Gene expression profile prospectively predicts peritoneal relapse after curative surgery of gastric cancer.
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 approximately 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.
Takeno
Atsushi
A
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Takemasa
Ichiro
I
Seno
Shigeto
S
Yamasaki
Makoto
M
Motoori
Masaaki
M
Miyata
Hiroshi
H
Nakajima
Kiyokazu
K
Takiguchi
Shuji
S
Fujiwara
Yoshiyuki
Y
Nishida
Toshiro
T
Okayama
Toshitsugu
T
Matsubara
Kenichi
K
Takenaka
Yoichi
Y
Matsuda
Hideo
H
Monden
Morito
M
Mori
Masaki
M
Doki
Yuichiro
Y
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D020411:Oligonucleotide Array Sequence Analysis; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D011446:Prospective Studies; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D015996:Survival Rate; D016896:Treatment Outcome; D054928:Validation Studies as Topic
D014408:Biomarkers, Tumor