摘要标题：EGFR和ERBB2可以预测携带EGFR敏感突变肺腺癌患者的纵隔淋巴结转移状态

Background: Primary bronchogenic carcinomais the leading cause of cancer-related deaths worldwide and a serious threat to human health[1].Radiotherapy is one of the fundamental treatments for lung cancer; however, thoracic tumour radiotherapy leads to radiation-induced lung injury (RILI) with a 5% to 15% incidence rate. The identification of predictive biomarkers of mediastinal lymph node metastases in lung cancer patients would be an important advancement in personalized cancer therapy. While mediastinal lymph node metastases is a major factor associated with poor prognosis in cancer, little is known of its molecular mechanisms.

研究背景：原发性支气管肺癌是全球癌症相关死亡的主要原因，并且严重威胁人类的健康。放射治疗是肺癌的基本治疗手段之一，然而，胸部肿瘤放疗导致放射性肺损伤(RILI)发生率为5% - 15%。肺癌患者纵隔淋巴结转移的预测生物标志物的识别将是个性化癌症治疗的重要进展。纵隔淋巴结转移是癌症预后不良的主要因素，但其分子机制却鲜为人知。

Methods: Ten patients with lung adenocarcinoma who underwent resection of the primary lesion and lymphadenectomy of mediastinal lymph nodes were included in this study. These 10 samples were divided into two groups: 5 patients for whom mediastinal lymph node metastases occurred within two years were grouped into the trans group, and the other 5 patients for whom mediastinal lymph node metastases did not occur within two years were grouped into the no-trans group. Both tumor RNA and tumor DNA were isolated from pre-treatment paraffin-embedded tumor tissue. Gene expression profiles were obtained using RNA-seq, and gene mutation profiles were obtained using NGS. Gene predictor sets were constructed by evaluating the statistical significance of the expression levels and the mutation frequency of selected genes.

研究方法：本研究纳入了10例接受了原发灶切除和纵隔淋巴结淋巴结切除的肺腺癌患者。这10个样本分为两组：一组是转移组，包括5例在两年内发生纵隔淋巴结转移的患者，另外一组是未转移组，包括5例在两年内未发生纵隔淋巴结转移的患者。从预处理的石蜡包埋肿瘤组织中提取肿瘤RNA和肿瘤DNA。利用RNA-seq测序获得基因表达谱，利用NGS测序获得基因突变谱。通过统计分析相关基因的基因表达水平和基因突变情况来探寻预测基因标志物。

Results: Among the 10 samples，Half of the patients had mediastinal lymph node metastases were found to have high degree of EGFR mutations and ERBB2 expression, and the other half of patients did not had mediastinal lymph node metastases were found to have low degree of EGFR mutations and ERBB2 expression.

研究结果：在10例患者中,5例发生纵隔淋巴结转移的患者,具有较高频率的EGFR突变和较高水平的ERBB2表达;其余5例未发生纵隔淋巴结转移的患者,具有较低频率的EGFR突变和较低水平的ERBB2表达。

Conclusions: The findings of this study showed that high mutation frequencies of EGFR and ERBB2 gene amplification may be predictors for mediastinal lymph node metastases of lung adenocarcinoma, which can confirm the lymph-node field radiotherapy and improve the efficacy of radiotherapy.

研究结论：本研究结果显示，EGFR的高频率突变和ERBB2的高水平表达可能成为肺腺癌纵隔淋巴结转移的生物预测指标，为精确勾画肺腺癌患者的纵隔淋巴结照射野从而改善放射治疗疗效提供依据。