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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 4/2010

01-04-2010 | Gastrointestinal Oncology

Gene Expression Profile Prospectively Predicts Peritoneal Relapse After Curative Surgery of Gastric Cancer

Authors: Atsushi Takeno, MD, Ichiro Takemasa, MD, Shigeto Seno, PhD, Makoto Yamasaki, MD, Masaaki Motoori, MD, Hiroshi Miyata, MD, Kiyokazu Nakajima, MD, Shuji Takiguchi, MD, Yoshiyuki Fujiwara, MD, Toshiro Nishida, MD, Toshitsugu Okayama, PhD, Kenichi Matsubara, PhD, Yoichi Takenaka, PhD, Hideo Matsuda, PhD, Morito Monden, MD, Masaki Mori, MD, Yuichiro Doki, MD

Published in: Annals of Surgical Oncology | Issue 4/2010

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Abstract

Background

Peritoneal relapse is the most common pattern of tumor progression in advanced gastric cancer. Clinicopathological findings are sometimes inadequate for predicting peritoneal relapse. The aim of this study was to identify patients at high risk of peritoneal relapse in a prospective study based on molecular prediction.

Methods

RNA samples from 141 primary gastric cancer tissues after curative surgery were profiled using oligonucleotide microarrays covering 30,000 human probes. Firstly, we constructed a molecular prediction system and validated its robustness and prognostic validity by 500 times multiple validation by repeated random sampling in a retrospective set of 56 (38 relapse-free and 18 peritoneal-relapse) patients. Secondly, we applied this prediction to 85 patients of the prospective set to assess predictive accuracy and prognostic validity.

Results

In the retrospective phase, repeated random validation yielded ~68% predictive accuracy and a 22-gene expression profile associated with peritoneal relapse was identified. The prediction system identified patients with poor prognosis. In the prospective phase, the molecular prediction yielded 76.9% overall accuracy. Kaplan–Meier analysis of peritoneal-relapse-free survival showed a significant difference between the “good signature group” and “poor signature group” (log-rank p = 0.0017). Multivariate analysis by Cox regression hazards model identified the molecular prediction as the only independent prognostic factor for peritoneal relapse.

Conclusions

Gene expression profile inherent to primary gastric cancer tissues can be useful in prospective prediction of peritoneal relapse after curative surgery, potentially allowing individualized postoperative management to improve the prognosis of patients with advanced gastric cancer.
Appendix
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Literature
1.
Otsuji E, Yamaguchi T, Sawai K, Hagiwara A, Taniguchi H, Takahashi T. Recent advances in surgical treatment have improved the survival of patients with gastric carcinoma. Cancer. 1998;82:1233–7.CrossRefPubMed
2.
Yoo CH, Noh SH, Shin DW, Choi SH, Min JS. Recurrence following curative resection for gastric carcinoma. Br J Surg. 2000;87:236–42.CrossRefPubMed
3.
Yu W, Whang I, Suh I, Averbach A, Chang D, Sugarbaker PH. Prospective randomized trial of early postoperative intraperitoneal chemotherapy as an adjuvant to resectable gastric cancer. Ann Surg. 1998;228:347–54.CrossRefPubMed
4.
Fujimoto S, Shrestha RD, Kokubun M, et al. Positive results of combined therapy of surgery and intraperitoneal hyperthermic perfusion for far-advanced gastric cancer. Ann Surg. 1990;212:592–6.CrossRefPubMed
5.
Abe S, Yoshimura H, Tabara H, et al. Curative resection of gastric cancer: limitation of peritoneal lavage cytology in predicting the outcome. J Surg Oncol. 1995;59:226–9.CrossRefPubMed
6.
Taniguchi K, Yonemura Y, Nojima N, et al. The relation between the growth patterns of gastric carcinoma and the expression of hepatocyte growth factor receptor (c-met), autocrine motility factor receptor, and urokinase-type plasminogen activator receptor. Cancer. 1998;82:2112–22.CrossRefPubMed
7.
Ishii Y, Ochiai A, Yamada T, et al. Integrin alpha6beta4 as a suppressor and a predictive marker for peritoneal dissemination in human gastric cancer. Gastroenterology. 2000;118:497–506.CrossRefPubMed
8.
van de Vijver MJ, He YD, van’t Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347:1999–2009.CrossRefPubMed
9.
van ‘t Veer LJ, Dai H, van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415:530–6.CrossRef
10.
Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.CrossRefPubMed
11.
Golub TR, Slonim DK, Tamayo P, et al. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science. 1999;286:531–7.CrossRefPubMed
12.
Yoshioka S, Takemasa I, Nagano H, et al. Molecular prediction of early recurrence after resection of hepatocellular carcinoma. Eur J Cancer. 2009;45:881–9.CrossRefPubMed
13.
Ramaswamy S, Ross KN, Lander ES, Golub TR. A molecular signature of metastasis in primary solid tumors. Nat Genet. 2003;33:49–54.CrossRefPubMed
14.
Sparano JA, Paik S. Development of the 21-gene assay and its application in clinical practice and clinical trials. J Clin Oncol. 2008;26:721–8.CrossRefPubMed
15.
Cardoso F, Van’t Veer L, Rutgers E, Loi S, Mook S, Piccart-Gebhart MJ. Clinical application of the 70-gene profile: the MINDACT trial. J Clin Oncol. 2008;26:729–35.CrossRefPubMed
16.
Teramoto K, Tada M, Tamoto E, et al. Prediction of lymphatic invasion/lymph node metastasis, recurrence, and survival in patients with gastric cancer by cDNA array-based expression profiling. J Surg Res. 2005;124:225–36.CrossRefPubMed
17.
Chen CN, Lin JJ, Chen JJ, et al. Gene expression profile predicts patient survival of gastric cancer after surgical resection. J Clin Oncol. 2005;23:7286–95.CrossRefPubMed
18.
Motoori M, Takemasa I, Doki Y, et al. Prediction of peritoneal metastasis in advanced gastric cancer by gene expression profiling of the primary site. Eur J Cancer. 2006;42:1897–903.CrossRefPubMed
19.
Motoori M, Takemasa I, Yano M, et al. Prediction of recurrence in advanced gastric cancer patients after curative resection by gene expression profiling. Int J Cancer. 2005;114:963–8.CrossRefPubMed
20.
Dupuy A, Simon RM. Critical review of published microarray studies for cancer outcome and guidelines on statistical analysis and reporting. J Natl Cancer Inst. 2007;99:147–57.CrossRefPubMed
21.
Michiels S, Koscielny S, Hill C. Prediction of cancer outcome with microarrays: a multiple random validation strategy. Lancet. 2005;365:488–92.CrossRefPubMed
22.
Kurokawa Y, Matoba R, Nagano H, et al. Molecular prediction of response to 5-fluorouracil and interferon-alpha combination chemotherapy in advanced hepatocellular carcinoma. Clin Cancer Res. 2004;10:6029–38.CrossRefPubMed
23.
Wang Y, Barbacioru CC, Shiffman D, et al. Gene expression signature in peripheral blood detects thoracic aortic aneurysm. PLoS One 2007;2:e1050.CrossRef
24.
Heyer LJ, Kruglyak S, Yooseph S. Exploring expression data: identification and analysis of coexpressed genes. Genome Res. 1999;9:1106–15.CrossRefPubMed
25.
Kodera Y, Nakanishi H, Ito S, et al. Quantitative detection of disseminated free cancer cells in peritoneal washes with real-time reverse transcriptase-polymerase chain reaction: a sensitive predictor of outcome for patients with gastric carcinoma. Ann Surg. 2002;235:499–506.CrossRefPubMed
26.
Mori K, Aoyagi K, Ueda T, et al. Highly specific marker genes for detecting minimal gastric cancer cells in cytology negative peritoneal washings. Biochem Biophys Res Commun. 2004;313:931–7.CrossRefPubMed
27.
Sakakura C, Hagiwara A, Nakanishi M, et al. Differential gene expression profiles of gastric cancer cells established from primary tumour and malignant ascites. Br J Cancer. 2002;87:1153–61.CrossRefPubMed
28.
Barrier A, Boelle PY, Roser F, et al. Stage II colon cancer prognosis prediction by tumor gene expression profiling. J Clin Oncol. 2006;24:4685–91.CrossRefPubMed
29.
Dettling M. BagBoosting for tumor classification with gene expression data. Bioinformatics. 2004;20:3583–93.CrossRefPubMed
30.
Dudoit S, Fridlyand J., Speed TP. Comparison of discrimination methods for classification of tumors using gene expression data. J Am Stat Assoc. 2002;97:77–87.CrossRef
31.
Bild AH, Yao G, Chang JT, et al. Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Nature. 2006;439:353–7.CrossRefPubMed
32.
Takeno A, Takemasa I, Doki Y, et al. Integrative approach for differentially overexpressed genes in gastric cancer by combining large-scale gene expression profiling and network analysis. Br J Cancer. 2008;99:1307–15.CrossRefPubMed
33.
Jing S, Wen D, Yu Y, et al. GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF. Cell. 1996;85:1113–24.CrossRefPubMed
34.
Treanor JJ, Goodman L, de Sauvage F, et al. Characterization of a multicomponent receptor for GDNF. Nature. 1996;382:80–3.CrossRefPubMed
35.
Funahashi H, Okada Y, Sawai H, et al. The role of glial cell line-derived neurotrophic factor (GDNF) and integrins for invasion and metastasis in human pancreatic cancer cells. J Surg Oncol. 2005;91:77–83.CrossRefPubMed
36.
Spyrou G, Enmark E, Miranda-Vizuete A, Gustafsson J. Cloning and expression of a novel mammalian thioredoxin. J Biol Chem. 1997;272:2936–41.CrossRefPubMed
37.
Raffel J, Bhattacharyya AK, Gallegos A, et al. Increased expression of thioredoxin-1 in human colorectal cancer is associated with decreased patient survival. J Lab Clin Med. 2003;142:46–51.CrossRefPubMed
38.
Grogan TM, Fenoglio-Prieser C, Zeheb R, et al. Thioredoxin, a putative oncogene product, is overexpressed in gastric carcinoma and associated with increased proliferation and increased cell survival. Hum Pathol. 2000;31:475–81.CrossRefPubMed
39.
Rubartelli A, Bonifaci N, Sitia R. High rates of thioredoxin secretion correlate with growth arrest in hepatoma cells. Cancer Res. 1995;55:675–80.PubMed
40.
Toyokuni S, Okamoto K, Yodoi J, Hiai H. Persistent oxidative stress in cancer. FEBS Lett. 1995;358:1–3.CrossRefPubMed
41.
Noike T, Miwa S, Soeda J, Kobayashi A, Miyagawa S. Increased expression of thioredoxin-1, vascular endothelial growth factor, and redox factor-1 is associated with poor prognosis in patients with liver metastasis from colorectal cancer. Hum Pathol. 2008;39:201–8.CrossRefPubMed
42.
Sakuramoto S, Sasako M, Yamaguchi T, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357:1810–20.CrossRefPubMed
Metadata
Title
Gene Expression Profile Prospectively Predicts Peritoneal Relapse After Curative Surgery of Gastric Cancer
Authors
Atsushi Takeno, MD
Ichiro Takemasa, MD
Shigeto Seno, PhD
Makoto Yamasaki, MD
Masaaki Motoori, MD
Hiroshi Miyata, MD
Kiyokazu Nakajima, MD
Shuji Takiguchi, MD
Yoshiyuki Fujiwara, MD
Toshiro Nishida, MD
Toshitsugu Okayama, PhD
Kenichi Matsubara, PhD
Yoichi Takenaka, PhD
Hideo Matsuda, PhD
Morito Monden, MD
Masaki Mori, MD
Yuichiro Doki, MD
Publication date
01-04-2010
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 4/2010
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-009-0854-1

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