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Hypoxia Inducible Factor-1alpha (HIF-1A) plays different roles in Gallbladder Cancer and Normal Gallbladder Tissues.

Abstract：

:Purpose: Hypoxia-inducible factor-1alpha (HIF-1A) is a transcription factor that plays an "angiogenic switch" role especially under hypoxia microenvironment in solid tumor. However, the functions and clinical significance of HIF-1A in gallbladder cancer (GBC) are still controversial, and it has not been studied in normal gallbladder tissues. In this study, we sought to clarify the role of sub-cellular localization of HIF-1A expression in GBC and normal gallbladder tissues. Methods: The expressions of HIF-1A and CD34 in 127 GBC and 47 normal gallbladder tissues were evaluated by immunohistochemistry. Cox's proportional hazards model analysis and Kaplan-Meier method analysis were used to assess the correlations between these factors and clinicopathological features and prognosis. Results: HIF-1A was expressed in both cytoplasm and nucleus of GBC and normal control tissues, and was significantly correlated with microvessel density (MVD). GBC tissues with positive nuclear HIF-1A expression had higher MVD compared to that with positive cytoplasmic HIF-1A expression; however, in normal gallbladder tissues, samples with positive cytoplasmic HIF-1A had higher MVD compared to that with positive nuclear HIF-1A expression. Moreover, GBC with nuclear HIF-1A expression tended to be more poorly differentiated and had larger tumor size compared to that with cytoplasm HIF-1A expression. Furthermore, GBC patients with nuclear HIF-1A positive were significantly correlated with worse overall survival (OS) compared with cytoplasmic HIF-1A positive. Multivariate Cox regression analysis identified lymph node metastasis and nuclear HIF-1A expression to be independent prognostic parameter in GBC. Conclusions: Our findings provide evidence for the first time that HIF-1A is expressed in normal gallbladder tissues. Nuclear HIF-1A and cytoplasm HIF-1A plays different roles in GBC and normal gallbladder tissues.

journal_name

J Cancer

journal_title

Journal of Cancer

authors

Wu Y,Meng D,You Y,Sun R,Fu M,Yan Q,Zhang S,Fang Z,Bao J,Li Y

doi

10.7150/jca.46749

subject

Has Abstract

pub_date

2021-01-01 00:00:00

pages

827-839

issue

issn

1837-9664

pii

jcav12p0827

journal_volume

pub_type

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Hypoxia Inducible Factor-1alpha (HIF-1A) plays different roles in Gallbladder Cancer and Normal Gallbladder Tissues.