Author：Wanning Yang, Lei Xia, Zhenzhou Yang, Henghui Zhang

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.

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.

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.

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.