Expression of Hepatoma-Derived Growth Factor Is Correlated with Lymph Node Metastasis and Prognosis of Gastric Carcinoma

Abstract

Purpose: Hepatoma-derived growth factor (HDGF) is a unique nuclear/growth factor and might play an important role in the development and progression of carcinomas. In the present study, association of HDGF expression with recurrence and prognosis of gastric carcinoma was examined. Patients and Methods: HDGF expression in 317 patients with gastric carcinoma (233 males and 84 females) with ages ranging from 26 to 81years (median, 60 years) was analyzed by immunohistochemistry. Samples with >90% of tumor cells to express positive immunoreactivity similar to or stronger than that in endothelial cells both for nucleus and cytoplasm were regarded as HDGF index level 2, and others as HDGF index level 1. Results: One hundred and eighty-two cases showed level 1 HDGF expression, whereas 135 cases showed level 2 HDGF expression. Patients with level 2 expression showed higher rates of proximal tumor location (P < 0.0001), large tumor size (P < 0.0001), infiltrative tumor growth (P < 0.0001), presence of vascular and lymphatic invasion (P < 0.0001 for both), presence of lymph node metastasis (P < 0.0001), deep tumor invasion (P < 0.0001), and poorer disease-free and overall survival (P < 0.0001for both) compared to those with level 1expression. Multivariate analysis revealed HDGF expression level as an independent prognosticator for disease-free and overall survival. Conclusion: HDGF expression level was shown to be a prognostic factor for gastric carcinoma.

Prognostic Role of Hepatoma-derived Growth Factor in Solid Tumors of Eastern Asia: a Systematic Review and Meta-Analysis

“…The following articles were also excluded: three duplicated publications (Zhou et al, 2007b;Zhou et al, 2010a;Yang et al, 2014); three without data for HR and 95%CI calculations and adequate contact with the investigators could not be established (Natrajan et al, 2006;Mao et al, 2008;Hanada et al, 2013); two with a sample size<50 (Hsu et al, 2012;Tao et al, 2014); two in which HDGF expression was not detected by IHC methods (Savola et al, 2009;Zhang et al, 2010); three uncorrelated. Finally, 26 cohort studies were found eligible for the meta-analysis (Hu et al, 2003;Ren et al, 2004;Iwasaki et al, 2005;Uyama et al, 2006;Yamamoto et al, 2006;Yoshida et al, 2006;Chang et al, 2007;Yamamoto et al, 2007;Zhou et al, 2007a;Hu et al, 2009;Zhou et al, 2010b;Liu et al, 2011;Wang et al, 2011;Zhang et al, 2011;Chen et al, 2012a;Chen et al, 2012b;Lin et al, 2012;Han et al, 2013;Li et al, 2013a;Li et al, 2013b;Li et al, 2013c;Yang et al, 2013;Guo et al, 2014b;Song et al, 2014;Wang et al, 2014;Zhang et al, 2014), containing 32 datasets (29 datasets for OS; 17 datasets for DFS) were qualified to the standard of the meta-analysis. The main characteristics of the selected studies were summari...…”

“…In recent years, elevated levels of hepatoma-derived growth factor (HDGF) have been observed in a variety of malignancies and high levels of HDGF appears to be associated with increased malignancy across cancers, as witnessed by the correlation with adverse characteristics such as poor patient survival (Hu et al, 2003;Ren et al, 2004;Iwasaki et al, 2005;Uyama et al, 2006;Yamamoto et al, 2006;Yoshida et al, 2006;Chang et al, 2007;Yamamoto et al, 2007;Zhou et al, 2007a;Hu et al, 2009;Savola et al, 2009;Zhang et al, 2010;Zhou et al, 2010b;Liu et al, 2011;Wang et al, 2011;Ye et al, 2011;Zhang et al, 2011;Chen et al, 2012a;Chen et al, 2012b;Hsu et al, 2012;Lin et al, 2012;Han et al, 2013;Hanada et al, 2013;Li et al, 2013a;Li et al, 2013b;Li et al, 2013c;Yang et al, 2013;Guo et al, 2014b;Song et al, 2014;Wang et al, 2014;Yang et al, 2014;Zhang et al, 2014). As a multifunctional protein Bao et al, 2014) widely expressed by many types of human cells, HDGF is involved in the regulations of a myriad of cancer cell activities during cancer transformation (Yang et al, 2013), apoptosis , angiogenesis (Ren et al, 2009), and metastasis (Chen et al, 2012a).…”

What drives intense apoptosis resistance and propensity for necrosis in glioblastoma? A role for Bcl2L12 as a multifunctional cell death regulator

“…71 Similarly, HDGF is overexpressed in many different cancers, including gastrointestinal stromal tumors (GISTs), 72 esophageal carcinoma, 73 pancreatic cancer, 74 hepatocellular carcinoma, 75 non-small cell lung cancer, 76 colorectal cancer 77 and melanoma, 78 and has potent angiogenic, 79 invasive 80 and metastatic potential. 73 Contrasting its role under pathophysiological conditions, such as gliomagenesis, necrosis can also be beneficial for an organism as it constitutes a warning system against toxic exposure. Low toxic insults may incite apoptotic cell death, resulting in cellular shrinkage, formation of apoptotic bodies and efficient engulfment of apoptotic remnants by phagocytes.…”

Downregulation of hepatoma-derived growth factor suppresses the malignant phenotype of U87 human glioma cells

“…Some research suggests that HDGF is involved in aggressive tumor behaviors such as progression, angiogenesis, metastasis and recurrence (11,(19)(20)(21). We previously found that HDGF was overexpressed in glioma tissues and that the more advanced the stage, the higher the expression level of HDGF (14).…”

“…Accumulating clinical evidence demonstrates that HDGF expression is correlated with increased malignancy of different types of tumors and that it could be an independent prognostic factor in a variety of human cancers (10)(11)(12)(13). We recently found that HDGF is overexpressed in glioma specimens, and its expression level may correlate with the clinical pathological grade (14).…”