ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy
ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy
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DOI：
10.1200/jco.1998.16.1.309
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发表时间：
1998-01-01
影响因子：
45.3
通讯作者：
Leichman, L
中科院分区：
文献类型：
--
作者：
Metzger, R;Leichman, CG;Leichman, L
目的：我们以前已经表明，在用氟尿嘧啶（5-FU）和顺铂治疗的原发性胃腺癌中，相对胸苷酸合成酶（TS）mRNA水平与反应和生存率呈负相关。这是TS作为5-FU活性靶点的假定功能。我们现在检验切除修复交叉互补（ERCC 1）基因的相对mRNA水平与作为顺铂功效的独立功能的应答和存活负相关的假设。患者有完整的，未经治疗的，原发性胃腺癌，并评估了术前顺铂输注-5-FU方案的合格性。使用来自化疗前原发性胃肿瘤的cDNA来测定ERCC 1 mRNA水平，表示为ERCC 1基因和β-肌动蛋白基因的聚合酶链反应（PCR）产物的比率。结果：38例原发性胃癌（33例可评估缓解）的ERCC 1 mRNA水平中位数为5.8 × 10 - 3（范围为1.8 × 10 - 3至19.5 × 10 - 3）。在17名应答患者中，13名（76%）小于或等于5.8 x 10（-3），4名大于5.8 x 10（-3）（P = .003）。ERCC 1 mRNA水平小于或等于5.8 x 10（-3）的患者的中位生存期尚未达到，而大于5.8 x 10（-3）的患者的中位生存期为5.4个月（P = 0.034）。中位TS mRNA水平为3.7 × 10 - 3（范围0.9 - 18.9），也区分了反应性肿瘤和耐药性肿瘤（P = 0.024）。ERCC 1和TS mRNA水平均低于中位数，13例患者中有11例（85%）有反应; ERCC 1和TS mRNA水平均高于中位数，10例患者中有2例（20%）有反应（P = .003）。结论：单独考虑，原发性胃腺癌中ERCC 1或TS mRNA水平与反应具有统计学显著相关性。ERCC I mRNA水平与生存率具有统计学显著相关性;在该队列中，TS mRNA水平与生存率没有达到我们先前发表的统计学显著相关性。这些分子参数作为预后的预测因子是否相互独立尚待确定。(C)1998年，美国临床肿瘤学会。
Purpose: We have previously shown that relative thymidylate synthase (TS) mRNA levels in primary gastric adenocarcinomas treated with fluorouracil (5-FU) and cisplatin are inversely associated with response and survival. This is a presumed function of TS as a target for 5-FU activity, We now test the hypotheses that the relative mRNA level of the excision repair crosscomplementing (ERCC1) gene is inversely associated with response and survival as an independent function of cisplatin efficacy.Patients and Methods: Patients had intact, untreated, primary gastric adenocarcinoma cancer and were evaluated for eligibility on a preoperative cisplatin infusion-5-FU protocol. cDNA, derived from primary gastric tumors before chemotherapy, was used to determine ERCC1 mRNA levels, expressed as the ratio of polymerase chain reaction (PCR) product of the ERCC1 gene and the beta-actin gene.Results: The median ERCC1 mRNA level from 38 primary gastric cancers (33 assessable for response) was 5.8 x 10(-3) (range, 1.8 x 10(-3) to 19.5 x 10(-3)). Of 17 responding patients, 13 (76%) were less than or equal to 5.8 x 10(-3) and four were greater than 5.8 x 10(-3) (P = .003). The median survival for patients with ERCC1 mRNA levels less than or equal to 5.8 x 10(-3) has not been reached, whereas for those greater than 5.8 x 10(-3) it was 5.4 months (P = .034). The median TS mRNA level, 3.7 x 10(-3) (range, 0.9 to 18.9) also segregated responsive versus resistant tumors (P = .024). With both ERCC1 and TS mRNA levels below their medians, 11 of 13 patients (85%) responded; with both ERCC1 and TS mRNA levels above their medians, two of 10 patients (20%) responded (P = .003).Conclusion: Considered separately, either ERCC1 or TS mRNA levels in a primary gastric adenocarcinoma has a statistically significant relationship to response. ERCC I mRNA levels have a statistically significant association with survival; in this cohort TS mRNA levels did not reach statistically significant association with survival as in our previous publication. Whether these molecular parameters are independent of each other as predictors of outcome remains to be determined. (C) 1998 by American Society of Clinical Oncology.