title: Proteomic identification of predictive tissue biomarkers of sensitive to neoadjuvant chemotherapy in squamous cervical cancer.
abstract: OBJECTIVE
  The regimens of neoadjuvant chemotherapy (NAC) in squamous cervical cancer (SCC) frequently use cisplatin combined with paclitaxel. Unfortunately, some cervical cancers show resistance to the principal chemotherapeutic agents in the treatment, decreasing the effectiveness of this therapy. The objective of this study was to search for predictive markers of response to NAC in patients with SCC.
  
  
  METHODS
  Two-dimensional gel electrophoresis (2-DE) accompanied by matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF-MS) was used to analyze and identify differentially expressed proteins in ten cases of advanced cervical cancer patients receiving cisplatin-based NAC. Each of these patients received more than two cycles of NAC. Cell proliferation rate in cisplatin resistant human cervical cancer cell Hela/DDP and its parent cell Hela after treatment with Hsp70 inhibitor and/or cisplatin were tested by MTT assay.
  
  
  RESULTS
  Twelve protein spots changed in abundance, quantitative comparison of spot volumes showed that seven protein spots were up-regulated and five spots were down-regulated in the NAC non-responders compared to the NAC responders. These proteins are involved in various cellular processes essential for cell metabolism, migration and apoptotic signal transduction. The high-fold changes proteins of stathmin1, Hsp70 and pyruvate kinase isoform M2 were validated by Western blot analysis. Over-expression of Hsp70 inhibits the efficacy of cisplatin. Hsp70 inhibitor enhanced the sensitivity to cisplatin in both Hela and Hela/DDP cells.
  
  
  CONCLUSIONS
  The study found many candidate proteins involved in chemotherapy resistance/sensitivity, among them Hsp70 might be potential biomarkers to predict the efficacy of chemotherapy for SCC patients.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou City 730000, Gansu Province, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Guo
authors.affiliation: The First Hospital of Lanzhou University, Lanzhou City 730000, Gansu Province, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Zhang
authors.affiliation: The First Hospital of Lanzhou University, Lanzhou City 730000, Gansu Province, China.
authors.forename: Jinghong
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Gansu Provincial Hospital, Lanzhou City 730000, Gansu Province, China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: First Affiliated Hospital of Xiamen University, Xiamen City 361003, Fujian Province, China.
authors.forename: Jianfa
authors.initials: J
authors.lastname: Lan
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou City 730000, Gansu Province, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Su
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou City 730000, Gansu Province, China. Electronic address: xdxie@lzu.edu.cn.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xie
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000378:metabolism*; D011237:Predictive Value of Tests; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D002945:Cisplatin
keywords: Drug sensitivity; Neoadjuvant chemotherapy; Proteomics; Squamous cervical cancer