The predictive role of E2-EPF ubiquitin carrier protein in esophageal squamous cell carcinoma.
The ubiquitin proteasome pathway has been implicated in carcinogenesis. However, the role of E2-EPF ubiquitin carrier protein (UCP) in esophageal cancer remains relatively unstudied. In the study, we examined the mRNA level of circulating tumor cells from 60 esophageal cancer patients by membrane arrays consisting of a panel of potential markers including UCP, compared to 40 normal populations. The predictive capacity of UCP was also assessed by immunohistochemical staining of a retrospective series of 84 biopsied esophageal squamous cell carcinomas in relation to clinical outcome. In addition, we studied in vitro biological changes including tumor growth, metastatic capacity, and the sensitivity to irradiation and cisplatin, after experimental manipulation of UCP expression in esophageal cancer cells. By the data of 25-gene membrane array analysis, UCP was the only factor significantly associated with the extent of tumor burden in esophageal cancer patients. Our immunochemistry findings further indicate that UCP positivity was linked to poor response to neoadjuvant therapy and worse survival. In cell culture, inhibited UCP significantly decrease tumor growth and the capacity for metastasis. The epithelial-mesenchymal transition (EMT) induced by VHL/HIF-1alpha-TGF-beta1 pathway might be the underlying mechanism responsible to the more aggressive tumor growth in UCP-positive esophageal cancer. Our results suggest that UCP was significantly associated with poor prognosis of esophageal cancer and may be a new molecular target for therapeutic intervention for esophageal squamous cell carcinoma.
Chen
Miao-Fen
MF
Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan. miaofen@adm.cgmh.org.tw
Lee
Kuan-Der
KD
Lu
Ming-Shian
MS
Chen
Chih-Cheng
CC
Hsieh
Ming-Ju
MJ
Liu
Yun-Hen
YH
Lin
Paul-Yang
PY
Chen
Wen-Cheng
WC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D004358:Drug Therapy; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D011878:Radiotherapy; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000295:instrumentation / Q000379:methods; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics* / Q000378:metabolism*
D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; C046288:ubiquitin carrier proteins; D044763:Ubiquitin-Conjugating Enzymes