title: Increased HIF-1alpha expression in tumor cells and lymphocytes of tumor microenvironments predicts unfavorable survival in esophageal squamous cell carcinoma patients.
abstract: The expression of hypoxia-induced factor (HIF)-1α is up-regulated in tumor microenvironments under hypoxia condition. However, the prognostic significance of HIF-1α in esophageal squamous cell carcinoma (ESCC) is still elusive. We measured the HIF-1α expression by immunochemistry in tumor specimens from 136 resected ESCC; in the current study, the HIF-1α expression in tumor cells was significantly associated with tumor stage (P = 0.003) and lymph node metastasis (P = 0.006); whereas the HIF-1α expression in tumor-infiltrating lymphocytes (TILs) had no relationship with patients' clinicopathological parameters. Patients with high HIF-1α expression in tumor cells or in TILs showed worse survival related to those with low HIF-1α expression. Multivariate analysis demonstrated that expression of HIF-1α in TILs was an independent factor for DFS (P = 0.007) and OS (P = 0.013). Additionally, the expression of HIF-1α in tumor cells was an independent factor for DFS (P = 0.037) and OS (P = 0.033) in locoregional ESCC patients, whereas the expression of HIF-1α in TILs was an independent factor for DFS (P = 0.048) and OS (P = 0.039) in metastatic ESCC patients. Correlation analysis revealed that expressions of HIF-1α in tumor cells and in TILs were positively correlated, and patients with combined high HIF-1α in both tumor cells and TILs had the worst survivals (P < 0.05). These findings suggest that the HIF-1α expressions in different cell populations of ESCC microenvironments have different clinical relevance and prognostic impact on patients.
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center Guangzhou, China ; Department of Clinical Laboratory, Sun Yat-Sen University Cancer Center Guangzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center Guangzhou, China ; Department of Biotherapy, Sun Yat-Sen University Cancer Center Guangzhou, China.
authors.forename: Shu-Biao
authors.initials: SB
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center Guangzhou, China ; Department of Biotherapy, Sun Yat-Sen University Cancer Center Guangzhou, China.
authors.forename: Ze-Lei
authors.initials: ZL
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center Guangzhou, China ; Department of Intensive Care Unite, Sun Yat-Sen University Cancer Center Guangzhou, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Ma
authors.affiliation: Department of Biotherapy, Sun Yat-Sen University Cancer Center Guangzhou, China.
authors.forename: Shi-Ping
authors.initials: SP
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center Guangzhou, China ; Department of Biotherapy, Sun Yat-Sen University Cancer Center Guangzhou, China.
authors.forename: Jia
authors.initials: J
authors.lastname: He
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center Guangzhou, China ; Department of Clinical Laboratory, Sun Yat-Sen University Cancer Center Guangzhou, China.
authors.forename: Wan-Li
authors.initials: WL
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center Guangzhou, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center Guangzhou, China.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center Guangzhou, China ; Department of Biotherapy, Sun Yat-Sen University Cancer Center Guangzhou, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000096:biosynthesis*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit
keywords: Esophageal squamous cell carcinoma; HIF-1α; clinical prognosis; tumor microenvironments; tumor-infiltrating lymphocytes