Published online Jun 14, 2018. doi: 10.3748/wjg.v24.i22.2381
Peer-review started: February 12, 2018
First decision: February 24, 2018
Revised: March 8, 2018
Accepted: April 16, 2018
Article in press: April 15, 2018
Published online: June 14, 2018
Processing time: 119 Days and 19.4 Hours
The poor prognosis of patients diagnosed with gastric cancer (GC) reflects the limitation of our arsenal of anticancer therapeutic strategies. Hypoxia is a critical factor that shapes the GC microenvironment. However, the involvement of GC cells under such conditions remains poorly explained. Although the core transcription factor of the hypoxia signal pathway hypoxia-inducible factor-1α (HIF-1α) has been studied for decades, its prognostic value in GC is still unclear and controversial.
In a previous report, we demonstrated that prolyl 4-hydroxylase beta (P4HB) is a potential target of HIF-1α, but the exact mechanism was not determined.
The aim of the present study is to evaluate the prognostic value of HIF-1α and P4HB in GC.
This study included 428 patients with confirmed GC who underwent gastrectomy in a single Chinese Cancer Center between 2009 and 2011. Clinicopathologic features as well as immunohistochemical analysis of HIF- 1a and P4HB were determined. Long-term survival of these patients was analyzed using univariate and multivariate analyses.
P4HB was positively correlated with hypoxia-associated genes. HIF-1α and P4HB overexpression were significantly correlation with TNM staging and peritoneum cavity metastasis. In univariate analysis, patients with high HIF-1α expression trend had a shorter disease-free survival and overall survival. P4HB overexpression exhibited similar results. Furthermore, HIF-1α is a clinicopathological predictor of dismal prognosis by multivariate analysis.
The prognostic value of P4HB in GC was first reported. We confirmed that HIF-1α overexpression could be considered a useful independent prognostic biomarker in GC after gastrectomy and is correlated to both poor overall survival and disease-free survival. Taken together with our previous research, we are more determined that P4HB is a hypoxia-associated gene and regulated by HIF-1α.
Our research team will explore the mutual regulatory mechanism of HIF-1 and P4HB in future studies through mass spectrometry analysis and co-immunoprecipitation. In addition, we will explore the relationship between the two biomarkers by establishing animal models.