Skip to main content
Erschienen in: Medical Oncology 9/2014

01.09.2014 | Original Paper

The prognostic value of Cyclin B1 in pancreatic cancer

verfasst von: Li Zhou, Jian Li, Yu-Pei Zhao, Quan-Cai Cui, Wei-Xun Zhou, Jun-Chao Guo, Lei You, Wen-Ming Wu, Tai-Ping Zhang

Erschienen in: Medical Oncology | Ausgabe 9/2014

Einloggen, um Zugang zu erhalten

Abstract

Pancreatic cancer (PC), a malignancy with very poor prognosis, presents many molecular alterations, including overexpression of Cyclin B1. However, the prognostic value of the protein in PC remains to be elucidated. In the present study, Cyclin B1 expression was detected immunohistochemically in specimens from 241 patients with PC and was correlated with clinicopathological features and patient survival. It was found that Cyclin B1 expression, located in nucleus and/or cytoplasm, was not statistically associated with clinicopathologic variables. However, overall survival of patients with high Cyclin B1 expression was significantly poorer than that of those with low Cyclin B1 expression (P = 0.010). Moreover, Cyclin B1 was identified as an independent prognostic factor by multivariate Cox regression test (P = 0.003). Finally, its independent implication for prognosis was proven in five subgroups of PC, i.e., males, patients aged ≤65 years, G1–2 and N0 tumors as well as those with perineural invasion (all P < 0.05). These data indicate that high expression of Cyclin B1 is a valuable molecular marker of unfavorable prognosis in PC.
Literatur
2.
Zurück zum Zitat Lee SR, Kim HO, Son BH, Yoo CH, Shin JH. Prognostic factors associated with long-term survival and recurrence in pancreatic adenocarcinoma. Hepatogastroenterology. 2013;60(122):358–62.PubMed Lee SR, Kim HO, Son BH, Yoo CH, Shin JH. Prognostic factors associated with long-term survival and recurrence in pancreatic adenocarcinoma. Hepatogastroenterology. 2013;60(122):358–62.PubMed
3.
Zurück zum Zitat Strasberg SM, Gao F, Sanford D, Linehan DC, Hawkins WG, Fields R, et al. Jaundice: an important, poorly recognized risk factor for diminished survival in patients with adenocarcinoma of the head of the pancreas. HPB (Oxford). 2014;16(2):150–6.PubMedCrossRef Strasberg SM, Gao F, Sanford D, Linehan DC, Hawkins WG, Fields R, et al. Jaundice: an important, poorly recognized risk factor for diminished survival in patients with adenocarcinoma of the head of the pancreas. HPB (Oxford). 2014;16(2):150–6.PubMedCrossRef
4.
Zurück zum Zitat Zhang JF, Hua R, Sun YW, Liu W, Huo YM, Liu DJ, et al. Influence of perineural invasion on survival and recurrence in patients with resected pancreatic cancer. Asian Pac J Cancer Prev. 2013;14(9):5133–9.PubMedCrossRef Zhang JF, Hua R, Sun YW, Liu W, Huo YM, Liu DJ, et al. Influence of perineural invasion on survival and recurrence in patients with resected pancreatic cancer. Asian Pac J Cancer Prev. 2013;14(9):5133–9.PubMedCrossRef
5.
Zurück zum Zitat Szkandera J, Stotz M, Absenger G, Stojakovic T, Samonigg H, Kornprat P, et al. Validation of C-reactive protein levels as a prognostic indicator for survival in a large cohort of pancreatic cancer patients. Br J Cancer. 2014;110(1):183–8.PubMedCrossRef Szkandera J, Stotz M, Absenger G, Stojakovic T, Samonigg H, Kornprat P, et al. Validation of C-reactive protein levels as a prognostic indicator for survival in a large cohort of pancreatic cancer patients. Br J Cancer. 2014;110(1):183–8.PubMedCrossRef
6.
Zurück zum Zitat Distler M, Pilarsky E, Kersting S, Grützmann R. Preoperative CEA and CA 19-9 are prognostic markers for survival after curative resection for ductal adenocarcinoma of the pancreas - a retrospective tumor marker prognostic study. Int J Surg. 2013;11(10):1067–72.PubMedCrossRef Distler M, Pilarsky E, Kersting S, Grützmann R. Preoperative CEA and CA 19-9 are prognostic markers for survival after curative resection for ductal adenocarcinoma of the pancreas - a retrospective tumor marker prognostic study. Int J Surg. 2013;11(10):1067–72.PubMedCrossRef
7.
Zurück zum Zitat Oshima M, Okano K, Muraki S, Haba R, Maeba T, Suzuki Y, et al. Immunohistochemically detected expression of 3 major genes (CDKN2A/p16, TP53, and SMAD4/DPC4) strongly predicts survival in patients with resectable pancreatic cancer. Ann Surg. 2013;258(2):336–46.PubMedCrossRef Oshima M, Okano K, Muraki S, Haba R, Maeba T, Suzuki Y, et al. Immunohistochemically detected expression of 3 major genes (CDKN2A/p16, TP53, and SMAD4/DPC4) strongly predicts survival in patients with resectable pancreatic cancer. Ann Surg. 2013;258(2):336–46.PubMedCrossRef
8.
Zurück zum Zitat Milatovich A, Francke U. Human cyclin B1 gene (CCNB1) assigned to chromosome 5 (q13-qter). Somat Cell Mol Genet. 1992;18(3):303–7.PubMedCrossRef Milatovich A, Francke U. Human cyclin B1 gene (CCNB1) assigned to chromosome 5 (q13-qter). Somat Cell Mol Genet. 1992;18(3):303–7.PubMedCrossRef
9.
Zurück zum Zitat Gomez LA, de Las Pozas A, Reiner T, Burnstein K, Perez-Stable C. Increased expression of cyclin B1 sensitizes prostate cancer cells to apoptosis induced by chemotherapy. Mol Cancer Ther. 2007;6(5):1534–43.PubMedCrossRef Gomez LA, de Las Pozas A, Reiner T, Burnstein K, Perez-Stable C. Increased expression of cyclin B1 sensitizes prostate cancer cells to apoptosis induced by chemotherapy. Mol Cancer Ther. 2007;6(5):1534–43.PubMedCrossRef
10.
Zurück zum Zitat Song Y, Zhao C, Dong L, Fu M, Xue L, Huang Z, et al. Overexpression of cyclin B1 in human esophageal squamous cell carcinoma cells induces tumor cell invasive growth and metastasis. Carcinogenesis. 2008;29(2):307–15.PubMedCrossRef Song Y, Zhao C, Dong L, Fu M, Xue L, Huang Z, et al. Overexpression of cyclin B1 in human esophageal squamous cell carcinoma cells induces tumor cell invasive growth and metastasis. Carcinogenesis. 2008;29(2):307–15.PubMedCrossRef
11.
Zurück zum Zitat Matthess Y, Raab M, Sanhaji M, Lavrik IN, Strebhardt K. Cdk1/cyclin B1 controls Fas-mediated apoptosis by regulating caspase-8 activity. Mol Cell Biol. 2010;30(24):5726–40.PubMedCrossRefPubMedCentral Matthess Y, Raab M, Sanhaji M, Lavrik IN, Strebhardt K. Cdk1/cyclin B1 controls Fas-mediated apoptosis by regulating caspase-8 activity. Mol Cell Biol. 2010;30(24):5726–40.PubMedCrossRefPubMedCentral
12.
Zurück zum Zitat Bonnet ME, Gossart JB, Benoit E, Messmer M, Zounib O, Moreau V, et al. Systemic delivery of sticky siRNAs targeting the cell cycle for lung tumor metastasis inhibition. J Control Release. 2013;170(2):183–90.PubMedCrossRef Bonnet ME, Gossart JB, Benoit E, Messmer M, Zounib O, Moreau V, et al. Systemic delivery of sticky siRNAs targeting the cell cycle for lung tumor metastasis inhibition. J Control Release. 2013;170(2):183–90.PubMedCrossRef
13.
Zurück zum Zitat Kedinger V, Meulle A, Zounib O, Bonnet ME, Gossart JB, Benoit E, et al. Sticky siRNAs targeting survivin and cyclin B1 exert an antitumoral effect on melanoma subcutaneous xenografts and lung metastases. BMC Cancer. 2013;13:338.PubMedCrossRefPubMedCentral Kedinger V, Meulle A, Zounib O, Bonnet ME, Gossart JB, Benoit E, et al. Sticky siRNAs targeting survivin and cyclin B1 exert an antitumoral effect on melanoma subcutaneous xenografts and lung metastases. BMC Cancer. 2013;13:338.PubMedCrossRefPubMedCentral
14.
Zurück zum Zitat Nozoe T, Korenaga D, Kabashima A, Ohga T, Saeki H, Sugimachi K. Significance of cyclin B1 expression as an independent prognostic indicator of patients with squamous cell carcinoma of the esophagus. Clin Cancer Res. 2002;8(3):817–22.PubMed Nozoe T, Korenaga D, Kabashima A, Ohga T, Saeki H, Sugimachi K. Significance of cyclin B1 expression as an independent prognostic indicator of patients with squamous cell carcinoma of the esophagus. Clin Cancer Res. 2002;8(3):817–22.PubMed
15.
Zurück zum Zitat Arinaga M, Noguchi T, Takeno S, Chujo M, Miura T, Kimura Y, et al. Clinical implication of cyclin B1 in non-small cell lung cancer. Oncol Rep. 2003;10(5):1381–6.PubMed Arinaga M, Noguchi T, Takeno S, Chujo M, Miura T, Kimura Y, et al. Clinical implication of cyclin B1 in non-small cell lung cancer. Oncol Rep. 2003;10(5):1381–6.PubMed
16.
Zurück zum Zitat Aaltonen K, Amini RM, Heikkilä P, Aittomäki K, Tamminen A, Nevanlinna H, et al. High cyclin B1 expression is associated with poor survival in breast cancer. Br J Cancer. 2009;100(7):1055–60.PubMedCrossRefPubMedCentral Aaltonen K, Amini RM, Heikkilä P, Aittomäki K, Tamminen A, Nevanlinna H, et al. High cyclin B1 expression is associated with poor survival in breast cancer. Br J Cancer. 2009;100(7):1055–60.PubMedCrossRefPubMedCentral
17.
Zurück zum Zitat Begnami MD, Fregnani JH, Nonogaki S, Soares FA. Evaluation of cell cycle protein expression in gastric cancer: cyclin B1 expression and its prognostic implication. Hum Pathol. 2010;41(8):1120–7.PubMedCrossRef Begnami MD, Fregnani JH, Nonogaki S, Soares FA. Evaluation of cell cycle protein expression in gastric cancer: cyclin B1 expression and its prognostic implication. Hum Pathol. 2010;41(8):1120–7.PubMedCrossRef
18.
Zurück zum Zitat Grabsch H, Lickvers K, Hansen O, Takeno S, Willers R, Stock W, et al. Prognostic value of cyclin B1 protein expression in colorectal cancer. Am J Clin Pathol. 2004;122(4):511–6.PubMedCrossRef Grabsch H, Lickvers K, Hansen O, Takeno S, Willers R, Stock W, et al. Prognostic value of cyclin B1 protein expression in colorectal cancer. Am J Clin Pathol. 2004;122(4):511–6.PubMedCrossRef
19.
Zurück zum Zitat Björck E, Ek S, Landgren O, Jerkeman M, Ehinger M, Björkholm M, et al. High expression of cyclin B1 predicts a favorable outcome in patients with follicular lymphoma. Blood. 2005;105(7):2908–15.PubMedCrossRef Björck E, Ek S, Landgren O, Jerkeman M, Ehinger M, Björkholm M, et al. High expression of cyclin B1 predicts a favorable outcome in patients with follicular lymphoma. Blood. 2005;105(7):2908–15.PubMedCrossRef
20.
Zurück zum Zitat Shin JU, Lee CH, Lee KT, Lee JK, Lee KH, Kim KM, et al. Prognostic significance of ATM and cyclin B1 in pancreatic neuroendocrine tumor. Tumour Biol. 2012;33(5):1645–51.PubMedCrossRef Shin JU, Lee CH, Lee KT, Lee JK, Lee KH, Kim KM, et al. Prognostic significance of ATM and cyclin B1 in pancreatic neuroendocrine tumor. Tumour Biol. 2012;33(5):1645–51.PubMedCrossRef
21.
Zurück zum Zitat Ito Y, Takeda T, Wakasa K, Tsujimoto M, Okada M, Matsuura N. Expression of the G2-M modulators in pancreatic adenocarcinoma. Pancreatology. 2002;2(2):138–45.PubMedCrossRef Ito Y, Takeda T, Wakasa K, Tsujimoto M, Okada M, Matsuura N. Expression of the G2-M modulators in pancreatic adenocarcinoma. Pancreatology. 2002;2(2):138–45.PubMedCrossRef
22.
Zurück zum Zitat Kamio Y, Maeda K, Moriya T, Takasu N, Takeshita A, Hirai I, et al. Clinicopathological significance of cell cycle regulatory factors and differentiation-related factors in pancreatic neoplasms. Pancreas. 2010;39(3):345–52.PubMedCrossRef Kamio Y, Maeda K, Moriya T, Takasu N, Takeshita A, Hirai I, et al. Clinicopathological significance of cell cycle regulatory factors and differentiation-related factors in pancreatic neoplasms. Pancreas. 2010;39(3):345–52.PubMedCrossRef
23.
Zurück zum Zitat Guo JC, Li J, Yang YC, Zhou L, Zhang TP, Zhao YP. Oligonucleotide microarray identifies genes differentially expressed during tumorigenesis of DMBA-induced pancreatic cancer in rats. PLoS One. 2013;8(12):e82910.PubMedCrossRefPubMedCentral Guo JC, Li J, Yang YC, Zhou L, Zhang TP, Zhao YP. Oligonucleotide microarray identifies genes differentially expressed during tumorigenesis of DMBA-induced pancreatic cancer in rats. PLoS One. 2013;8(12):e82910.PubMedCrossRefPubMedCentral
24.
Zurück zum Zitat Guo JC, Li J, Zhao YP, Zhou L, Cui QC, Zhou WX, et al. N-WASP in pancreatic ductal adenocarcinoma: associations with peri-neural invasion and poor prognosis. World J Surg. 2014;38(8):2126-31. Guo JC, Li J, Zhao YP, Zhou L, Cui QC, Zhou WX, et al. N-WASP in pancreatic ductal adenocarcinoma: associations with peri-neural invasion and poor prognosis. World J Surg. 2014;38(8):2126-31.
25.
Zurück zum Zitat Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.PubMedCrossRef Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.PubMedCrossRef
26.
Zurück zum Zitat Musgrove EA. Cyclins: roles in mitogenic signaling and oncogenic transformation. Growth Factors. 2006;24(1):13–9.PubMedCrossRef Musgrove EA. Cyclins: roles in mitogenic signaling and oncogenic transformation. Growth Factors. 2006;24(1):13–9.PubMedCrossRef
27.
Zurück zum Zitat Castedo M, Perfettini JL, Roumier T, Kroemer G. Cyclin-dependent kinase-1: linking apoptosis to cell cycle and mitotic catastrophe. Cell Death Differ. 2002;9(12):1287–93.PubMedCrossRef Castedo M, Perfettini JL, Roumier T, Kroemer G. Cyclin-dependent kinase-1: linking apoptosis to cell cycle and mitotic catastrophe. Cell Death Differ. 2002;9(12):1287–93.PubMedCrossRef
28.
Zurück zum Zitat Ansari D, Rosendahl A, Elebro J, Andersson R. Systematic review of immunohistochemical biomarkers to identify prognostic subgroups of patients with pancreatic cancer. Br J Surg. 2011;98(8):1041–55.PubMedCrossRef Ansari D, Rosendahl A, Elebro J, Andersson R. Systematic review of immunohistochemical biomarkers to identify prognostic subgroups of patients with pancreatic cancer. Br J Surg. 2011;98(8):1041–55.PubMedCrossRef
29.
Zurück zum Zitat Winter JM, Yeo CJ, Brody JR. Diagnostic, prognostic, and predictive biomarkers in pancreatic cancer. J Surg Oncol. 2013;107(1):15–22.PubMedCrossRef Winter JM, Yeo CJ, Brody JR. Diagnostic, prognostic, and predictive biomarkers in pancreatic cancer. J Surg Oncol. 2013;107(1):15–22.PubMedCrossRef
Metadaten
Titel
The prognostic value of Cyclin B1 in pancreatic cancer
verfasst von
Li Zhou
Jian Li
Yu-Pei Zhao
Quan-Cai Cui
Wei-Xun Zhou
Jun-Chao Guo
Lei You
Wen-Ming Wu
Tai-Ping Zhang
Publikationsdatum
01.09.2014
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 9/2014
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0107-4

Weitere Artikel der Ausgabe 9/2014

Medical Oncology 9/2014 Zur Ausgabe

Update Onkologie

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