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Erschienen in: Clinical and Translational Oncology 2/2014

01.02.2014 | Research Article

PKM2 and ACVR 1C are prognostic markers for poor prognosis of gallbladder cancer

verfasst von: J. Li, Z. Yang, Q. Zou, Y. Yuan, J. Li, L. Liang, G. Zeng, S. Chen

Erschienen in: Clinical and Translational Oncology | Ausgabe 2/2014

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Abstract

Purpose

To identify biological markers related to the progression and prognosis of GBC.

Methods

The expressions of pyruvate kinase isoenzyme type M2 (PKM2) and activin A receptor type IC (ACVR 1C) in 46 squamous cell/adenosquamous carcinomas (SC/ASC) and 80 adenocarcinomas (AC) were examined using immunohistochemistry.

Results

Positive PKM2 and negative ACVR 1C expressions were significantly associated with lymph node metastasis, invasion and TNM stage of SC/ASCs and ACs. Univariate Kaplan–Meier analysis showed that either elevated PKM2 or loss of ACVR 1C expression significantly correlated with shorter average survival times in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that positive PKM2 expression and loss of ACVR 1C expression were poor prognosis biomarkers in both SC/ASC and AC patients.

Conclusions

Our study suggested that PKM2 overexpression is a marker of metastasis, invasion and poor prognosis of GBC. ACVR 1C is a tumor suppressor, and lowered ACVR 1C expression is an important marker for the metastasis, invasion, and prognosis of GBC.
Literatur
1.
Zurück zum Zitat Jayaraman S, Jarnagin WR. Management of gallbladder cancer. Gastroenterol Clin North Am. 2010;39:331–42.PubMedCrossRef Jayaraman S, Jarnagin WR. Management of gallbladder cancer. Gastroenterol Clin North Am. 2010;39:331–42.PubMedCrossRef
2.
Zurück zum Zitat Hawkins WG, DeMatteo RP, Jarnagin WR, Ben-Porat L, Blumgart LH, Fong Y. Jaundice predicts advanced disease and early mortality in patients with gallbladder cancer. Ann Surg Oncol. 2004;11:310–5.PubMedCrossRef Hawkins WG, DeMatteo RP, Jarnagin WR, Ben-Porat L, Blumgart LH, Fong Y. Jaundice predicts advanced disease and early mortality in patients with gallbladder cancer. Ann Surg Oncol. 2004;11:310–5.PubMedCrossRef
3.
Zurück zum Zitat de Aretxabala X, Roa I, Burgos L, Losada H, Roa JC, Mora J, et al. Gallbladder cancer: an analysis of a series of 139 patients with restricted to the subserosal layer. J Gastrointest Surg. 2006;10:186–92.PubMedCrossRef de Aretxabala X, Roa I, Burgos L, Losada H, Roa JC, Mora J, et al. Gallbladder cancer: an analysis of a series of 139 patients with restricted to the subserosal layer. J Gastrointest Surg. 2006;10:186–92.PubMedCrossRef
4.
Zurück zum Zitat Ootani T, Shirai Y, Tsukada K, Muto T. Relationship between gallbladder carcinoma and the segmental type of adenomyomatosis of the gallbladder. Cancer. 1992;69:2647–52.PubMedCrossRef Ootani T, Shirai Y, Tsukada K, Muto T. Relationship between gallbladder carcinoma and the segmental type of adenomyomatosis of the gallbladder. Cancer. 1992;69:2647–52.PubMedCrossRef
5.
Zurück zum Zitat Roa JC, Tapia O, Cakir A, Basturk O, Dursun N, Akdemir D, et al. Squamous cell and adenosquamous carcinomas of the gallbladder: clinicopathological analysis of 34 cases identified in 606 carcinomas. Mod Pathol. 2011;24:1069–78.PubMedCrossRef Roa JC, Tapia O, Cakir A, Basturk O, Dursun N, Akdemir D, et al. Squamous cell and adenosquamous carcinomas of the gallbladder: clinicopathological analysis of 34 cases identified in 606 carcinomas. Mod Pathol. 2011;24:1069–78.PubMedCrossRef
6.
Zurück zum Zitat Mazurek S. Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells. Int J Biochem Cell Biol. 2011;43:969–80.PubMedCrossRef Mazurek S. Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells. Int J Biochem Cell Biol. 2011;43:969–80.PubMedCrossRef
7.
Zurück zum Zitat Mazurek S, Boschek CB, Hugo F, Eigenbrodt E. Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin Cancer Biol. 2005;15:300–8.PubMedCrossRef Mazurek S, Boschek CB, Hugo F, Eigenbrodt E. Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin Cancer Biol. 2005;15:300–8.PubMedCrossRef
8.
Zurück zum Zitat Spoden GA, Mazurek S, Morandell D, Bacher N, Ausserlechner MJ, Jansen-Dürr P, et al. Isotype-specific inhibitors of the glycolytic key regulator pyruvate kinase subtype M2 moderately decelerate tumor cell proliferation. Int J Cancer. 2008;123:312–21.PubMedCrossRef Spoden GA, Mazurek S, Morandell D, Bacher N, Ausserlechner MJ, Jansen-Dürr P, et al. Isotype-specific inhibitors of the glycolytic key regulator pyruvate kinase subtype M2 moderately decelerate tumor cell proliferation. Int J Cancer. 2008;123:312–21.PubMedCrossRef
9.
Zurück zum Zitat Jiang K, He B, Lai L, Chen Q, Liu Y, Guo Q, et al. Cyclosporine A inhibits breast cancer cell growth by downregulating the expression of pyruvate kinase subtype M2. Int J Mol Med. 2012;30:302–8.PubMed Jiang K, He B, Lai L, Chen Q, Liu Y, Guo Q, et al. Cyclosporine A inhibits breast cancer cell growth by downregulating the expression of pyruvate kinase subtype M2. Int J Mol Med. 2012;30:302–8.PubMed
10.
11.
Zurück zum Zitat Tsuchida K, Nakatani M, Uezumi A, Murakami T, Cui X. Signal transduction pathway through activin receptors as a therapeutic target of musculoskeletal diseases and cancer. Endocr J. 2008;55:11–21.PubMedCrossRef Tsuchida K, Nakatani M, Uezumi A, Murakami T, Cui X. Signal transduction pathway through activin receptors as a therapeutic target of musculoskeletal diseases and cancer. Endocr J. 2008;55:11–21.PubMedCrossRef
12.
Zurück zum Zitat Angenete E, Langenskiöld M, Palmgren I, Falk P, Oresland T, Ivarsson ML. Transforming growth factor beta-1 in rectal tumor, mucosa and plasma in relation to radiotherapy and clinical outcome in rectal cancer patients. Int J Colorectal Dis. 2007;22:1331–8.PubMedCrossRef Angenete E, Langenskiöld M, Palmgren I, Falk P, Oresland T, Ivarsson ML. Transforming growth factor beta-1 in rectal tumor, mucosa and plasma in relation to radiotherapy and clinical outcome in rectal cancer patients. Int J Colorectal Dis. 2007;22:1331–8.PubMedCrossRef
13.
Zurück zum Zitat Joshi A, Cao D. TGF-beta signaling, tumor microenvironment and tumor progression: the butterfly effect. Front Biosci. 2010;15:180–94.CrossRef Joshi A, Cao D. TGF-beta signaling, tumor microenvironment and tumor progression: the butterfly effect. Front Biosci. 2010;15:180–94.CrossRef
14.
Zurück zum Zitat Liu DC, Yang ZL, Jiang S. Identification of PEG10 and TSG101 as carcinogenesis, progression, and poor-prognosis related biomarkers for gallbladder adenocarcinoma. Pathol Oncol Res. 2011;17:859–66.PubMedCrossRef Liu DC, Yang ZL, Jiang S. Identification of PEG10 and TSG101 as carcinogenesis, progression, and poor-prognosis related biomarkers for gallbladder adenocarcinoma. Pathol Oncol Res. 2011;17:859–66.PubMedCrossRef
15.
Zurück zum Zitat Kondo M, Dono K, Sakon M, Shimizu J, Nagano H, Nakamori S, et al. Adenosquamous carcinoma of the gallbladder. Hepatogastroenterology. 2002;49:1230–4.PubMed Kondo M, Dono K, Sakon M, Shimizu J, Nagano H, Nakamori S, et al. Adenosquamous carcinoma of the gallbladder. Hepatogastroenterology. 2002;49:1230–4.PubMed
16.
Zurück zum Zitat Mazurek S. Pyruvate kinase type M2: a key regulator within the tumour metabolome and a tool for metabolic profiling of tumours. Ernst Schering Found Symp Proc. 2007;4:99–124.PubMed Mazurek S. Pyruvate kinase type M2: a key regulator within the tumour metabolome and a tool for metabolic profiling of tumours. Ernst Schering Found Symp Proc. 2007;4:99–124.PubMed
17.
Zurück zum Zitat Hoda MA, Münzker J, Ghanim B, Schelch K, Klikovits T, Laszlo V, et al. Suppression of activin A signals inhibits growth of malignant pleural mesothelioma cells. Br J Cancer. 2012;107:1978–86.PubMedCentralPubMedCrossRef Hoda MA, Münzker J, Ghanim B, Schelch K, Klikovits T, Laszlo V, et al. Suppression of activin A signals inhibits growth of malignant pleural mesothelioma cells. Br J Cancer. 2012;107:1978–86.PubMedCentralPubMedCrossRef
Metadaten
Titel
PKM2 and ACVR 1C are prognostic markers for poor prognosis of gallbladder cancer
verfasst von
J. Li
Z. Yang
Q. Zou
Y. Yuan
J. Li
L. Liang
G. Zeng
S. Chen
Publikationsdatum
01.02.2014
Verlag
Springer Milan
Erschienen in
Clinical and Translational Oncology / Ausgabe 2/2014
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-013-1063-8

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