The objective of the study was to compare the gene mutation status among the primary tumor, matched metastatic lymph node (LN) and peripheral blood in advanced nonsquamous non-small cell lung cancer (NSCLC) using next-generation sequencing (NGS).

Many gene mutations have been detected in lung cancer, which might differ between the primary tumor and the metastases in a same patient. One may cause by the heterogenicity of the tumor, another may cause by the sensitivity of the detection technique. So we determine to use NGS, which is a more sensitive technique, to detect the different gene mutations among the primary tumor, metastatic LN and peripheral blood in advanced nonsquamous NSCLC.

The study was designed as a prospective and single center study. Thirty five patients will be enrolled into the study and the clinical data of the patients, including his smoke history, cancer history, occupation exposure and so on, will be collected and recorded in a case report form. For the patients recruited in the study, the primary tumor and metastatic lymph nodes will be obtained by interventional pulmonology technology. And about 10ml peripheral blood will be collected at the same time. The tissue will be sent to Pathology Department of Shanghai Chest Hospital and will be processed with paraffin-embedded, and for those diagnosed with nonsquamous NSCLC, the rest tissue will be extracted with DNA and performed NGS for the qualified DNA sample using Illumina Nextseq500 sequencer.The matched peripheral blood will also be extract with DNA and performed NGS using Illumina Nextseq500 sequencer.

Inclusion Criteria:

1. Patients who are suspected with nonsquamous non-small cell lung cancer according to the clinical, lab examination and imaging data and had never been diagnosed as primary lung cancer before will be enrolled into the study.
2. The clinical stage of the patients should be in stage IIIA-IV judged by the imaging data and can't receive surgery initially,
3. There exist at least one primary tumor and at least one enlarged LN which can be biopsied by minimally invasive techniques.

Exclusion Criteria:

1. The patient is highly suspected to benign lesion, small cell lung cancer and squamous cell carcinoma according to the clinical data.
2. Surgery was considered to be the primary treatment.
3. Patients who are diagnosed with lung cancer and received treatment with drugs or recurrent with lung cancer will be excluded.