title: Expression of activated signal transducer and activator of transcription 3 predicts poor clinical outcome in gastric adenocarcinoma.
abstract: There are no known reliable biomarkers which can predict poor clinical outcome following curative resection of gastric adenocarcinoma. Given the importance of signal transducer and activator of transcription 3 (STAT3) activation in carcinogenesis, we attempted to determine whether STAT3 activation is prognostic of survival in curatively resected gastric cancer patients. We analyzed 311 surgically resected gastric cancer specimens for STAT3 activation and its downstream molecules such as matrix metalloproteinase (MMP)-9, MMP-10, cyclin D1, survivin, vascular endothelial growth factor (VEGF)-C, and VEGFR-3 using immunohistochemical studies and assessed their correlation with clinical outcome. Using immunohistochemistry, 303 specimens were interpretable for pSTAT3tyr705 expression. The pSTAT3 was detected in 79 (26.1%) of 303 gastric cancers. Of the downstream molecules tested, STAT3 activation was significantly associated with MMP-9 and MMP-10 expressions. On univariate analyses, 5-year disease-free survival (DFS) and overall survival (OS) for the tumors with STAT3 activation were considerably poorer than for those without STAT3 activation with statistical significance (5-year DFS 58.2% vs 68.3%; pSTAT3(-) vs pSTAT3(+); p = 0.0223; 5-year OS 59.5% vs 70.5%; pSTAT3(-) vs pSTAT3(+); p = 0.0128). On multivariate analyses, STAT3 activation was independently associated with inferior DFS (p = 0.049, hazard ratio [HR] = 1.445, 95% CI, 1.025, 2.120) along with AJCC stage IIIA or IIIB (p = 0.004, HR = 1.708, 95% CI, 1.178, 2.475). The STAT3 activation was also strongly correlated with inferior OS (p = 0.042, HR = 1.506, 95% CI, 1.025, 2.213). Based on our data, pSTAT3tyr705 may be a novel prognostic marker for poorer clinical outcome following curative resection and adjuvant therapy in gastric cancer. The clinical impact of a STAT3-targeted agent should be investigated in gastric cancer patients.
authors: Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Jeeyun
authors: J
authors: Lee
authors: Won Ki
authors: WK
authors: Kang
authors: Joon Oh
authors: JO
authors: Park
authors: Se Hoon
authors: SH
authors: Park
authors: Young Suk
authors: YS
authors: Park
authors: Ho Yeong
authors: HY
authors: Lim
authors: Junga
authors: J
authors: Kim
authors: Jeehyun
authors: J
authors: Kong
authors: Min Gew
authors: MG
authors: Choi
authors: Tae Sung
authors: TS
authors: Sohn
authors: Jae Hyung
authors: JH
authors: Noh
authors: Jae Moon
authors: JM
authors: Bae
authors: Sung
authors: S
authors: Kim
authors: Do Hoon
authors: DH
authors: Lim
authors: Kyoung-Mee
authors: KM
authors: Kim
authors: Cheol Keun
authors: CK
authors: Park
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality* / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D053506:Matrix Metalloproteinase 10 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D050796:STAT3 Transcription Factor / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000401:mortality* / Q000473:pathology; D000077022:Survivin; D046888:Tissue Array Analysis; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077022:Survivin; D042582:Vascular Endothelial Growth Factor C; D019938:Cyclin D1; D040321:Vascular Endothelial Growth Factor Receptor-3; C511770:MMP10 protein, human; D053506:Matrix Metalloproteinase 10; D020780:Matrix Metalloproteinase 9