Comparative proteomic profiling identified sorcin being associated with gemcitabine resistance in non-small cell lung cancer

Although gemcitabine-based chemotherapy is one of the more effective chemotherapy regimens against NSCLC, there are still many patients who do not benefit from this therapy. The mechanism of initial or acquired resistance to gemcitabine chemotherapy remains unknown. In this study, we investigated the protein profiling in gemcitabine-resistant and gemcitabine-sensitive NSCLC cell lines by a proteomic technology in order to identify novel gemcitabine resistance associated biomarkers for NSCLC patients. The proteomic profiling of NSCLC cell line H460 and its gemcitabine-resistant subline H460/GEM were compared by an isotope-coded affinity tag technology and tandem mass spectrometry. We further validated the expression of sorcin, a gemcitabine-resistance-related protein identified by proteomics, in 62 NSCLC specimens by immunohistochemistry. Fourteen gemcitabine resistance-related proteins were identified including nine up-regulated proteins and five down-regulated proteins. Immunohistochemical results demonstrated that sorcin staining was seen in 66.1% of NSCLC tumors, and sorcin overexpression was associated with gemcitabine resistance and a poor prognosis in NSCLC patients. In conclusion, sorcin might play an important role in the resistibility to gemcitabine, and it could also be a novel candidate biomarker for predicting the response of NSCLC patients to gemcitabine treatment.