Abstract
This study aimed to explore the prognostic role of dipeptidyl peptidase 4 (DPP4) expression in hepatocellular carcinoma (HCC). DPP4 expression was measured in formalin-fixed paraffin-embedded specimens that were gathered from 327 HCC patients. Immunohistochemistry analyses were utilized to examine DPP4 expression characteristics and prognostic values (overall survival (OS) and time to recurrence) of DDP4 in HCC tissues. In addition, a patient-derived xenograft (PDX) model was used to assess the correlation between DPP4 expression and tumor growth in vivo. DPP4 was expressed in low levels in HCC tissues in contrast to paired peritumoral tissues (38 cases were down-regulated in a total of 59 cases, 64.4%. P=0.0202). DPP4 expression was significantly correlated with TNM stage (P=0.038), tumor number (P=0.035), and vascular invasion (P=0.024), and significantly reduced in patients who were in TNM stages II and III-V, with multiple tumors, and with microvascular invasion compared to patients with TNM stage I, single tumor, and no microvascular invasion. Notably, HCC tissues with low expression of DPP4 had poor OS (P=0.016) compared with HCC tissues with high expression of DPP4, and results from PDX model showed that tumor growth was significantly faster in HCC patients that lowly expressed DPP4 compared to those with highly expressed DPP4. Our findings suggested that low levels of DPP4 could impact the aggressiveness of HCC and contribute to a poor prognosis.
Highlights
Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed cancers across the globe
Dipeptidyl peptidase-4 (DPP4) protein was decreased in HCC tissues Tissue microarray-based immunohistochemical analysis for detecting DPP4 expression showed that DPP4 was predominantly decreased in HCC tissues (Figure 1A) compared with that of paired peri-tumoral tissues (Figure 1B)
Chi-squared analysis of clinical-pathological variables and DPP4 expression in 327 patients revealed that DPP4 expression was closely correlated with TNM stage (P=0.038), tumor number (P=0.035), and vascular invasion (P=0.024), while DPP4 expression was not correlated with age, sex, HBsAg, serum alpha fetoprotein (AFP), liver cirrhosis, Child-Pugh class, tumor differentiation, or tumor size (Table 1)
Summary
Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed cancers across the globe. It accounts for about 50% of the overall number of cancer cases as well as deaths in China [1,2]. DPP4 is downregulated in tissues of liver cirrhosis [17], endometrial adenocarcinoma tissues [18], and a low serum level of DPP4 was related to a poor prognosis for patients who have esophageal squamous cell carcinoma [19]
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