Lung cancer is the leading cause of cancer-related death in the world because of its high morbidity and mortality. Approximately 1.2 million people are diagnosed with lung cancer all over the world per year. Despite the great progresses in cancer research over the last decades, lung cancer remains at a very low 5-year survival rate: 16% compared with 89% for breast cancer, 65% for colon cancer, and 100% for prostate cancer (1). Although lung cancer comprises only about 15% of new cancer diagnosis, it causes over 30% of all cancer-related deaths. Lung cancer is divided into two major clinicopathological classes: small cell lung cancer (ϳ15% of all lung cancer) and non-small-cell lung cancer (NSCLC, ϳ85%).1 The latter includes three major histological subtypes: squamous cell carcinoma (SCC, 40% of NSCLC), adenocarcinoma (AD, 40% of NSCLC), and large cell carcinoma (10% of NSCLC) (2). NSCLC is commonly treated with surgery, whereas small cell lung cancer usually responds better to chemotherapy and radiotherapy. For NSCLC, curative surgery is efficacious only in those who are diagnosed sufficiently early in the disease process. Unfortunately, more than 70% of the patients are diagnosed only at an advanced stage nowadays, which results in the loss of opportunity for curative surgical resection and poor prognosis. To improve the survival of patients with lung cancer, identifying reliable biomarkers for early diagnosis and prognosis prediction and monitoring treatment response remain urgently needed. Proteomic analysis, a powerful tool for global evaluation of protein expression, has been widely applied in cancer reFrom the