MICA/B and ULBP1 NKG2D ligands are independent predictors of good prognosis in cervical cancer

Hanbyoul Cho, Joon Yong Chung, Sunghoon Kim, Till Braunschweig, Tae Heung Kang, Jennie Kim, Eun Joo Chung, Stephen M. Hewitt, Jae Hoon Kim

Research output: Contribution to journalArticle

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Abstract

Background: NKG2D (natural killer group 2, member D) is thought to play an important role in mediating the activation of anticancer immune response. Expression of NKG2D ligands (NKG2DLs) is pronounced in malignancies and the heterogeneity of NKG2DL expression remains unclear. Here, we investigate the expression and clinical significance of NKG2DLs in cervical cancer. Methods: Immunohistochemical analyses of MICA/B, ULBP1, ULBP2, ULBP3, RAET1E, and RAET1G were performed using tissue microarray analysis of 200 cervical cancers, 327 high-grade cervical intraepithelial neoplasias (CINs), 99 low-grade CINs, and 541 matched nonadjacent normal cervical epithelial tissues and compared the data with clinicopathologic variables, including the survival of cervical cancer patients. Results: MICA/B, ULBP1, and RAET1E expression was higher in cervical cancer than in low-grade CIN (p<0.001, p=0.012, p=0.013, respectively) and normal cervix (all p<0.001). Among these markers, expression of ULBP1 was significantly different depending on patient tumor stage (p=0.010) and tumor size (p=0.045). ULBP1 expression was correlated with MICA/B (p<0.001) and ULBP2 (p=0.002) expression in cervical cancer. While MICA/B+ or ULBP1+ patients had improved disease-free survival time (p=0.027 and p=0.009, respectively) relative to that of the low expression group, RAET1E+ or RAET1G+ was correlated with shorter survival time (p=0.018 and p=0.029, respectively). However, in terms of overall survival, the ULBP1+ group had significantly longer survival time than the low expression group (p=0.009). Multivariate analysis indicated that MICA/B+/ULBP1+ (HR=0.16, p=0.015) and ULBP1+ (HR=0.31, p=0.024) are independent prognostic factors of disease-free survival in cervical cancer. Conclusions: High expression of either ULBP1 or MICA/B and ULBP1 combined is an indicator of good prognosis in cervical cancer, suggesting their potential utility as prognostic tests in clinical assessment.

Original languageEnglish
Article number957
JournalBMC cancer
Volume14
Issue number1
DOIs
Publication statusPublished - 2014 Dec 15

Fingerprint

Uterine Cervical Neoplasms
Ligands
Cervical Intraepithelial Neoplasia
Survival
Disease-Free Survival
Tissue Array Analysis
Neoplasms
Cervix Uteri
Multivariate Analysis
Epithelium

All Science Journal Classification (ASJC) codes

  • Genetics
  • Oncology
  • Cancer Research

Cite this

Cho, Hanbyoul ; Chung, Joon Yong ; Kim, Sunghoon ; Braunschweig, Till ; Kang, Tae Heung ; Kim, Jennie ; Chung, Eun Joo ; Hewitt, Stephen M. ; Kim, Jae Hoon. / MICA/B and ULBP1 NKG2D ligands are independent predictors of good prognosis in cervical cancer. In: BMC cancer. 2014 ; Vol. 14, No. 1.
@article{94fb6019b05e4847a898b7f340dcbab8,
title = "MICA/B and ULBP1 NKG2D ligands are independent predictors of good prognosis in cervical cancer",
abstract = "Background: NKG2D (natural killer group 2, member D) is thought to play an important role in mediating the activation of anticancer immune response. Expression of NKG2D ligands (NKG2DLs) is pronounced in malignancies and the heterogeneity of NKG2DL expression remains unclear. Here, we investigate the expression and clinical significance of NKG2DLs in cervical cancer. Methods: Immunohistochemical analyses of MICA/B, ULBP1, ULBP2, ULBP3, RAET1E, and RAET1G were performed using tissue microarray analysis of 200 cervical cancers, 327 high-grade cervical intraepithelial neoplasias (CINs), 99 low-grade CINs, and 541 matched nonadjacent normal cervical epithelial tissues and compared the data with clinicopathologic variables, including the survival of cervical cancer patients. Results: MICA/B, ULBP1, and RAET1E expression was higher in cervical cancer than in low-grade CIN (p<0.001, p=0.012, p=0.013, respectively) and normal cervix (all p<0.001). Among these markers, expression of ULBP1 was significantly different depending on patient tumor stage (p=0.010) and tumor size (p=0.045). ULBP1 expression was correlated with MICA/B (p<0.001) and ULBP2 (p=0.002) expression in cervical cancer. While MICA/B+ or ULBP1+ patients had improved disease-free survival time (p=0.027 and p=0.009, respectively) relative to that of the low expression group, RAET1E+ or RAET1G+ was correlated with shorter survival time (p=0.018 and p=0.029, respectively). However, in terms of overall survival, the ULBP1+ group had significantly longer survival time than the low expression group (p=0.009). Multivariate analysis indicated that MICA/B+/ULBP1+ (HR=0.16, p=0.015) and ULBP1+ (HR=0.31, p=0.024) are independent prognostic factors of disease-free survival in cervical cancer. Conclusions: High expression of either ULBP1 or MICA/B and ULBP1 combined is an indicator of good prognosis in cervical cancer, suggesting their potential utility as prognostic tests in clinical assessment.",
author = "Hanbyoul Cho and Chung, {Joon Yong} and Sunghoon Kim and Till Braunschweig and Kang, {Tae Heung} and Jennie Kim and Chung, {Eun Joo} and Hewitt, {Stephen M.} and Kim, {Jae Hoon}",
year = "2014",
month = "12",
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doi = "10.1186/1471-2407-14-957",
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Cho, H, Chung, JY, Kim, S, Braunschweig, T, Kang, TH, Kim, J, Chung, EJ, Hewitt, SM & Kim, JH 2014, 'MICA/B and ULBP1 NKG2D ligands are independent predictors of good prognosis in cervical cancer', BMC cancer, vol. 14, no. 1, 957. https://doi.org/10.1186/1471-2407-14-957

MICA/B and ULBP1 NKG2D ligands are independent predictors of good prognosis in cervical cancer. / Cho, Hanbyoul; Chung, Joon Yong; Kim, Sunghoon; Braunschweig, Till; Kang, Tae Heung; Kim, Jennie; Chung, Eun Joo; Hewitt, Stephen M.; Kim, Jae Hoon.

In: BMC cancer, Vol. 14, No. 1, 957, 15.12.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - MICA/B and ULBP1 NKG2D ligands are independent predictors of good prognosis in cervical cancer

AU - Cho, Hanbyoul

AU - Chung, Joon Yong

AU - Kim, Sunghoon

AU - Braunschweig, Till

AU - Kang, Tae Heung

AU - Kim, Jennie

AU - Chung, Eun Joo

AU - Hewitt, Stephen M.

AU - Kim, Jae Hoon

PY - 2014/12/15

Y1 - 2014/12/15

N2 - Background: NKG2D (natural killer group 2, member D) is thought to play an important role in mediating the activation of anticancer immune response. Expression of NKG2D ligands (NKG2DLs) is pronounced in malignancies and the heterogeneity of NKG2DL expression remains unclear. Here, we investigate the expression and clinical significance of NKG2DLs in cervical cancer. Methods: Immunohistochemical analyses of MICA/B, ULBP1, ULBP2, ULBP3, RAET1E, and RAET1G were performed using tissue microarray analysis of 200 cervical cancers, 327 high-grade cervical intraepithelial neoplasias (CINs), 99 low-grade CINs, and 541 matched nonadjacent normal cervical epithelial tissues and compared the data with clinicopathologic variables, including the survival of cervical cancer patients. Results: MICA/B, ULBP1, and RAET1E expression was higher in cervical cancer than in low-grade CIN (p<0.001, p=0.012, p=0.013, respectively) and normal cervix (all p<0.001). Among these markers, expression of ULBP1 was significantly different depending on patient tumor stage (p=0.010) and tumor size (p=0.045). ULBP1 expression was correlated with MICA/B (p<0.001) and ULBP2 (p=0.002) expression in cervical cancer. While MICA/B+ or ULBP1+ patients had improved disease-free survival time (p=0.027 and p=0.009, respectively) relative to that of the low expression group, RAET1E+ or RAET1G+ was correlated with shorter survival time (p=0.018 and p=0.029, respectively). However, in terms of overall survival, the ULBP1+ group had significantly longer survival time than the low expression group (p=0.009). Multivariate analysis indicated that MICA/B+/ULBP1+ (HR=0.16, p=0.015) and ULBP1+ (HR=0.31, p=0.024) are independent prognostic factors of disease-free survival in cervical cancer. Conclusions: High expression of either ULBP1 or MICA/B and ULBP1 combined is an indicator of good prognosis in cervical cancer, suggesting their potential utility as prognostic tests in clinical assessment.

AB - Background: NKG2D (natural killer group 2, member D) is thought to play an important role in mediating the activation of anticancer immune response. Expression of NKG2D ligands (NKG2DLs) is pronounced in malignancies and the heterogeneity of NKG2DL expression remains unclear. Here, we investigate the expression and clinical significance of NKG2DLs in cervical cancer. Methods: Immunohistochemical analyses of MICA/B, ULBP1, ULBP2, ULBP3, RAET1E, and RAET1G were performed using tissue microarray analysis of 200 cervical cancers, 327 high-grade cervical intraepithelial neoplasias (CINs), 99 low-grade CINs, and 541 matched nonadjacent normal cervical epithelial tissues and compared the data with clinicopathologic variables, including the survival of cervical cancer patients. Results: MICA/B, ULBP1, and RAET1E expression was higher in cervical cancer than in low-grade CIN (p<0.001, p=0.012, p=0.013, respectively) and normal cervix (all p<0.001). Among these markers, expression of ULBP1 was significantly different depending on patient tumor stage (p=0.010) and tumor size (p=0.045). ULBP1 expression was correlated with MICA/B (p<0.001) and ULBP2 (p=0.002) expression in cervical cancer. While MICA/B+ or ULBP1+ patients had improved disease-free survival time (p=0.027 and p=0.009, respectively) relative to that of the low expression group, RAET1E+ or RAET1G+ was correlated with shorter survival time (p=0.018 and p=0.029, respectively). However, in terms of overall survival, the ULBP1+ group had significantly longer survival time than the low expression group (p=0.009). Multivariate analysis indicated that MICA/B+/ULBP1+ (HR=0.16, p=0.015) and ULBP1+ (HR=0.31, p=0.024) are independent prognostic factors of disease-free survival in cervical cancer. Conclusions: High expression of either ULBP1 or MICA/B and ULBP1 combined is an indicator of good prognosis in cervical cancer, suggesting their potential utility as prognostic tests in clinical assessment.

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U2 - 10.1186/1471-2407-14-957

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