Objective: To investigate the role of des-gamma-carboxy prothrombin (DCP) in assessment of liver function and prognosis of patients with liver cirrhosis. Methods: From January 2013 to August 2016, a total of 137 patients with liver cirrhosis in Shanghai Changzheng Hospital were enrolled. The serum DCP level was measured, the clinical data was collected and the complication and survival situation was followed up. The 137 patients were divided into DCP negative group (DCP≤40 mAU/mL, 118 cases) and DCP positive group (DCP>40 mAU/mL, 19 cases). Forty-five patients with compensated liver cirrhosis were divided into high-level DCP group (DCP>16.5 mAU/mL, 32 cases) and low-level DCP group (DCP≤16.5 mAU/mL, 13 cases). Chi square test was used to analyze the difference in the positive rate of DCP in patients with different Child-Pugh classification. Spearman correlation test was performed to analyze the correlation between DCP and model for end-stage liver disease (MELD) scores. Kaplan-Meier survival curve was used to analyze the correlation between DCP and liver disease related mortality. Results: Compared to that of DCP negative group, albumin level of patients in DCP positive group decreased (35 g/L, 20 to 57 g/L vs. 29 g/L, 17 to 42 g/L), however, total bilirubin (TBil), prothrombin time (PT), and international normalized ratio all increased (12.9 mg/L, 1.80 to 83.0 mg/L vs.22.2 mg/L, 6.4 to 169.0 mg/L; 15.5 s, 11.7 to 35.7 s vs.17.5 s, 13.9 to 33.4 s; 1.24, 0.96 to 3.72 vs.1.44, 1.09 to 3.22), and the differences were statistically significant (Z=-2.785, -2.891, -2.945 and -2.879, all P<0.01). The DCP positive (DCP>40 mAU/mL) rates of Child-Pugh A, B and C patients were 1.8% (1/55), 21.2% (11/52) and 23.3% (7/30), respectively, and the difference was statistically significant (χ²=11.246, P=0.003). The DCP levels of patients with Child-Pugh class B and C cirrhosis were significantly correlated with MELD scores (r=0.259, P=0.021). There were 16 and three patients with ascites and spontaneous bacterial peritonitis (SBP) of DCP positive group, and the incidence was higher than that of DCP negative group (55.1%, 65/118 and 1.7%, 2/118), and the differences were statistically significant (χ²=5.744 and 97.636, both P<0.05). Patients in high-level DCP group had a higher proportion of clinical decompensation than low-level DCP group (53.1% (17/32) and two cases), the difference was statistically significant (χ²=5.397, P=0.024). The overall survival rate of DCP positive group (nine survival cases) were lower than that of DCP negative group (87.9%, 87/99), and the difference was statistically significant (χ²=5.442, P=0.020). Conclusions Serum DCP level is closely related to liver function, ascites and SBP in patients with liver cirrhosis. Furthermore, it is associated with occurrence of decompensation in compensated patients and liver-related mortality in patients with liver cirrhosis. DCP may be a useful serum marker for evaluation of disease severity and prognosis in patients with liver cirrhosis in clinical practice.

Immunological evasion is one of the defining characteristics of cancers, as the immune modification of an immune checkpoint (IC) confers immune evasion capabilities to tumor cells. Multiple ICs, such as programmed cell death protein-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), can bind to their respective receptors and reduce tumor immunity in a variety of ways, including blocking immune cell activation signals. IC blockade (ICB) therapies targeting these checkpoint molecules have demonstrated significant clinical benefits. This is because antibody-based IC inhibitors and a variety of specific small molecule inhibitors can inhibit key oncogenic signaling pathways and induce durable tumor remission in patients with a variety of cancers. Deciphering the roles and regulatory mechanisms of these IC molecules will provide crucial theoretical guidance for clinical treatment. In this review, we summarize the current knowledge on the functional and regulatory mechanisms of these IC molecules at multiple levels, including epigenetic regulation, transcriptional regulation, and post-translational modifications. In addition, we provide a summary of the medications targeting various nodes in the regulatory pathway, and highlight the potential of newly identified IC molecules, focusing on their potential implications for cancer diagnostics and immunotherapy.
Apoptosis Regulatory Proteins ; CTLA-4 Antigen/therapeutic use* ; Epigenesis, Genetic ; Humans ; Immunotherapy ; Neoplasms/therapy* ; Programmed Cell Death 1 Receptor/therapeutic use*