Tumor PHD2 Expression Is Correlated With Clinical Features and Prognosis of Patients With HCC Receiving Liver Resection

Abstract

The role of prolyl hydroxylase domain protein 2 (PHD2) in carcinogenesis has been studied in a variety of cancer types. However, the association between PHD2 and human hepatocellular carcinoma (HCC) has not been documented.A total of 220 patients with primary HCC who underwent a curative liver resection were enrolled in this study. The tumor samples were obtained during the surgical procedure from each patient for PHD2 immunohistological staining. All the patients were followed up and the disease-free survival (DFS) and overall survival (OS) were evaluated.We found that that high PHD2 expression was significantly associated with higher stage (stages III + IV) (odds ratio [OR] = 5.576, P < 0.001), larger tumor size (>5 cm) (OR = 6.176, P < 0.001), poorer tumor differentiation (OR = 1.424, P = 0.003), and higher serum alpha fetoprotein (AFP) level (OR = 6.861, P < 0.001). Compared to those with high PHD2 expressions, patients with low PHD2 expression had significantly longer DFS and OS periods (both P < 0.001). Cox regression analyses revealed that higher levels of PHD2, tumor size, tumor stage, as well as serum AFP level were predictors for a worse prognosis in patients with HCC.PHD2 expression in the tumors is associated with the clinical features and prognosis of patients with HCC; it may be used as a histological marker for HCC.

RETRACTED ARTICLE: PHD2 acts as an oncogene through activation of Ras/Raf/MEK/ERK and JAK1/STAT3 pathways in human hepatocellular carcinoma cells

“…The significance of PHD2 expression during HCC has been revealed in our previous study, in which high level of PHD2 has been demonstrated to be associated with the clinical features and poor prognosis of patients with HCC [9]. The data in the present work was in line with previous findings.…”

“…Besides, PHD2 was reported to be essential for regulating glioblastoma progression through a HIF-a-dependent way [8]. Our previous study illustrated that PHD2 expression was associated with HCC progression and poor prognosis of patients with this cancer [9]. However, the deep functions of PHD2 in the onset and progression of HCC were not comprehensively analyzed.…”

Hypoxia inducible factor prolyl hydroxylase 2 (PHD2) is a direct regulator of epidermal growth factor receptor (EGFR) signaling in breast cancer

“…By contrast, studies from a spontaneously arising PyMT-oncogene-driven breast cancer model showed that inhibition of PHD2 significantly decreased the number of metastases in the lung, supporting the prooncogenic role of PHD2 in breast cancer [25]. Studies on head and neck squamous cell carcinoma showed that high expression of PHD2 was associated with an aggressive phenotype [37] and high tumor PHD2 levels in hepatocellular carcinoma (HCC) were associated with higher tumor stage, larger tumor size, and worse overall patient survival [38]. Additionally, in non-small cell lung cancer (NSCLC) high levels of PHD2 were assessed as an independent negative prognostic factor for disease specific survival [39].…”

Hypoxia-Inducible Factor Prolyl 4-Hydroxylases and Metabolism

“…Conflicting data with respect to HIF-P4H-2 expression and HCC in human samples were reported. One study associated high HIF-P4H-2 expression with larger and higher stage tumors and poorer prognosis [100], whereas another one reported an association of lower hepatic HIF-P4H-2 levels with cancerous tissue and a longer patient survival upon elevated HIF-P4H-2 levels [101].…”