Clinical significance of IGF1R gene expression in patients with Stage II/III gastric cancer who receive curative surgery and adjuvant chemotherapy with S-1.
OBJECTIVE
Curative resection and adjuvant chemotherapy is the standard treatment for Stage II/III gastric cancer, and S-1 is widely used for adjuvant chemotherapy. The type 1 insulin-like growth factor receptor (IGF1R) is involved in cell proliferation and prevention of apoptosis in many tumors. We evaluated the relative expression of the IGF1R gene to determine whether such expression correlates with outcomes in patients with Stage II/III gastric cancer.


METHODS
We measured the expression levels of the IGF1R gene in specimens of cancer and adjacent normal mucosa obtained from 134 patients with Stage II/III gastric cancer who received curative resection and adjuvant chemotherapy with S-1. We then evaluated whether the IGF1R gene expression levels correlate with clinicopathological characteristics and outcomes.


RESULTS
IGF1R mRNA expression levels tended to be higher in cancer tissue than in the normal adjacent mucosa (P = 0.078). Multivariate analysis showed that high IGF1R gene expression was a significant independent predictor of poor survival in Stage II/III gastric cancer after curative resection and adjuvant chemotherapy with S-1 (HR 3.681, P = 0.007). The overall survival rate was significantly lower in patients with high IGF1R gene expression than in those with low expression (P = 0.012).


CONCLUSIONS
IGF1R overexpression is considered a useful independent predictor of outcomes in Stage II/III gastric cancer after curative resection and adjuvant chemotherapy with S-1.
Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Koji
K
Numata
Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. ohshimatakashi@yahoo.co.jp.
Takashi
T
Oshima
Department of Biostatistics, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Kentaro
K
Sakamaki
Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Kazue
K
Yoshihara
Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan.
Toru
T
Aoyama
Department of Gastroenterological Surgery, Yokohama City University Medical Center, 4-57 Urafune, Minami-ku, Yokohama, 232-0024, Japan.
Tsutomu
T
Hayashi
Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Takanobu
T
Yamada
Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan.
Tsutomu
T
Sato
Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan.
Haruhiko
H
Cho
Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan.
Manabu
M
Shiozawa
Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan.
Takaki
T
Yoshikawa
Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Yasushi
Y
Rino
Department of Gastroenterological Surgery, Yokohama City University Medical Center, 4-57 Urafune, Minami-ku, Yokohama, 232-0024, Japan.
Chikara
C
Kunisaki
Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan.
Makoto
M
Akaike
Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Toshio
T
Imada
Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Munetaka
M
Masuda
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D004338:Drug Combinations; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000627:therapeutic use; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000096:biosynthesis / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015996:Survival Rate; D005641:Tegafur / Q000627:therapeutic use
D004338:Drug Combinations; C000597236:IGF1R protein, human; D012333:RNA, Messenger; D017451:Receptors, Somatomedin; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D017526:Receptor, IGF Type 1
Gastric cancer; IGF1R; Prognosis; S-1