Skip to main content
Top
Published in: Pathology & Oncology Research 4/2018

01-10-2018 | Original Article

Eukaryotic Elongation Factor 2 (eEF2) is a Potential Biomarker of Prostate Cancer

Authors: Xuefeng Zhang, Linkun Hu, Mingzhan Du, Xuedong Wei, Jun Zhang, Yu Hui, Cheng Chen, Gang Li, Jianquan Hou

Published in: Pathology & Oncology Research | Issue 4/2018

Login to get access

Abstract

Eukaryotic elongation factor 2 (eEF2), a key regulator of protein synthesis, is involved in the progression of several types of cancer. This first study was to investigate the relationships between eEF2 protein and prostate cancer (PCa). Immunohistochemical staining was used to verify eEF2 protein in a set of 97 formalin-fixed, paraffin-embedded primary PCa tissues. Expression of eEF2 protein in positive cells was characterized by cytoplasmic staining. Correlations with clinicopathological factors were evaluated by Chi-square or Fisher’s exact probability tests. eEF2 protein was found in 74 out of 97 (76.29%) patients. eEF2-positive had higher PSA and Gleason score than negative in all patients. In addition, the positive expression of eEF2 protein was significantly associated with PSA and Gleason score (P = 0.007 and 0.002). However, no significant correlations occurred between expression of eEF2 protein and TNM stage (P = 0.292). In those eEF2 protein-positive patients, we have found staining intensity of eEF2 protein was not only associated with PSA and Gleason score, but also associated with TNM stage (P = 0, 0.014 and 0.001, respectively). To conclude, our study indicates that expression of eEF2 protein is a potential biomarker for evaluating PCa.
Literature
2.
go back to reference Zhu Y, Wang HK, Qu YY, Ye DW (2015) Prostate cancer in East Asia: evolving trend over the last decade. Asian J Androl 17:48–57CrossRefPubMed Zhu Y, Wang HK, Qu YY, Ye DW (2015) Prostate cancer in East Asia: evolving trend over the last decade. Asian J Androl 17:48–57CrossRefPubMed
3.
go back to reference Sundi D, Schaeffer EM (2016) Progress in prognosis and prediction for men with prostate cancer. Eur Urol 22:30761–30768 Sundi D, Schaeffer EM (2016) Progress in prognosis and prediction for men with prostate cancer. Eur Urol 22:30761–30768
4.
go back to reference Grzmil M, Hemmings BA (2012) Translation regulation as a therapeutic target in cancer. Cancer Res 72:3891–3900CrossRefPubMed Grzmil M, Hemmings BA (2012) Translation regulation as a therapeutic target in cancer. Cancer Res 72:3891–3900CrossRefPubMed
5.
go back to reference Tash JS, Chakrasali R, Jakkaraj SR, Hughes J, Smith SK, Hornbaker K, Heckert LL, Ozturk SB, Hadden MK, Kinzy TG, Blagg BS, Georg GL (2008) Gamendazole, an orally active indazole carboxylic acid male contraceptive agent, targets HSP90AB1(HSP90BETA) and EEF1A (eEF1A) and stimulates II 1a transcription in rat sertoli cells. Biol Reprod 78:1139–1152CrossRefPubMed Tash JS, Chakrasali R, Jakkaraj SR, Hughes J, Smith SK, Hornbaker K, Heckert LL, Ozturk SB, Hadden MK, Kinzy TG, Blagg BS, Georg GL (2008) Gamendazole, an orally active indazole carboxylic acid male contraceptive agent, targets HSP90AB1(HSP90BETA) and EEF1A (eEF1A) and stimulates II 1a transcription in rat sertoli cells. Biol Reprod 78:1139–1152CrossRefPubMed
6.
go back to reference Tomlison VA, Newbery HJ, Wray NR, Jackson J, Larionov A, Miller WR, Dixon JM, Abbott CM (2005) Translation elongation factor eEF1A2 is a potential oncoprotein that is overexpressed in two-thirds of breast tumors. BMC Cancer 5:113–119CrossRef Tomlison VA, Newbery HJ, Wray NR, Jackson J, Larionov A, Miller WR, Dixon JM, Abbott CM (2005) Translation elongation factor eEF1A2 is a potential oncoprotein that is overexpressed in two-thirds of breast tumors. BMC Cancer 5:113–119CrossRef
7.
go back to reference Nakamura J, Aoyagi S, Nanchi I, Nakatsuka S, Hirata E, Shibata S, Fukuda M, Yamamoto Y, Fukuda I, Tatsumi N, Ueda T, Fujiki F, Nomura M, Nishida S, Shirakata T, Hosen N, Tsuboi A, Oka Y, Nezu R, Mori M, Doki Y, Aozasa K, Sugiyama H, Oji Y (2009) Overexpression of eukaryotic elongation factor eEF2 in gastrointestinal cancers and its involvement in G2/M progression in the cell cycle. Int J Oncol 34:1181–1189PubMed Nakamura J, Aoyagi S, Nanchi I, Nakatsuka S, Hirata E, Shibata S, Fukuda M, Yamamoto Y, Fukuda I, Tatsumi N, Ueda T, Fujiki F, Nomura M, Nishida S, Shirakata T, Hosen N, Tsuboi A, Oka Y, Nezu R, Mori M, Doki Y, Aozasa K, Sugiyama H, Oji Y (2009) Overexpression of eukaryotic elongation factor eEF2 in gastrointestinal cancers and its involvement in G2/M progression in the cell cycle. Int J Oncol 34:1181–1189PubMed
8.
go back to reference Oji Y, Tatsumi N, Fukuda M, Nakatsuka S, Aoyagi S, Hirata E, Nanchi I, Fujiki F, Nakajima H, Yamamoto Y, Shibata S, Nakamru M, Hasegawa K, Takagi S, Fukada I, Hoshikawa T, Murakami Y (2014) The translation elongation factor eEF2 is a novel tumor-associated antigen overexpressed in various types of cancers. Int J Oncol 44:1461–1469CrossRefPubMedPubMedCentral Oji Y, Tatsumi N, Fukuda M, Nakatsuka S, Aoyagi S, Hirata E, Nanchi I, Fujiki F, Nakajima H, Yamamoto Y, Shibata S, Nakamru M, Hasegawa K, Takagi S, Fukada I, Hoshikawa T, Murakami Y (2014) The translation elongation factor eEF2 is a novel tumor-associated antigen overexpressed in various types of cancers. Int J Oncol 44:1461–1469CrossRefPubMedPubMedCentral
9.
go back to reference Sun HG, Dong XJ, Lu T, Yang MF, Wang XM (2014) Clinical value of eukaryotic elongation factor 2 in non-small cell lung cancer patients. Asian Pac J Cancer Prev 14:6533–6535CrossRefPubMed Sun HG, Dong XJ, Lu T, Yang MF, Wang XM (2014) Clinical value of eukaryotic elongation factor 2 in non-small cell lung cancer patients. Asian Pac J Cancer Prev 14:6533–6535CrossRefPubMed
10.
go back to reference Tan HY, Wang N, Tsao SW, Zhang Z, Feng Y (2014) Suppression of vascular endothelial growth factor via inactivation of eukaryotic elongation factor 2 by alkaloids in coptidis rhizome in hepatocellular carcinoma. Integr Cancer Ther 13:425–434CrossRefPubMed Tan HY, Wang N, Tsao SW, Zhang Z, Feng Y (2014) Suppression of vascular endothelial growth factor via inactivation of eukaryotic elongation factor 2 by alkaloids in coptidis rhizome in hepatocellular carcinoma. Integr Cancer Ther 13:425–434CrossRefPubMed
11.
12.
go back to reference Anand N, Murthy S, Amann G, Wernick M, Porter LA, Cukier IH, Collins C, Gray JW, Diebold J, Demetrick DJ, Lee JM (2002) Protein elongation factor eEF1A2 is a putative oncogene in ovarian cancer. Nat Genet 31:301–305CrossRefPubMed Anand N, Murthy S, Amann G, Wernick M, Porter LA, Cukier IH, Collins C, Gray JW, Diebold J, Demetrick DJ, Lee JM (2002) Protein elongation factor eEF1A2 is a putative oncogene in ovarian cancer. Nat Genet 31:301–305CrossRefPubMed
13.
go back to reference Yoshizawa A, Fukuoka J, Shimizu S, Shimizu S, Shilo K, Franks TJ, Hewitt SM, Fujii T, Cordon-cardo C, Jen J, Travis WD (2010) Overexpression of phosphor-eIF4E is associated with survival through AKT pathway in on-small cell lung cancer. Clin Cancer Res 16:240–248CrossRefPubMed Yoshizawa A, Fukuoka J, Shimizu S, Shimizu S, Shilo K, Franks TJ, Hewitt SM, Fujii T, Cordon-cardo C, Jen J, Travis WD (2010) Overexpression of phosphor-eIF4E is associated with survival through AKT pathway in on-small cell lung cancer. Clin Cancer Res 16:240–248CrossRefPubMed
14.
go back to reference Pinke DE, Kalloger SE, Francetic T, Huntsman DG, Lee JM (2008) The prognostic significance of elongation factor eEF1A2 on ovarian cancer. Gynecol Oncol 108:561–568CrossRefPubMed Pinke DE, Kalloger SE, Francetic T, Huntsman DG, Lee JM (2008) The prognostic significance of elongation factor eEF1A2 on ovarian cancer. Gynecol Oncol 108:561–568CrossRefPubMed
15.
go back to reference Hagner PR, Schneider A, Gartenhaus RB (2010) Targeting the translational machinery as a novel treatment strategy for hematologic malignancies. Blood 115:2127–2135CrossRefPubMedPubMedCentral Hagner PR, Schneider A, Gartenhaus RB (2010) Targeting the translational machinery as a novel treatment strategy for hematologic malignancies. Blood 115:2127–2135CrossRefPubMedPubMedCentral
16.
go back to reference Chen CY, Fang HY, Chiou SH, Yi SE, Huang CY, Chiang SF, Chang HW, Lin TY, Chiang IP, Chow KC (2011) Sumoylation of eukaryotic elongation factor 2 is vital for protein stability and anti-apoptotic activity in lung adenocarcinoma cells. Cancer Sci 102:1582–1589CrossRefPubMed Chen CY, Fang HY, Chiou SH, Yi SE, Huang CY, Chiang SF, Chang HW, Lin TY, Chiang IP, Chow KC (2011) Sumoylation of eukaryotic elongation factor 2 is vital for protein stability and anti-apoptotic activity in lung adenocarcinoma cells. Cancer Sci 102:1582–1589CrossRefPubMed
17.
go back to reference Bilanges B, Stokoe D (2007) Mechanisms of translational deregulation in human tumors and therapeutic intervention strategies. Oncogene 26:5973–5970CrossRefPubMed Bilanges B, Stokoe D (2007) Mechanisms of translational deregulation in human tumors and therapeutic intervention strategies. Oncogene 26:5973–5970CrossRefPubMed
18.
go back to reference Wang N, Feng YB, Tan HY, Cheung F, Hong M, Lao L, Nagamatsu T (2015) Inhibition of eukaryotic elongation factor-2 confers to tumor suppression by a herbal formulation huanglian-jiedu decoction in human hepatocellular carcinoma. J Ethnopharmacol 164:309–318CrossRefPubMed Wang N, Feng YB, Tan HY, Cheung F, Hong M, Lao L, Nagamatsu T (2015) Inhibition of eukaryotic elongation factor-2 confers to tumor suppression by a herbal formulation huanglian-jiedu decoction in human hepatocellular carcinoma. J Ethnopharmacol 164:309–318CrossRefPubMed
19.
go back to reference Nowroozi MR, Momeni SA, Ohadian Moghadam S, Ayati E, Mortazavi A, Arfae S, Jamshidian H, Taherimahmoudi M, Ayati M (2016) Prostate-specific antigen density and Gleason score predict adverse pathologic features in patients with clinically localized prostate cancer. Nephrourol Mon 8:39984–39987 Nowroozi MR, Momeni SA, Ohadian Moghadam S, Ayati E, Mortazavi A, Arfae S, Jamshidian H, Taherimahmoudi M, Ayati M (2016) Prostate-specific antigen density and Gleason score predict adverse pathologic features in patients with clinically localized prostate cancer. Nephrourol Mon 8:39984–39987
20.
go back to reference Kgatle MM, Kalla AA, Islam MM, Sathekge M, Moorad R (2016) Prostate cancer: epigenetic alterations, risk factors, and therapy. Prostate Cancer 6:435–445 Kgatle MM, Kalla AA, Islam MM, Sathekge M, Moorad R (2016) Prostate cancer: epigenetic alterations, risk factors, and therapy. Prostate Cancer 6:435–445
Metadata
Title
Eukaryotic Elongation Factor 2 (eEF2) is a Potential Biomarker of Prostate Cancer
Authors
Xuefeng Zhang
Linkun Hu
Mingzhan Du
Xuedong Wei
Jun Zhang
Yu Hui
Cheng Chen
Gang Li
Jianquan Hou
Publication date
01-10-2018
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 4/2018
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-017-0302-7

Other articles of this Issue 4/2018

Pathology & Oncology Research 4/2018 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine