Profiling protein markers associated with the sensitivity to concurrent chemoradiotherapy in human cervical carcinoma.
Concurrent chemoradiotherapy (CCRT) is recently recommended as the primary and standard treatment modality for cervical cancer. The aim of this study is to investigate the protein biomarkers associated with CCRT sensitivity, so as to better understand the mechanisms underlying CCRT resistance. Fresh tumor tissues from five cases for each group of CCRT-highly sensitive (CCRT-HS) and CCRT-lowly sensitive (CCRT-LS) were analyzed by 2-D electrophoresis coupled with MALDI-TOF-MS, followed by Western blot for four candidate proteins including S100A9, galectin-7, nuclear matrix protein-238 (NMP-238), and heat shock protein-70 (HSP-70). In randomly selected CCRT-HS (n = 60) and CCRT-LS (n = 35) cases, these four differentially expressed proteins were detected by tissue microarray with immunohistochemistry staining to explore the association between these interested proteins and CCRT sensitivity. Nineteen proteins differentially expressed more than four times between two groups were identified. An association was revealed between CCRT sensitivity and increased S100A9 and galectin-7, but decreased NMP-238 and HSP-70 expression (p < 0.001, respectively). Although none of these four protein markers could be used as an independent predictive factor, a recurrence prediction model was generated by combining S100A9, galectin-7, NMP-238, and HSP-70 as a full predictive factor. The proteomic analysis combined with tissue microarray provides us a dramatic tool in predicting CCRT response. The increased expression of S100A9 and galectin-7, but decreased expression of NMP-238 and HSP-70, suggests a significantly increased sensitivity to CCRT in cervical cancer.
Zhu
Hong
H
Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Pei
Hai-ping
HP
Zeng
Shan
S
Chen
Jia
J
Shen
Liang-fang
LF
Zhong
Mei-zuo
MZ
Yao
Ruo-jing
RJ
Shen
Hong
H
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy / Q000628:therapy*; D003131:Combined Modality Therapy; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008875:Middle Aged; D010449:Peptide Mapping / Q000379:methods; D011237:Predictive Value of Tests; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D046888:Tissue Array Analysis; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy / Q000628:therapy*
D014408:Biomarkers, Tumor