Skip to main content
Erschienen in: Clinical and Translational Oncology 8/2017

15.03.2017 | Research Article

The expression of HDAC7 in cancerous gastric tissues is positively associated with distant metastasis and poor patient prognosis

verfasst von: Y. Yu, F. Cao, X. Yu, P. Zhou, Q. Di, J. Lei, Y. Tai, H. Wu, X. Li, X. Wang, W. Zhang, P. Li, Y. Li

Erschienen in: Clinical and Translational Oncology | Ausgabe 8/2017

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To characterize the expression patterns of HDAC7 in patients with gastric cancer and evaluate the prognostic value of HDAC7 in gastric cancer.

Methods

The expression of histone deacetylase 7 (HDAC7) was detected in paraffin-embedded gastric cancer samples from 86 patients by immunohistochemistry, and the differences in the expression of HDAC7 between cancerous and corresponding adjacent noncancerous tissues were compared using the Wilcoxon matched-pairs signed rank test. The correlation between HDAC7 expression and Ki-67 expression or clinicopathologic characteristics was evaluated using a Spearman rank correlation test. Prognostic outcomes that correlated with HDAC7 were examined using a Kaplan–Meier analysis and Cox proportional hazards model. Moreover, the effects of HDAC7 on the proliferation, migration and invasion of gastric cancer cells were investigated in vitro using human gastric carcinoma AGS cells.

Results

We found that HDAC7 was downregulated in cancerous gastric tissues (P = 0.0019). However, the expression of HDAC7 in cancerous gastric tissues positively correlated with Ki-67 expression (P = 0.0325) and distant metastasis (P = 0.020). Moreover, overall survival was shorter for patients expressing higher levels of HDAC7 in cancerous tissues (P = 0.042). Mechanistically, the disruption of the HDAC7 gene attenuated the capacity of cell growth, migration and invasion and induced G0/G1 arrest in AGS cells. Conversely, forced ovperexpression of HDAC7 promoted cell growth, migration and invasion and G1/S transition in AGS cells.

Conclusions

These results indicate that high HDAC7 expression in cancerous gastric tissues correlates with distant metastasis and predicts a poor prognosis for patients with gastric cancer.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
3.
6.
10.
Zurück zum Zitat Wang AH, Yang XJ. Histone deacetylase 4 possesses intrinsic nuclear import and export signals. Mol Cell Biol. 2001;21(17):5992–6005.CrossRef Wang AH, Yang XJ. Histone deacetylase 4 possesses intrinsic nuclear import and export signals. Mol Cell Biol. 2001;21(17):5992–6005.CrossRef
11.
Zurück zum Zitat McKinsey TA, Zhang CL, Olson EN. Identification of a signal-responsive nuclear export sequence in class II histone deacetylases. Mol Cell Biol. 2001;21(18):6312–21.CrossRef McKinsey TA, Zhang CL, Olson EN. Identification of a signal-responsive nuclear export sequence in class II histone deacetylases. Mol Cell Biol. 2001;21(18):6312–21.CrossRef
13.
Zurück zum Zitat Kao HY, Downes M, Ordentlich P, Evans RM. Isolation of a novel histone deacetylase reveals that class I and class II deacetylases promote SMRT-mediated repression. Genes Dev. 2000;14(1):55–66.PubMedPubMedCentral Kao HY, Downes M, Ordentlich P, Evans RM. Isolation of a novel histone deacetylase reveals that class I and class II deacetylases promote SMRT-mediated repression. Genes Dev. 2000;14(1):55–66.PubMedPubMedCentral
16.
Zurück zum Zitat Qian DZ, Kachhap SK, Collis SJ, Verheul HM, Carducci MA, Atadja P, et al. Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1 alpha. Cancer Res. 2006;66(17):8814–21. doi:10.1158/0008-5472.CAN-05-4598.CrossRefPubMed Qian DZ, Kachhap SK, Collis SJ, Verheul HM, Carducci MA, Atadja P, et al. Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1 alpha. Cancer Res. 2006;66(17):8814–21. doi:10.​1158/​0008-5472.​CAN-05-4598.CrossRefPubMed
21.
Zurück zum Zitat Osada H, Tatematsu Y, Saito H, Yatabe Y, Mitsudomi T, Takahashi T. Reduced expression of class II histone deacetylase genes is associated with poor prognosis in lung cancer patients. Int J Cancer. 2004;112(1):26–32. doi:10.1002/ijc.20395.CrossRefPubMed Osada H, Tatematsu Y, Saito H, Yatabe Y, Mitsudomi T, Takahashi T. Reduced expression of class II histone deacetylase genes is associated with poor prognosis in lung cancer patients. Int J Cancer. 2004;112(1):26–32. doi:10.​1002/​ijc.​20395.CrossRefPubMed
22.
Zurück zum Zitat Moreno DA, Scrideli CA, Cortez MA, de Paula Queiroz R, Valera ET, da Silva Silveira V, et al. Differential expression of HDAC3, HDAC7 and HDAC9 is associated with prognosis and survival in childhood acute lymphoblastic leukaemia. Br J Haematol. 2010;150(6):665–73. doi:10.1111/j.1365-2141.2010.08301.x.CrossRefPubMed Moreno DA, Scrideli CA, Cortez MA, de Paula Queiroz R, Valera ET, da Silva Silveira V, et al. Differential expression of HDAC3, HDAC7 and HDAC9 is associated with prognosis and survival in childhood acute lymphoblastic leukaemia. Br J Haematol. 2010;150(6):665–73. doi:10.​1111/​j.​1365-2141.​2010.​08301.​x.CrossRefPubMed
23.
Zurück zum Zitat Weichert W, Roske A, Gekeler V, Beckers T, Ebert MP, Pross M, et al. Association of patterns of class I histone deacetylase expression with patient prognosis in gastric cancer: a retrospective analysis. Lancet Oncol. 2008;9(2):139–48. doi:10.1016/S1470-2045(08)70004-4.CrossRefPubMed Weichert W, Roske A, Gekeler V, Beckers T, Ebert MP, Pross M, et al. Association of patterns of class I histone deacetylase expression with patient prognosis in gastric cancer: a retrospective analysis. Lancet Oncol. 2008;9(2):139–48. doi:10.​1016/​S1470-2045(08)70004-4.CrossRefPubMed
26.
Zurück zum Zitat Yu J, Cheng YY, Tao Q, Cheung KF, Lam CN, Geng H, et al. Methylation of protocadherin 10, a novel tumor suppressor, is associated with poor prognosis in patients with gastric cancer. Gastroenterol. 2009;136(2):640–51. doi:10.1053/j.gastro.2008.10.050.CrossRef Yu J, Cheng YY, Tao Q, Cheung KF, Lam CN, Geng H, et al. Methylation of protocadherin 10, a novel tumor suppressor, is associated with poor prognosis in patients with gastric cancer. Gastroenterol. 2009;136(2):640–51. doi:10.​1053/​j.​gastro.​2008.​10.​050.CrossRef
27.
Zurück zum Zitat Weidner N, Moore DH 2nd, Vartanian R. Correlation of Ki-67 antigen expression with mitotic figure index and tumor grade in breast carcinomas using the novel “paraffin”-reactive MIB1 antibody. Hum Pathol. 1994;25(4):337–42.CrossRef Weidner N, Moore DH 2nd, Vartanian R. Correlation of Ki-67 antigen expression with mitotic figure index and tumor grade in breast carcinomas using the novel “paraffin”-reactive MIB1 antibody. Hum Pathol. 1994;25(4):337–42.CrossRef
29.
Zurück zum Zitat Mayer B, Johnson JP, Leitl F, Jauch KW, Heiss MM, Schildberg FW, et al. E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res. 1993;53(7):1690–5.PubMed Mayer B, Johnson JP, Leitl F, Jauch KW, Heiss MM, Schildberg FW, et al. E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res. 1993;53(7):1690–5.PubMed
Metadaten
Titel
The expression of HDAC7 in cancerous gastric tissues is positively associated with distant metastasis and poor patient prognosis
verfasst von
Y. Yu
F. Cao
X. Yu
P. Zhou
Q. Di
J. Lei
Y. Tai
H. Wu
X. Li
X. Wang
W. Zhang
P. Li
Y. Li
Publikationsdatum
15.03.2017
Verlag
Springer International Publishing
Erschienen in
Clinical and Translational Oncology / Ausgabe 8/2017
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-017-1639-9

Weitere Artikel der Ausgabe 8/2017

Clinical and Translational Oncology 8/2017 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.