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Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations
Published on: November 7, 2019
Comparative proteomic profiling identified sorcin being associated with gemcitabine resistance in non-small cell lung
Yiqing Qu1, Yie Yang, Baoyi Liu
1Department of Respiratory Medicine, Qilu Hospital, Shandong University, 250012, Jinan, China. yiqingqu@126.com
Abstract:
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 resistance to gemcitabine, and it could also be a novel candidate biomarker for predicting the response of NSCLC patients to gemcitabine treatment.
Insights
Researchers identified sorcin as a key protein linked to gemcitabine resistance in non-small cell lung cancer (NSCLC). Sorcin overexpression predicts poor response to gemcitabine chemotherapy in NSCLC patients.
Area of Science:
- Proteomics
- Oncology
- Biomarker Discovery
Background:
- Gemcitabine chemotherapy is a standard treatment for non-small cell lung cancer (NSCLC).
- Many NSCLC patients exhibit intrinsic or acquired resistance to gemcitabine, limiting treatment efficacy.
- The molecular mechanisms underlying gemcitabine resistance in NSCLC are not fully understood.
Purpose of the Study:
- To investigate protein expression differences between gemcitabine-sensitive and resistant NSCLC cells.
- To identify novel protein biomarkers associated with gemcitabine resistance in NSCLC.
- To evaluate the clinical significance of identified biomarkers in NSCLC patient samples.
Main Methods:
- Comparative proteomic analysis using isotope-coded affinity tag (ICAT) technology and tandem mass spectrometry.
- Proteomic profiling of the NSCLC cell line H460 and its gemcitabine-resistant counterpart H460/GEM.
- Immunohistochemical validation of sorcin expression in 62 NSCLC tumor specimens.
Main Results:
- Fourteen proteins differentially expressed in gemcitabine-resistant NSCLC cells were identified (9 upregulated, 5 downregulated).
- Sorcin was identified as a significantly upregulated protein associated with gemcitabine resistance.
- Sorcin overexpression was detected in 66.1% of NSCLC tumors and correlated with gemcitabine resistance and poor prognosis.
Conclusions:
- Sorcin plays a significant role in gemcitabine resistance in NSCLC.
- Sorcin is a potential novel biomarker for predicting NSCLC patient response to gemcitabine therapy.
- Further research into sorcin's role may lead to improved therapeutic strategies for NSCLC.
