Skip to main content
Top
Published in: Journal of Translational Medicine 1/2009

Open Access 01-12-2009 | Research

Survivin gene levels in the peripheral blood of patients with gastric cancer independently predict survival

Authors: Loris Bertazza, Simone Mocellin, Alberto Marchet, Pierluigi Pilati, Joseph Gabrieli, Romano Scalerta, Donato Nitti

Published in: Journal of Translational Medicine | Issue 1/2009

Login to get access

Abstract

Background

The detection of circulating tumor cells (CTC) is considered a promising tool for improving risk stratification in patients with solid tumors. We investigated on whether the expression of CTC related genes adds any prognostic power to the TNM staging system in patients with gastric carcinoma.

Methods

Seventy patients with TNM stage I to IV gastric carcinoma were retrospectively enrolled. Peripheral blood samples were tested by means of quantitative real time PCR (qrtPCR) for the expression of four CTC related genes: carcinoembryonic antigen (CEA), cytokeratin-19 (CK19), vascular endothelial growth factor (VEGF) and Survivin (BIRC5).

Results

Gene expression of Survivin, CK19, CEA and VEGF was higher than in normal controls in 98.6%, 97.1%, 42.9% and 38.6% of cases, respectively, suggesting a potential diagnostic value of both Survivin and CK19. At multivariable survival analysis, TNM staging and Survivin mRNA levels were retained as independent prognostic factors, demonstrating that Survivin expression in the peripheral blood adds prognostic information to the TNM system. In contrast with previously published data, the transcript abundance of CEA, CK19 and VEGF was not associated with patients' clinical outcome.

Conclusions

Gene expression levels of Survivin add significant prognostic value to the current TNM staging system. The validation of these findings in larger prospective and multicentric series might lead to the implementation of this biomarker in the routine clinical setting in order to optimize risk stratification and ultimately personalize the therapeutic management of these patients.
Appendix
Available only for authorised users
Literature
1.
go back to reference de Vries AC, Meijer GA, Looman CW, Casparie MK, Hansen BE, van Grieken NC, Kuipers EJ: Epidemiological trends of pre-malignant gastric lesions: a long-term nationwide study in the Netherlands. Gut. 2007, 56: 1665-1670. 10.1136/gut.2007.127167.PubMedCentralCrossRefPubMed de Vries AC, Meijer GA, Looman CW, Casparie MK, Hansen BE, van Grieken NC, Kuipers EJ: Epidemiological trends of pre-malignant gastric lesions: a long-term nationwide study in the Netherlands. Gut. 2007, 56: 1665-1670. 10.1136/gut.2007.127167.PubMedCentralCrossRefPubMed
2.
go back to reference Greene FL, Sobin LH: The TNM system: our language for cancer care. J Surg Oncol. 2002, 80: 119-120. 10.1002/jso.10114.CrossRefPubMed Greene FL, Sobin LH: The TNM system: our language for cancer care. J Surg Oncol. 2002, 80: 119-120. 10.1002/jso.10114.CrossRefPubMed
3.
go back to reference Aurello P, D'Angelo F, Rossi S, Bellagamba R, Cicchini C, Nigri G, Ercolani G, De Angelis R, Ramacciato G: Classification of lymph node metastases from gastric cancer: comparison between N-site and N-number systems. Our experience and review of the literature. Am Surg. 2007, 73: 359-366.PubMed Aurello P, D'Angelo F, Rossi S, Bellagamba R, Cicchini C, Nigri G, Ercolani G, De Angelis R, Ramacciato G: Classification of lymph node metastases from gastric cancer: comparison between N-site and N-number systems. Our experience and review of the literature. Am Surg. 2007, 73: 359-366.PubMed
4.
go back to reference Goldberg RM, Fleming TR, Tangen CM, Moertel CG, Macdonald JS, Haller DG, Laurie JA: Surgery for recurrent colon cancer: strategies for identifying resectable recurrence and success rates after resection. Eastern Cooperative Oncology Group, the North Central Cancer Treatment Group, and the Southwest Oncology Group. Ann Intern Med. 1998, 129: 27-35.CrossRefPubMed Goldberg RM, Fleming TR, Tangen CM, Moertel CG, Macdonald JS, Haller DG, Laurie JA: Surgery for recurrent colon cancer: strategies for identifying resectable recurrence and success rates after resection. Eastern Cooperative Oncology Group, the North Central Cancer Treatment Group, and the Southwest Oncology Group. Ann Intern Med. 1998, 129: 27-35.CrossRefPubMed
5.
go back to reference Marrelli D, De Stefano A, de Manzoni G, Morgagni P, Di Leo A, Roviello F: Prediction of recurrence after radical surgery for gastric cancer: a scoring system obtained from a prospective multicenter study. Ann Surg. 2005, 241: 247-255. 10.1097/01.sla.0000152019.14741.97.PubMedCentralCrossRefPubMed Marrelli D, De Stefano A, de Manzoni G, Morgagni P, Di Leo A, Roviello F: Prediction of recurrence after radical surgery for gastric cancer: a scoring system obtained from a prospective multicenter study. Ann Surg. 2005, 241: 247-255. 10.1097/01.sla.0000152019.14741.97.PubMedCentralCrossRefPubMed
6.
go back to reference Janunger KG, Hafstrom L, Glimelius B: Chemotherapy in gastric cancer: a review and updated meta-analysis. Eur J Surg. 2002, 168: 597-608. 10.1080/11024150201680005.CrossRefPubMed Janunger KG, Hafstrom L, Glimelius B: Chemotherapy in gastric cancer: a review and updated meta-analysis. Eur J Surg. 2002, 168: 597-608. 10.1080/11024150201680005.CrossRefPubMed
7.
go back to reference Bertazza L, Mocellin S, Nitti D: Circulating tumor cells in solid cancer: tumor marker of clinical relevance?. Curr Oncol Rep. 2008, 10: 137-146. 10.1007/s11912-008-0022-y.CrossRefPubMed Bertazza L, Mocellin S, Nitti D: Circulating tumor cells in solid cancer: tumor marker of clinical relevance?. Curr Oncol Rep. 2008, 10: 137-146. 10.1007/s11912-008-0022-y.CrossRefPubMed
8.
go back to reference Vogel I, Kalthoff H: Disseminated tumour cells. Their detection and significance for prognosis of gastrointestinal and pancreatic carcinomas. Virchows Arch. 2001, 439: 109-117. 10.1007/s004280100476.CrossRefPubMed Vogel I, Kalthoff H: Disseminated tumour cells. Their detection and significance for prognosis of gastrointestinal and pancreatic carcinomas. Virchows Arch. 2001, 439: 109-117. 10.1007/s004280100476.CrossRefPubMed
9.
go back to reference Koga T, Tokunaga E, Sumiyoshi Y, Oki E, Oda S, Takahashi I, Kakeji Y, Baba H, Maehara Y: Detection of circulating gastric cancer cells in peripheral blood using real time quantitative RT-PCR. Hepatogastroenterology. 2008, 55: 1131-1135.PubMed Koga T, Tokunaga E, Sumiyoshi Y, Oki E, Oda S, Takahashi I, Kakeji Y, Baba H, Maehara Y: Detection of circulating gastric cancer cells in peripheral blood using real time quantitative RT-PCR. Hepatogastroenterology. 2008, 55: 1131-1135.PubMed
10.
go back to reference Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001, 25: 402-408. 10.1006/meth.2001.1262.CrossRefPubMed Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001, 25: 402-408. 10.1006/meth.2001.1262.CrossRefPubMed
11.
go back to reference Mocellin S, Rossi CR, Pilati P, Nitti D, Marincola FM: Quantitative real-time PCR: a powerful ally in cancer research. Trends Mol Med. 2003, 9: 189-195. 10.1016/S1471-4914(03)00047-9.CrossRefPubMed Mocellin S, Rossi CR, Pilati P, Nitti D, Marincola FM: Quantitative real-time PCR: a powerful ally in cancer research. Trends Mol Med. 2003, 9: 189-195. 10.1016/S1471-4914(03)00047-9.CrossRefPubMed
12.
go back to reference Sturzenbaum SR, Kille P: Control genes in quantitative molecular biological techniques: the variability of invariance. Comp Biochem Physiol B Biochem Mol Biol. 2001, 130: 281-289. 10.1016/S1096-4959(01)00440-7.CrossRefPubMed Sturzenbaum SR, Kille P: Control genes in quantitative molecular biological techniques: the variability of invariance. Comp Biochem Physiol B Biochem Mol Biol. 2001, 130: 281-289. 10.1016/S1096-4959(01)00440-7.CrossRefPubMed
14.
go back to reference Altieri DC: Molecular circuits of apoptosis regulation and cell division control: the survivin paradigm. J Cell Biochem. 2004, 92: 656-663. 10.1002/jcb.20140.CrossRefPubMed Altieri DC: Molecular circuits of apoptosis regulation and cell division control: the survivin paradigm. J Cell Biochem. 2004, 92: 656-663. 10.1002/jcb.20140.CrossRefPubMed
15.
go back to reference Yamamoto H, Ngan CY, Monden M: Cancer cells survive with survivin. Cancer Sci. 2008, 99: 1709-1714. 10.1111/j.1349-7006.2008.00870.x.CrossRefPubMed Yamamoto H, Ngan CY, Monden M: Cancer cells survive with survivin. Cancer Sci. 2008, 99: 1709-1714. 10.1111/j.1349-7006.2008.00870.x.CrossRefPubMed
16.
go back to reference Altieri DC: Survivin, cancer networks and pathway-directed drug discovery. Nat Rev Cancer. 2008, 8: 61-70. 10.1038/nrc2293.CrossRefPubMed Altieri DC: Survivin, cancer networks and pathway-directed drug discovery. Nat Rev Cancer. 2008, 8: 61-70. 10.1038/nrc2293.CrossRefPubMed
17.
go back to reference Wang TT, Qian XP, Liu BR: Survivin: potential role in diagnosis, prognosis and targeted therapy of gastric cancer. World J Gastroenterol. 2007, 13: 2784-2790.PubMedCentralPubMed Wang TT, Qian XP, Liu BR: Survivin: potential role in diagnosis, prognosis and targeted therapy of gastric cancer. World J Gastroenterol. 2007, 13: 2784-2790.PubMedCentralPubMed
18.
go back to reference Shen C, Hu L, Xia L, Li Y: The detection of circulating tumor cells of breast cancer patients by using multimarker (Survivin, hTERT and hMAM) quantitative real-time PCR. Clin Biochem. 2009, 42: 194-200. 10.1016/j.clinbiochem.2008.10.016.CrossRefPubMed Shen C, Hu L, Xia L, Li Y: The detection of circulating tumor cells of breast cancer patients by using multimarker (Survivin, hTERT and hMAM) quantitative real-time PCR. Clin Biochem. 2009, 42: 194-200. 10.1016/j.clinbiochem.2008.10.016.CrossRefPubMed
19.
go back to reference Yie SM, Lou B, Ye SR, He X, Cao M, Xie K, Ye NY, Lin R, Wu SM, Xiao HB, Gao E: Clinical significance of detecting survivin-expressing circulating cancer cells in patients with non-small cell lung cancer. Lung Cancer. 2009, 63: 284-290. 10.1016/j.lungcan.2008.05.024.CrossRefPubMed Yie SM, Lou B, Ye SR, He X, Cao M, Xie K, Ye NY, Lin R, Wu SM, Xiao HB, Gao E: Clinical significance of detecting survivin-expressing circulating cancer cells in patients with non-small cell lung cancer. Lung Cancer. 2009, 63: 284-290. 10.1016/j.lungcan.2008.05.024.CrossRefPubMed
20.
go back to reference Yie SM, Lou B, Ye SR, Cao M, He X, Li P, Hu K, Rao L, Wu SM, Xiao HB, Gao E: Detection of survivin-expressing circulating cancer cells (CCCs) in peripheral blood of patients with gastric and colorectal cancer reveals high risks of relapse. Ann Surg Oncol. 2008, 15: 3073-3082. 10.1245/s10434-008-0069-x.CrossRefPubMed Yie SM, Lou B, Ye SR, Cao M, He X, Li P, Hu K, Rao L, Wu SM, Xiao HB, Gao E: Detection of survivin-expressing circulating cancer cells (CCCs) in peripheral blood of patients with gastric and colorectal cancer reveals high risks of relapse. Ann Surg Oncol. 2008, 15: 3073-3082. 10.1245/s10434-008-0069-x.CrossRefPubMed
22.
go back to reference Hiraiwa K, Takeuchi H, Hasegawa H, Saikawa Y, Suda K, Ando T, Kumagai K, Irino T, Yoshikawa T, Matsuda S: Clinical significance of circulating tumor cells in blood from patients with gastrointestinal cancers. Ann Surg Oncol. 2008, 15: 3092-3100. 10.1245/s10434-008-0122-9.CrossRefPubMed Hiraiwa K, Takeuchi H, Hasegawa H, Saikawa Y, Suda K, Ando T, Kumagai K, Irino T, Yoshikawa T, Matsuda S: Clinical significance of circulating tumor cells in blood from patients with gastrointestinal cancers. Ann Surg Oncol. 2008, 15: 3092-3100. 10.1245/s10434-008-0122-9.CrossRefPubMed
23.
go back to reference Illert B, Fein M, Otto C, Cording F, Stehle D, Thiede A, Timmermann W: Disseminated tumor cells in the blood of patients with gastric cancer are an independent predictive marker of poor prognosis. Scand J Gastroenterol. 2005, 40: 843-849. 10.1080/00365520510015557.CrossRefPubMed Illert B, Fein M, Otto C, Cording F, Stehle D, Thiede A, Timmermann W: Disseminated tumor cells in the blood of patients with gastric cancer are an independent predictive marker of poor prognosis. Scand J Gastroenterol. 2005, 40: 843-849. 10.1080/00365520510015557.CrossRefPubMed
24.
go back to reference Yeh KH, Chen YC, Yeh SH, Chen CP, Lin JT, Cheng AL: Detection of circulating cancer cells by nested reverse transcription-polymerase chain reaction of cytokeratin-19 (K19)--possible clinical significance in advanced gastric cancer. Anticancer Res. 1998, 18: 1283-1286.PubMed Yeh KH, Chen YC, Yeh SH, Chen CP, Lin JT, Cheng AL: Detection of circulating cancer cells by nested reverse transcription-polymerase chain reaction of cytokeratin-19 (K19)--possible clinical significance in advanced gastric cancer. Anticancer Res. 1998, 18: 1283-1286.PubMed
25.
go back to reference Seo JH, Choi CW, Kim BS, Shin SW, Kim YH, Kim JS, Lee SW, Choi JH, Park YT, Mok YJ, Kim CS: Follow-up study of peripheral blood carcinoembryonic antigen mRNA using reverse transcription-polymerase chain reaction as an early marker of clinical recurrence in patients with curatively resected gastric cancer. Am J Clin Oncol. 2005, 28: 24-29. 10.1097/01.coc.0000139018.47930.a5.CrossRefPubMed Seo JH, Choi CW, Kim BS, Shin SW, Kim YH, Kim JS, Lee SW, Choi JH, Park YT, Mok YJ, Kim CS: Follow-up study of peripheral blood carcinoembryonic antigen mRNA using reverse transcription-polymerase chain reaction as an early marker of clinical recurrence in patients with curatively resected gastric cancer. Am J Clin Oncol. 2005, 28: 24-29. 10.1097/01.coc.0000139018.47930.a5.CrossRefPubMed
26.
go back to reference Wu CH, Lin SR, Hsieh JS, Chen FM, Lu CY, Yu FJ, Cheng TL, Huang TJ, Huang SY, Wang JY: Molecular detection of disseminated tumor cells in the peripheral blood of patients with gastric cancer: evaluation of their prognostic significance. Dis Markers. 2006, 22: 103-109.PubMedCentralCrossRefPubMed Wu CH, Lin SR, Hsieh JS, Chen FM, Lu CY, Yu FJ, Cheng TL, Huang TJ, Huang SY, Wang JY: Molecular detection of disseminated tumor cells in the peripheral blood of patients with gastric cancer: evaluation of their prognostic significance. Dis Markers. 2006, 22: 103-109.PubMedCentralCrossRefPubMed
27.
go back to reference Uen YH, Lin SR, Wu CH, Hsieh JS, Lu CY, Yu FJ, Huang TJ, Wang JY: Clinical significance of MUC1 and c-Met RT-PCR detection of circulating tumor cells in patients with gastric carcinoma. Clin Chim Acta. 2006, 367: 55-61. 10.1016/j.cca.2005.11.013.CrossRefPubMed Uen YH, Lin SR, Wu CH, Hsieh JS, Lu CY, Yu FJ, Huang TJ, Wang JY: Clinical significance of MUC1 and c-Met RT-PCR detection of circulating tumor cells in patients with gastric carcinoma. Clin Chim Acta. 2006, 367: 55-61. 10.1016/j.cca.2005.11.013.CrossRefPubMed
28.
go back to reference Mimori K, Fukagawa T, Kosaka Y, Ishikawa K, Iwatsuki M, Yokobori T, Hirasaki S, Takatsuno Y, Sakashita H, Ishii H: A large-scale study of MT1-MMP as a marker for isolated tumor cells in peripheral blood and bone marrow in gastric cancer cases. Ann Surg Oncol. 2008, 15: 2934-2942. 10.1245/s10434-008-9916-z.CrossRefPubMed Mimori K, Fukagawa T, Kosaka Y, Ishikawa K, Iwatsuki M, Yokobori T, Hirasaki S, Takatsuno Y, Sakashita H, Ishii H: A large-scale study of MT1-MMP as a marker for isolated tumor cells in peripheral blood and bone marrow in gastric cancer cases. Ann Surg Oncol. 2008, 15: 2934-2942. 10.1245/s10434-008-9916-z.CrossRefPubMed
29.
go back to reference Pituch-Noworolska A, Kolodziejczyk P, Kulig J, Drabik G, Szczepanik A, Czupryna A, Popiela T, Zembala M: Circulating tumour cells and survival of patients with gastric cancer. Anticancer Res. 2007, 27: 635-640.PubMed Pituch-Noworolska A, Kolodziejczyk P, Kulig J, Drabik G, Szczepanik A, Czupryna A, Popiela T, Zembala M: Circulating tumour cells and survival of patients with gastric cancer. Anticancer Res. 2007, 27: 635-640.PubMed
30.
go back to reference Ambrosini G, Adida C, Altieri DC: A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med. 1997, 3: 917-921. 10.1038/nm0897-917.CrossRefPubMed Ambrosini G, Adida C, Altieri DC: A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med. 1997, 3: 917-921. 10.1038/nm0897-917.CrossRefPubMed
31.
go back to reference Baran J, Pituch-Noworolska A, Krzeszowiak A, Wieckiewicz J, Stachura J, Pryjma J, Popiela T, Szczepanik A, Zembala M: Detection of cancer cells in the blood by FACS sorting of CD45- cells. Int J Mol Med. 1998, 1: 573-578.PubMed Baran J, Pituch-Noworolska A, Krzeszowiak A, Wieckiewicz J, Stachura J, Pryjma J, Popiela T, Szczepanik A, Zembala M: Detection of cancer cells in the blood by FACS sorting of CD45- cells. Int J Mol Med. 1998, 1: 573-578.PubMed
Metadata
Title
Survivin gene levels in the peripheral blood of patients with gastric cancer independently predict survival
Authors
Loris Bertazza
Simone Mocellin
Alberto Marchet
Pierluigi Pilati
Joseph Gabrieli
Romano Scalerta
Donato Nitti
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2009
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-7-111

Other articles of this Issue 1/2009

Journal of Translational Medicine 1/2009 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine