近日,，美國《國立癌癥研究院院刊》（JNCI）發(fā)表了南京大學醫(yī)學院附屬鼓樓醫(yī)院腫瘤中心魏嘉博士撰寫的胃癌個體化療的最新成果,，并配發(fā)了編者按。該論文的發(fā)表標志著中國胃癌個體化療進入了一個新階段,。
據了解,，該研究是通過對胃癌病人長期治療和隨訪，結合系列性基因標志的篩查,，發(fā)現(xiàn)胃癌腫瘤組織中BRCA1 mRNA表達水平可以預測胃癌患者是否可從含“多西紫杉醇”的化療方案中獲益。BRCA1高表達的患者接受“多西紫杉醇”化療生存時間為24.9月，而BRCA1低表達者僅9.5月,。該發(fā)現(xiàn)首次為個體化療在胃癌的推廣應用提供了科學依據,。
鼓樓醫(yī)院腫瘤中心主任劉寶瑞說：“通過對相關基因的研究，讓我們可以鎖定一些關鍵指標來指導我們用藥,。比如,，在對一個晚期胃癌患者進行治療前,，我們就可以先通過檢測這個指標來判斷患者是否適合采取某類藥物的治療方案,。如果預測評估的效果不理想,，我們就可以直接采取其他的方法來減輕患者痛苦、延長患者生命,。這在對腫瘤患者的治療中，可以爭取到至關重要的時間,，同時可以減輕患者的痛苦和經濟負擔,。”
南京鼓樓醫(yī)院腫瘤中心自2004年起就在國內率先開展胃癌個體化療的臨床轉化醫(yī)學研究。在博士生導師劉寶瑞和錢曉萍的帶領下，魏嘉等博士先后針對胃癌常用化療藥物紫杉醇,、鉑類療效相關基因進行了全面研究,，在基因多態(tài)性等多層次的科學驗證，闡明了諸多基因分子在胃癌個體化療中的作用,，獲得了一批有價值的結果，有20篇SCI論文發(fā)表,，并多次參加國際會議交流。
在此基礎上,，南京大學醫(yī)學院附屬鼓樓醫(yī)院腫瘤中心開展了“BRCA1 mRNA表達水平指導下進展期胃癌個體化療的隨機對照前瞻性研究”,。該項目針對晚期胃癌患者，在其接受治療前檢測藥物敏感相關基因表達水平，選擇預計有效率高的化療藥物,，設計最佳化療方案,，從而提高腫瘤治療效果,，改善腫瘤患者預后,。（生物谷Bioon.com）
doi:10.1093/jnci/djr326
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mRNA Expression of BRCA1, PIAS1, and PIAS4 and Survival After Second-line Docetaxel in Advanced Gastric Cancer
Jia Wei, Carlota Costa, Yitao Ding, Zhengyun Zou, Lixia Yu, Jose Javier Sanchez, Xiaoping Qian, Hong Chen, Ana Gimenez-Capitan, Fanqing Meng, Teresa Moran, Susana Benlloch, Miquel Taron, Rafael Rosell and Baorui Liu
Breast cancer susceptibility gene 1 (BRCA1) has a central role in chemotherapy-induced DNA damage response. The protein inhibitor of activated STAT (PIAS) family of proteins, PIAS1 and PIAS4, are also necessary for adequate DNA damage repair. To further understand the role of BRCA1 in DNA repair, we examined the mRNA expression of these genes in 133 advanced (stage III–IV) gastric cancer patients using quantitative reverse transcription polymerase chain reaction. All P values were two-sided. The median overall survival was 12.5 months (95% confidence interval [CI] = 9.8 to 13.4 months). Among 59 patients receiving second-line docetaxel, the median overall survival was 25.8 months (95% CI = 9.2 to 42.4 months) for patients with high BRCA1 expression, 19.1 months (95% CI = 3.4 to 34.8 months) for those with intermediate expression, and 9.5 months (95% CI = 8.7 to 10.2 months) for those with low expression (P = .0062). The risk of mortality was higher in patients with low BRCA1 levels compared with high BRCA1 levels (hazard ratio of death = 2.49, 95% CI = 1.03 to 5.97, P = .037). Survival in patients receiving second-line docetaxel-based chemotherapy showed a similar trend with PIAS1 and PIAS4 mRNA expression levels, although the associations for PIAS4 were not statistically significant.
