels in tissue samples of ovarian serous tumors, fallopian tube, ovarian surface epithelia, and peritoneal mesothelia. Results: Dendrograms revealed that OSE samples clustered with HPM, while ovarian serous tumors, including LGSC, SBT and high-grade serous carcinoma (HGSC), clustered with FTE. Furthermore, LGSC showed a significantly closer relationship with FTE than with OSE and HPM samples. PAX8, CDH1, and FOXA2 were highly and specifically expressed in serous tumors and FTE samples but not in OSE samples. In contrast, ARX was mainly expressed in OSE samples but not in FTE and serous tumors. Conclusions: The findings of the current study provide further evidence at a molecular level that the fallopian tube is likely the cellular source of LGSC. This finding may enable new prevention strategies, improve early detection, and allow novel therapies to be tested.

KW - Fallopian tube

KW - High-grade serous carcinoma

KW - Low-grade serous carcinoma

KW - Ovarian surface epithelium

KW - Peritoneal mesothelium

KW - Serous borderline tumor

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