Clinical implication of CXCL12 expression in gastric cancer.
OBJECTIVE
Recent research has revealed that tumor cells expressing chemokine receptors have a crucial impact on patient survival. However, there is no information regarding chemokine expression in gastro-intestinal cancer. This study immunohistochemically investigated CXCL12 expression in gastric cancer and evaluated its association with clinical factors, including patient prognosis.


METHODS
A total of 185 gastric cancer patients receiving curative gastrectomy were assessed. CXCL12 expression was evaluated by immunohistochemical analysis. Tumors with CXCL12-positive cancer cells were regarded as CXCL12 positive, and according to the degree of CXCL12 expression, patients were divided into three groups (weak, 31 cases; moderate, 27 cases; strong, 20 cases). Correlations between CXCL12 expression and clinical factors in gastric cancer were then determined.


RESULTS
CXCL12 was found in the cellular membrane of cancer cells. Seventy-four of 185 patients were classified into the CXCL12-positive group. Patients were divided into three groups according to the positivity of CXCL12 expression. Significant associations between CXCL12 and lymph node metastases (p < 0.05), depth of invasion (p < 0.01), lymphatic invasion (p < 0.01), tumor diameter (p < 0.05), and clinical stage (p < 0.01) were seen. Univariate analysis revealed that the CXCL12-positive group had significantly poorer surgical outcome than the CXCL12-negative group (p < 0.01). Multivariate analysis revealed CXCL12 to be an independent prognostic factor in gastric cancer (p = 0.02).


CONCLUSIONS
Cancerous CXCL12 positivity was determined to be an independent prognostic factor in gastric cancer, with CXCL12-positive gastric cancer showing more-aggressive behavior. Autocrine CXCL12 secretion from tumor cells may activate CXCR-4 on the tumor cells, which may be related to of the viability of distant metastases.
Ishigami
Sumiya
S
Digestive Surgery Surgical Oncology, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan. ishiga@m.kufm.kagoshima-u.ac.jp
Natsugoe
Shoji
S
Okumura
Hiroshi
H
Matsumoto
Masataka
M
Nakajo
Akihiro
A
Uenosono
Yoshikazu
Y
Arigami
Takaaki
T
Uchikado
Yasuto
Y
Setoyama
Tetsuro
T
Arima
Hideo
H
Hokita
Shuichi
S
Aikou
Takashi
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate
D014408:Biomarkers, Tumor; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12