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STAT3 rs4796793 与肺癌风险及铂类化疗的临床结局相关。

STAT3 rs4796793 contributes to lung cancer risk and clinical outcomes of platinum-based chemotherapy.

机构信息

Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Department of Pharmacy, Peking University People's Hospital, 100044, Beijing, China.

出版信息

Int J Clin Oncol. 2019 May;24(5):476-484. doi: 10.1007/s10147-018-01386-7. Epub 2019 Jan 28.

Abstract

BACKGROUND

Signal transducer and activator of transcription (STAT) 3 plays a vital role in carcinogenesis and drug response. Platinum-based chemotherapy is the first-line treatment for lung cancer patients, especially those in advanced stages. In the present study, we investigated the association of STAT3 polymorphism rs4796793 with lung cancer susceptibility, platinum-based chemotherapy response, and toxicity.

METHODS

A total of 498 lung cancer patients and 213 healthy controls were enrolled in the study. 467 of them received at least 2-cycle platinum-based chemotherapy. Unconditional logistical regression analysis was used to assess the associations.

RESULTS

STAT3 rs4769793 G allele carriers had an increased susceptibility of lung cancer [additive model: adjusted OR (95% CI) 1.376 (1.058-1.789), P = 0.017; recessive model: adjusted OR (95% CI) 1.734 (1.007-2.985), P = 0.047]. Rs4769793 was not significantly associated with platinum-based chemotherapy response in lung cancer patients. STAT3 rs4796793 was associated with an increased risk of severe overall toxicity [additive model: adjusted OR (95% CI) 1.410 (1.076-1.850), P = 0.013; dominant model: adjusted OR (95% CI) 1.638 (1.091-2.459), P = 0.017], especially hematological toxicity [additive model: adjusted OR (95% CI) 1.352 (1.001-1.826), P = 0.049].

CONCLUSIONS

STAT3 rs4796793 may be considered as a potential candidate biomarker for the prediction of susceptibility and prognosis in Chinese lung cancer patients. However, well-designed studies with larger sample sizes are required to verify the results.

摘要

背景

信号转导子和转录激活子 3(STAT3)在致癌作用和药物反应中起着至关重要的作用。基于铂的化疗是肺癌患者,特别是晚期患者的一线治疗方法。在本研究中,我们研究了 STAT3 多态性 rs4796793 与肺癌易感性、铂类化疗反应和毒性的关系。

方法

共纳入 498 例肺癌患者和 213 例健康对照者。其中 467 例接受了至少 2 个周期的铂类化疗。采用非条件逻辑回归分析评估相关性。

结果

STAT3 rs4769793 G 等位基因携带者肺癌易感性增加[加性模型:调整后的比值比(95%置信区间)1.376(1.058-1.789),P=0.017;隐性模型:调整后的比值比(95%置信区间)1.734(1.007-2.985),P=0.047]。rs4769793 与肺癌患者铂类化疗反应无显著相关性。STAT3 rs4796793 与严重总毒性风险增加相关[加性模型:调整后的比值比(95%置信区间)1.410(1.076-1.850),P=0.013;显性模型:调整后的比值比(95%置信区间)1.638(1.091-2.459),P=0.017],尤其是血液学毒性[加性模型:调整后的比值比(95%置信区间)1.352(1.001-1.826),P=0.049]。

结论

STAT3 rs4796793 可作为中国肺癌患者易感性和预后预测的潜在候选生物标志物。然而,需要更大样本量的设计良好的研究来验证结果。

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