Expression of the anaphylatoxin C5a receptor in gastric cancer: implications for vascular invasion and patient outcomes.
The C5a receptor (C5aR) expressed in various types of cancers is involved in C5a-induced cancer cell invasion. However, its role in gastric cancer has not yet been fully elucidated. Therefore, we studied the clinical significance of C5aR expression in gastric cancer. The association of C5aR expression in gastric cancer, determined by immunostaining using the anti-C5aR antibody, with clinicopathological parameters and outcomes was evaluated in 148 patients. Further, the association of C5aR expression in liver metastatic sites with clinicopathological parameters was investigated in a separate cohort of 58 patients who underwent hepatectomy. High tumoral C5aR expression (n = 45, 30.4 %) was significantly related to tumor location, cancer invasion depth, vascular and lymphatic invasion, and tumor stage. The 5-year recurrence-free and overall survival rates of patients with high tumoral C5aR expression were significantly lower than those of patients with low tumoral C5aR expression (50.9 vs. 84.2 %, P = 0.002 and 58.8 vs. 86.1 %, P = 0.007, respectively). The incidence of liver metastasis was significantly higher in patients with high tumoral C5aR expression (13.3 %) than in those with low tumoral C5aR expression (3.9 %; P = 0.04). C5aR expression at liver metastatic sites was associated with the C5aR expression status at the primary site (P = 0.0004), vascular invasion at the primary site (P = 0.04), and tumor size at the metastatic site (P = 0.01). C5aR expression in gastric cancer was associated with cancer progression, liver metastasis, and poor prognosis. Therefore, C5aR may represent a prognostic factor and therapeutic target in gastric cancer.
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
Hidetoshi
H
Nitta
Clinical Research Support Center Kyushu, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan.
Takayuki
T
Shimose
Department of Surgery, Saiseikai Fukuoka General Hospital, 1-3-46. Tenjin, Chuo-ku, Fukuoka, Japan.
Yasunori
Y
Emi
Department of Molecular Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, Japan.
Takahisa
T
Imamura
Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, Japan.
Koji
K
Ohnishi
Department of Gastroenterological Surgery/Clinical Research Institute Cancer Research Division, National Kyushu Medical Center, 1-8-1, Jigyouhama, Chuo-ku, Fukuoka, Japan.
Tetsuya
T
Kusumoto
Department of Gastroenterological Surgery, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka, Japan.
Manabu
M
Yamamoto
Department of Surgery, Oita Red Cross Hospital, 3-2-37, Chiyomachi, Oita-shi, Oita, Japan.
Kengo
K
Fukuzawa
Department of Surgery, Matsuyama Red Cross Hospital, 1, Bunkyomachi, Matsuyama-shi, Ehime, Japan.
Ikuo
I
Takahashi
Department of Surgery, Steel Memorial Yawata Hospital, 1-1-1, Harunomachi, Yahatahigashi-ku, Kitakyushu-shi, Fukuoka, Japan.
Hidefumi
H
Higashi
Department of Medical Oncology, Kobe City Medical Center General Hospital, 2-1-1, Minatojimaminamimachi, Chuo-ku, Kobe-shi, Hyougo, Japan.
Akihito
A
Tsuji
Department of Surgery, Kurume University School of Medicine, 67, Asahimachi, Kurume-shi, Fukuoka, Japan.
Yoshito
Y
Akagi
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan.
Eiji
E
Oki
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan.
Yoshihiko
Y
Maehara
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan. hdobaba@kumamoto-u.ac.jp.
Hideo
http://orcid.org/0000-0003-3963-8653
H
Baba
D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D011379:Prognosis; D044087:Receptor, Anaphylatoxin C5a / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*
D044087:Receptor, Anaphylatoxin C5a
C5a; C5a receptor; Gastric cancer; Invasion; Liver metastasis
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