Serum biomarkers analyzed by LC-MS/MS as predictors for short outcome of non-small cell lung cancer patients treated with chemoradiotherapy.
OBJECTIVE
To find potential serum biomakers that can predict clinical outcome upon treatment in non-small cell lung cancer (NSCLC) by analyzing differential proteins in serum with different sensitivity of chemoradiotherapy (CRT).


METHODS
Sera were collected from 37 NSCLC patients before they were treated with concurrent cisplatin-based CRT. According to the outcome of CRT, the patients were divided into sensitive group and resistant one. The proteins in sera were separated by two-dimensional gel electrophoresis after the high abundance proteins were removed from sera. The significantly differentially expressed proteins between two groups were analyzed by liquid chromatography and tendem mass spectrometry (LC-MS/MS). Then, an additional 50 serum samples were used for ELISA analysis to validate the identified proteins that we got in the experiment.


RESULTS
Proteins in sera of each group were successfully separated on 2D gels. There were significant discrepancies in serum protein expression between NSCLC patients with different CRT sensitivity. Among eight differently expressed proteins, six proteins were successfully identified with five of which higher expressed and one lower expressed in resistant group. The increased Alpha-1-antitrypsin (α1-AT) level in resistant group comparing to sensitive one were validated by ELISA analysis (p<0.05).


CONCLUSIONS
Proteomic approach may serve as a useful method in detecting the potential biomarkers for predicting the outcome of treatment in NSCLC patients. NSCLC patients with high α1-AT level in serum before CRT may have a worse treatment outcome.
Department of Radiation Oncology, Shandong Academy of Medical Sciences, Jinan, People' Republic of China.
W
W
Huang
X
X
Ding
B
B
Li
M
M
Fan
T
T
Zhou
H
H
Sun
Y
Y
Yi
J
J
Zhang
D000230:Adenocarcinoma / Q000097:blood* / Q000473:pathology / Q000628:therapy; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D001798:Blood Proteins / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000473:pathology / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000473:pathology / Q000628:therapy; D059248:Chemoradiotherapy; D002853:Chromatography, Liquid; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed; D011379:Prognosis; D040901:Proteomics; D050397:Radiotherapy, Intensity-Modulated; D053719:Tandem Mass Spectrometry; D043823:Taxoids / Q000008:administration & dosage; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
D014408:Biomarkers, Tumor; D001798:Blood Proteins; D005971:Glutamates; D043823:Taxoids; D000068437:Pemetrexed; D003841:Deoxycytidine; D000077143:Docetaxel; D014747:Vinblastine; D006147:Guanine; D002945:Cisplatin; D000077235:Vinorelbine; D000093542:Gemcitabine