ostic marker and its relative place relative to key and currently used variables. CYFRA 211, an extensively described NSCLC marker, was simultaneously evaluated in this study and high pre-treatment CYFRA 211 level was considered an independent prognostic marker. The congruent hazard ratios for high CYFRA 211 level in this work and in the larger population PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19705034 of a study we published previously support the reliability of these survival analyses. In conclusion, a high serum HE4 level at diagnosis is an independent determinant of poor prognosis in NSCLC. ~~ Lung cancer is the leading cause of cancer-related death worldwide. Non-small-cell lung cancer is the most common histologic type of the disease and accounts for approximately 80% of lung cancers. Because more than 70% of patients with lung cancer are diagnosed with advanced-stage disease, systemic treatment plays an important role in clinical management. Chemotherapy has been the cornerstone of treatment for NSCLC for many years. However, epidermal growth factor receptor tyrosine kinase inhibitors, such as erlotinib, gefitinib and icotinib, have been shown to greatly improve clinical outcomes and safety when compared with chemotherapy in some patients with advanced NSCLC. EGFR-TKI sensitivity has been associated with activating mutations in the kinase domain of the EGFR gene, especially an exon 19 deletion and mutations in exon 21 and exon 18 . All EGFR gene TKI-sensitive mutations result in activation of the EGFR tyrosine kinase domain, which is the SNDX-275 site target of EGFR-TKIs. Therefore, patients with these EGFR gene TKI-sensitive mutations have a significantly better PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19705642 response to EGFR-TKIs, whereas those with wild-type EGFR genes exhibit a worse tumor response. Assessment of EGFR gene mutation status is critically important for therapeutic decision-making. National comprehensive cancer network guidelines state that DNA mutational analysis in tumor cells is the preferred method to assess EGFR gene mutation status. However, in some cases, tumor tissue either is inadequate for molecular testing because of its small quantity or very low tumor content or is not readily available. Several groups have detected EGFR gene mutations in DNA isolated from plasma or serum samples, which serve as substitutes for tumor tissue; some groups have demonstrated a correlation between mutation status in the plasma/serum and tumor tissue. Furthermore, EGFR gene mutations detected in plasma or serum may be predictive of the response to EGFR-TKIs. However, the methods used to assess EGFR gene mutation status in plasma or serum samples 
are not approved by the current guidelines. Thus, other sensitive and noninvasive approaches for evaluating EGFR gene mutation status using surrogate tumor tissues to predict EGFR-TKI efficacy are still needed. 2 / 17 Classification of EGFR in NSCLC Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry is a sensitive, rapid, inexpensive, and simple technique for proteomic analysis of complex biological samples, such as tissue, urine and blood. Peaks in the mass spectrum correspond to ions formed from relatively abundant species in the sample, predominantly peptides and proteins. Recently, peptide mass fingerprinting based on MALDI-TOF-MS has been widely used to detect diagnostic, prognostic, and predictive proteomic biomarkers. In recently published studies, peptide mass fingerprinting has been successfully applied to analyze serum from patients and healthy controls