title: High level of serum AMBP is associated with poor response to paclitaxel-capecitabine chemotherapy in advanced gastric cancer patients.
abstract: Gastric cancer is one of the most common human cancers and ranks the second in the global cancer-related mortality. The clinical outcome of patients with advanced gastric cancer (AGC) is markedly dependent on their response to the chemotherapy. Paclitaxel plus capecitabine, as a first-line regimen, is widely administrated in AGC patients, but more than a half of the patients have a poor response, possibly due to their resistance to the treatment. Therefore, it is important to identify potential responders to improve the efficacy of the chemotherapy. In the present study, we used an isobaric tag approach for relative and absolute quantification combined with ESI-QUAD-TOF/MS to identify potential predictive biomarkers for the chemotherapy. We found 211 serum proteins, and confirmed 17 candidates that were differentially present in the progression of disease (PD) group and the partial response (PR) group to the treatment of paclitaxel plus capecitabine. In further validation of the 17 candidates in the set of 12 PD and 12 PR AGC patients, we identified a higher level of AMBP (Alpha-1-Microglobulin/Bikunin Precursor) in the sera of PD patients than of the PR patients assayed by ELISA (9.13 ± 0.45 vs. 8.11 ± 0.26 μg/mL, p = 0.06) and by the Western blotting (relative gray value 396.4 ± 39.1 vs. 275.0 ± 34.76, p = 0.03), respectively. The receiver operating characteristics curve showed 75% sensitivity and 75% specificity of AMBP in AGC patients treated with the chemotherapy. Our data indicated that the high level of serum AMBP could predict the poor response of the AGC patients treated with the paclitaxel-capecitabine chemotherapy, which could be used as a potential biomarker to identify patients who would benefit from this chemotherapeutic regimen.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Huang
authors.forename: Yong
authors.initials: Y
authors.lastname: Han
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.forename: Junnan
authors.initials: J
authors.lastname: Feng
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.forename: Like
authors.initials: L
authors.lastname: Qu
authors.forename: Lin
authors.initials: L
authors.lastname: Shen
authors.forename: Chengchao
authors.initials: C
authors.lastname: Shou
mesh_terms: D000328:Adult; D000368:Aged; D000510:Alpha-Globulins / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*
chemical_list: D000510:Alpha-Globulins; D014408:Biomarkers, Tumor; C016001:alpha-1-microglobulin; D003841:Deoxycytidine; D000069287:Capecitabine; D017239:Paclitaxel; D005472:Fluorouracil