Xun Yuan, Kongming Wu, Na Han, Qian Chu, Shiying Yu, Yuan Chen

Oncology, Tongji Hospital, Huazhong University of Science and Technology,

Objective:Lung cancer is a heterogeneous group of malignancies with variable prognosis and is divided into two main groups, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), which includes adenocarcinoma (AC), squamous cell carcinoma (SCC) and large cell lung cancer (LCC). Recent advances in diagnosis and targeted therapy have prolonged survival of lung cancer patients. However, further improvement of treatment outcome depends on the novel molecular biomarkers to generate individualized treatment and follow-up schedules. We aimed to discover an easily accessible, highly reproducible, inexpensive biomarker, which might help to identify patients at high risk for disease-progression, recurrence and metastasis. Method: We analyzed gene expression pattern in publicly available cohorts of lung cancer patients and identified a signature of genes which might be involved in lung cancer development and prognosis of patients. To further test the clinical significance of the biomarkers, we examined retrospectively clinical characteristics with serum markers. As both mRNA abundance and serum level of KRT19 were highest expressed in squamous cell carcinoma (SCC), we evaluated the prognostic value of KRT19 by tissue microarray (TMA) in a cohort of SCC. Result: Using microarrays and differential expression analysis, we found that KRT19 and CEACAM5 were upregulated in lung cancer compared with normal tissue. Further analysis suggested that high KRT19 expression was significantly correlated with the presence of SCC, EGFR wtlung cancer, higher stage and shorter survival time of lung cancer patients. We also retrospectively collected clinical data and demonstrated that compared with CEA and NSE, serum KRT19 levels showed the strongest correlation with PFS, OS, RFS and MFS (PFS: HR=1.93; 95%CI, 1.31-2.84, P＜0.001; OS: HR=2.13; 95%CI, 1.05-4.34, P=0.037; RFS: HR=1.43; 95%CI, 0.99-2.06, P=0.059; MFS: HR=1.50; 95%CI, 1.05-2.15, P=0.027), making KRT19 a much better diagnostic and prognostic marker than CEA and NSE for NSCLC. By using tissue microarray (TMA) in a cohort of SCC, protein expression of KRT19 was significantly associated with tumor progression and overall-survival of SCC (HR, 2.206; 95%CI, 1.097-4.437, P=0.027). Conclusion:Our results indicated that high expression of KRT19 indicated tumor progression and predicted a poor prognosis. KRT19 should be considered as a valuable molecular marker in lung cancer, especially in SCC.

Key Words: Non-small cell lung cancer  Molecular marker  KRT19