Prognostic significance of promyelocytic leukemia expression in gastrointestinal stromal tumor; integrated proteomic and transcriptomic analysis

作者: Hiroshi Ichikawa , Akihiko Yoshida , Tatsuo Kanda , Shin‐ichi Kosugi , Takashi Ishikawa

DOI: 10.1111/CAS.12565

关键词:

摘要: Prognostic markers are urgently needed to optimize the postoperative treatment strategies for gastrointestinal stromal tumors (GIST). GIST of small intestine (I-GIST) show more aggressive behavior than those stomach (S-GIST), and molecular background malignancy in I-GIST may include potential prognostic biomarkers. We conducted integrated proteomic transcriptomic analysis identify genes showing differential expressions according tumor site. generated protein expression profiles four cases each surgically resected S-GIST using label-free analysis. For proteins expressions, global mRNA was compared between 9 23 S-GIST. Among 2555 analyzed, we found that promyelocytic leukemia (PML), a suppressor gene, significantly downregulated at both levels (P < 0.01; fold difference ≥2.0). Immunohistochemistry 254 additional from multiple clinical facilities showed PML-negative were frequent group (P < 0.001). The 5-year recurrence-free survival rate lower PML-positive (60.1% vs 91.7%; P < 0.001). Multivariate revealed downregulation PML an independent unfavorable factor (hazard ratio = 2.739; P = 0.001). Our study indicated prognostication based on have optimizing strategy patients. Further validation studies application, investigation mechanistic significance clarify backgrounds warranted.

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