4)新しい細胞情報解析システムの開発 : 治療成績の向上を目指して(シンポジウム2「子宮体癌治療戦略の新展開」,第63回日本産科婦人科学会・学術講演会)
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Background Endometrial cancers (ECs) classified as low and intermediate-risk based on clinical and pathological features (CPF) are associated with 5% and 15% risk of recurrence. We examined whether a gene expression profile can be used to more accurately predict the prognosis of ECs, excluding the high-risk group of CPF. Methods Selection of candidate gene to predict the prognosis: Sixty ECs in which 22 cases had recurred were included in the screening study. Laser capture microdissection was performed to separate cancer and stromal cells, and microarray analysis of the RNA from the cells was performed. Genes to predict the recurrence were selected based on array analyses of the cancer and stromal cells using Cox's proportional hazard model, and a gene scoring model (GSM) was established based on the cells using a logistic regression model. Establishment of the model to predict the recurrence: Tumor specimens were obtained from 136 ECs (low/intermediate risk: 67/69): 14 had recurred and 122 had not recurred with a median follow-up of 1,830 days. Gene expression profiles were established using custom arrays based on the candidate genes. GSM was established for 68 test cases, and the recurrent score (RS) was calculated based on the GSM in the other 68 cases. Results One hundred forty-three and 79 genes were selected from array analysis of cancer and stromal cells, respectively. The AUCs of (ROC) curves used to predict the recurrence based on the GSM of cancer and stromal cells were 0.8. A custom array of 105 genes was made from candidate genes. The AUCs of ROC curves used to predict the recurrence based on the GSM was 0.9 in 68 test cases. The sensitivity and specificity of CPF was 86% and 48%, respectively. GSM achieved sensitivity of 86% and specificity of 67% based on RS=0.062. Progression-free survival (PFS) was significantly longer in patients with RS≤0.062 than in patients with RS>0.062 (p<0.01); however, CPF was not related with PFS. Conclusions Prognosis of ECs, excluding high-risk group of CPF, can be more accurately predicted based on GSM than on CPF.
- 2011-12-01
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