Apoptosis inhibitor-5 overexpression is associated with tumor progression and poor prognosis in patients with cervical cancer

Hanbyoul Cho, Joon Yong Chung, Kwon Ho Song, Kyung H. Noh, Bo Wook Kim, Eun Joo Chung, Kris Ylaya, Jin Hee Kim, Tae Woo Kim, Stephen M. Hewitt, Jae-Hoon Kim

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: The apoptosis inhibitor-5 (API5), anti-apoptosis protein, is considered a key molecule in the tumor progression and malignant phenotype of tumor cells. Here, we investigated API5 expression in cervical cancer, its clinical significance, and its relationship with phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2) in development and progression of cervical cancer.Methods: API5 effects on cell growth were assessed in cervical cancer cell lines. API5 and pERK1/2 immunohistochemical staining were performed on a cervical cancer tissue microarray consisting of 173 primary cervical cancers, 306 cervical intraepithelial neoplasias (CINs), and 429 matched normal tissues.Results: API5 overexpression promoted cell proliferation and colony formation in CaSki cells, whereas API5 knockdown inhibited the both properties in HeLa cells. Immunohistochemical staining showed that API5 expression increased during the normal to tumor transition of cervical carcinoma (P < 0.001), and this increased expression was significantly associated with tumor stage (P = 0.004), tumor grade (P < 0.001), and chemo-radiation response (P = 0.004). API5 expression levels were positively associated with pERK1/2 in cervical cancer (P < 0.001) and high grade CIN (P = 0.031). In multivariate analysis, API5+ (P = 0.039) and combined API5+/pERK1/2+ (P = 0.032) were independent prognostic factors for overall survival.Conclusions: API5 expression is associated with pERK1/2 in a subset of cervical cancer patients and its expression predicts poor overall survival, supporting that API5 may be a promising novel target for therapeutic interventions.

Original languageEnglish
Article number545
JournalBMC cancer
Volume14
Issue number1
DOIs
Publication statusPublished - 2014 Jul 28

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Uterine Cervical Neoplasms
Apoptosis
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Neoplasms
Cervical Intraepithelial Neoplasia
Staining and Labeling
Survival
HeLa Cells
Multivariate Analysis
Cell Proliferation
Radiation
Carcinoma
Phenotype
Cell Line

All Science Journal Classification (ASJC) codes

  • Oncology
  • Genetics
  • Cancer Research

Cite this

Cho, Hanbyoul ; Chung, Joon Yong ; Song, Kwon Ho ; Noh, Kyung H. ; Kim, Bo Wook ; Chung, Eun Joo ; Ylaya, Kris ; Kim, Jin Hee ; Kim, Tae Woo ; Hewitt, Stephen M. ; Kim, Jae-Hoon. / Apoptosis inhibitor-5 overexpression is associated with tumor progression and poor prognosis in patients with cervical cancer. In: BMC cancer. 2014 ; Vol. 14, No. 1.
@article{57738d21743048afae2052005b8edeb9,
title = "Apoptosis inhibitor-5 overexpression is associated with tumor progression and poor prognosis in patients with cervical cancer",
abstract = "Background: The apoptosis inhibitor-5 (API5), anti-apoptosis protein, is considered a key molecule in the tumor progression and malignant phenotype of tumor cells. Here, we investigated API5 expression in cervical cancer, its clinical significance, and its relationship with phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2) in development and progression of cervical cancer.Methods: API5 effects on cell growth were assessed in cervical cancer cell lines. API5 and pERK1/2 immunohistochemical staining were performed on a cervical cancer tissue microarray consisting of 173 primary cervical cancers, 306 cervical intraepithelial neoplasias (CINs), and 429 matched normal tissues.Results: API5 overexpression promoted cell proliferation and colony formation in CaSki cells, whereas API5 knockdown inhibited the both properties in HeLa cells. Immunohistochemical staining showed that API5 expression increased during the normal to tumor transition of cervical carcinoma (P < 0.001), and this increased expression was significantly associated with tumor stage (P = 0.004), tumor grade (P < 0.001), and chemo-radiation response (P = 0.004). API5 expression levels were positively associated with pERK1/2 in cervical cancer (P < 0.001) and high grade CIN (P = 0.031). In multivariate analysis, API5+ (P = 0.039) and combined API5+/pERK1/2+ (P = 0.032) were independent prognostic factors for overall survival.Conclusions: API5 expression is associated with pERK1/2 in a subset of cervical cancer patients and its expression predicts poor overall survival, supporting that API5 may be a promising novel target for therapeutic interventions.",
author = "Hanbyoul Cho and Chung, {Joon Yong} and Song, {Kwon Ho} and Noh, {Kyung H.} and Kim, {Bo Wook} and Chung, {Eun Joo} and Kris Ylaya and Kim, {Jin Hee} and Kim, {Tae Woo} and Hewitt, {Stephen M.} and Jae-Hoon Kim",
year = "2014",
month = "7",
day = "28",
doi = "10.1186/1471-2407-14-545",
language = "English",
volume = "14",
journal = "BMC Cancer",
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Cho, H, Chung, JY, Song, KH, Noh, KH, Kim, BW, Chung, EJ, Ylaya, K, Kim, JH, Kim, TW, Hewitt, SM & Kim, J-H 2014, 'Apoptosis inhibitor-5 overexpression is associated with tumor progression and poor prognosis in patients with cervical cancer', BMC cancer, vol. 14, no. 1, 545. https://doi.org/10.1186/1471-2407-14-545

Apoptosis inhibitor-5 overexpression is associated with tumor progression and poor prognosis in patients with cervical cancer. / Cho, Hanbyoul; Chung, Joon Yong; Song, Kwon Ho; Noh, Kyung H.; Kim, Bo Wook; Chung, Eun Joo; Ylaya, Kris; Kim, Jin Hee; Kim, Tae Woo; Hewitt, Stephen M.; Kim, Jae-Hoon.

In: BMC cancer, Vol. 14, No. 1, 545, 28.07.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Apoptosis inhibitor-5 overexpression is associated with tumor progression and poor prognosis in patients with cervical cancer

AU - Cho, Hanbyoul

AU - Chung, Joon Yong

AU - Song, Kwon Ho

AU - Noh, Kyung H.

AU - Kim, Bo Wook

AU - Chung, Eun Joo

AU - Ylaya, Kris

AU - Kim, Jin Hee

AU - Kim, Tae Woo

AU - Hewitt, Stephen M.

AU - Kim, Jae-Hoon

PY - 2014/7/28

Y1 - 2014/7/28

N2 - Background: The apoptosis inhibitor-5 (API5), anti-apoptosis protein, is considered a key molecule in the tumor progression and malignant phenotype of tumor cells. Here, we investigated API5 expression in cervical cancer, its clinical significance, and its relationship with phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2) in development and progression of cervical cancer.Methods: API5 effects on cell growth were assessed in cervical cancer cell lines. API5 and pERK1/2 immunohistochemical staining were performed on a cervical cancer tissue microarray consisting of 173 primary cervical cancers, 306 cervical intraepithelial neoplasias (CINs), and 429 matched normal tissues.Results: API5 overexpression promoted cell proliferation and colony formation in CaSki cells, whereas API5 knockdown inhibited the both properties in HeLa cells. Immunohistochemical staining showed that API5 expression increased during the normal to tumor transition of cervical carcinoma (P < 0.001), and this increased expression was significantly associated with tumor stage (P = 0.004), tumor grade (P < 0.001), and chemo-radiation response (P = 0.004). API5 expression levels were positively associated with pERK1/2 in cervical cancer (P < 0.001) and high grade CIN (P = 0.031). In multivariate analysis, API5+ (P = 0.039) and combined API5+/pERK1/2+ (P = 0.032) were independent prognostic factors for overall survival.Conclusions: API5 expression is associated with pERK1/2 in a subset of cervical cancer patients and its expression predicts poor overall survival, supporting that API5 may be a promising novel target for therapeutic interventions.

AB - Background: The apoptosis inhibitor-5 (API5), anti-apoptosis protein, is considered a key molecule in the tumor progression and malignant phenotype of tumor cells. Here, we investigated API5 expression in cervical cancer, its clinical significance, and its relationship with phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2) in development and progression of cervical cancer.Methods: API5 effects on cell growth were assessed in cervical cancer cell lines. API5 and pERK1/2 immunohistochemical staining were performed on a cervical cancer tissue microarray consisting of 173 primary cervical cancers, 306 cervical intraepithelial neoplasias (CINs), and 429 matched normal tissues.Results: API5 overexpression promoted cell proliferation and colony formation in CaSki cells, whereas API5 knockdown inhibited the both properties in HeLa cells. Immunohistochemical staining showed that API5 expression increased during the normal to tumor transition of cervical carcinoma (P < 0.001), and this increased expression was significantly associated with tumor stage (P = 0.004), tumor grade (P < 0.001), and chemo-radiation response (P = 0.004). API5 expression levels were positively associated with pERK1/2 in cervical cancer (P < 0.001) and high grade CIN (P = 0.031). In multivariate analysis, API5+ (P = 0.039) and combined API5+/pERK1/2+ (P = 0.032) were independent prognostic factors for overall survival.Conclusions: API5 expression is associated with pERK1/2 in a subset of cervical cancer patients and its expression predicts poor overall survival, supporting that API5 may be a promising novel target for therapeutic interventions.

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DO - 10.1186/1471-2407-14-545

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