Annexin II overexpression predicts rapid recurrence after surgery in pancreatic cancer patients undergoing gemcitabine-adjuvant chemotherapy.
BACKGROUND
Gemcitabine has been shown to exhibit significant clinical activity against pancreatic cancer and has become a first-line chemotherapeutic for this disease in recent years. However, there are still many patients who do not respond to this treatment and it is expected to improve the clinical outcome if we can develop a method to predict the efficacy of gemcitabine before treatment. The purpose of this study was to determine novel factors that make pancreatic cancer resistant to gemcitabine.


METHODS
Using the high-resolution proteomic approach, agarose two-dimensional gel electrophoresis, we compared protein profiling of a gemcitabine-resistant pancreatic cancer cell line with its wild-type.


RESULTS
We identified Annexin II as an up-regulated protein in the gemcitabine-resistant pancreatic cancer cell line. Immunohistochemistry demonstrated that Annexin II was mainly expressed at the cell surface of pancreatic cancer cells. Interestingly, Annexin II overexpression in cancer cells was significantly associated with rapid recurrence after gemcitabine adjuvant chemotherapy in postoperative patients (P = .0078), and its staining was also an independent prognostic indicator of recurrence in pancreatic cancer patients who underwent adjuvant gemcitabine treatment after curative surgery on multivariate analysis (P = .0047). In addition, inhibition of Annexin II expression by siRNA in pancreatic cancer cell lines increased the cytotoxic efficacy of gemcitabine. These results indicate that Annexin II overexpression may induce gemcitabine resistance in pancreatic cancer resulting in rapid recurrence.


CONCLUSIONS
Analysis of Annexin II expression in cancer tissues may predict the clinical outcome of gemcitabine treatment, leading to the development of a new method for tailor-made treatment for this disease.
Takano
Shigetsugu
S
The Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Togawa
Akira
A
Yoshitomi
Hideyuki
H
Shida
Takashi
T
Kimura
Fumio
F
Shimizu
Hiroaki
H
Yoshidome
Hiroyuki
H
Ohtsuka
Masayuki
M
Kato
Atsushi
A
Tomonaga
Takeshi
T
Nomura
Fumio
F
Miyazaki
Masaru
M
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D000368:Aged; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism*; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D015153:Blotting, Western; D018196:Carcinoma, Adenosquamous / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D002470:Cell Survival / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000188:drug therapy / Q000601:surgery; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
D017306:Annexin A2; D000964:Antimetabolites, Antineoplastic; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D003841:Deoxycytidine; D000093542:Gemcitabine