Chun Pu

Quantification of plasma cell-free DNA in predicting therapeutic efficacy of sorafenib on metastatic clear cell renal cell carcinoma.

PURPOSE: The objective of this study is to determine whether or not plasma cfDNA levels can predict efficacy of sorafenib in patient with metastatic cRCC. MATERIALS AND METHODS: Plasma cfDNA levels were quantified by quantitative real-time PCR at six different time-points (before treatment, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and 24 weeks) in 18 metastatic cRCC patients receiving sorafenib, as assessed by CT examination according to RECIST 1.1. RESULTS: A significantly lower plasma cfDNA level, measured from 8 weeks to 24 weeks, was found in patients with remission or stable disease than in those with progression. Higher levels in plasma cfDNA levels during the course of treatment indicated poor outcome. For predicting progression, a sensitivity of 66.7% was achieved at 100% specificity using cfDNA levels at 8 weeks. CONCLUSIONS: Monitoring of plasma cfDNA levels during the course of sorafenib therapy could identify metastatic cRCC patients who are likely to exhibit a poor response at an early stage.

Apolipoprotein M: Research progress, regulation and metabolic functions (Review)

Apolipoprotein M (ApoM) is a novel lipoprotein-associated plasma protein of the apolipoprotein family. It is predominantly enriched in high-density lipoprotein (HDL), and is also present in small quantities in low-density lipoprotein (LDL) and in very low-density lipoprotein. Transgenic animal experiments have suggested that ApoM can be transformed into various lipoproteins and may be involved in lipoprotein metabolism. ApoM has five subtypes, however, their biological functions remain to be elucidated. The α-helix, formed by ApoM through hydrophobic signal peptides, is anchored to the phospholipid monomolecular layers of HDL. Hydrophobic domains can associate with small lipophilic ligands and perform biological functions. ApoM may affect HDL metabolism and exhibit anti-atherosclerotic functions. Human HDL, containing ApoM subfractions, can protect LDL from oxidation and regulate cholesterol efflux more effectively than HDL without ApoM. Therefore, it is highly correlated with plasma cholesterol levels in the human body. Although previous studies have reported no difference in ApoM between groups of patients with coronary heart disease (CHD) and a normal control groups, the anti-atherosclerotic effect of ApoM is evident. ApoM is highly expressed in renal proximal tubule cells and is secreted into the urine in tubule cells. However, it is usually reabsorbed by giantin-associated proteins in a process, which is also affected in kidney disease. In addition to liver and kidney cells, low expression levels of ApoM occur in the intestinal tract and are associated with lymph node metastasis of colorectal cancer. ApoM gene polymorphism is associated with CHD, diabetes and other immune-associated diseases. Investigations into the gene regulation of ApoM may assist in further clarifying the role of ApoM in blood glucose and lipid metabolism. Genetic modification of the mouse ApoM gene is an essential technique to investigate the gene expression and regulation of ApoM, and to clarify the potential roles of ApoM in lipoprotein metabolism, atherosclerosis, diabetes and renal diseases.

Quantification of peripheral blood CD133 mRNA in identifying metastasis and in predicting recurrence of patients with clear cell renal cell carcinoma.

OBJECTIVES To investigate whether CD133 messenger ribonucleic acid (mRNA) could provide useful information to identify metastasis or predict recurrence in patients with clear cell renal cell carcinoma (cRCC). METHODS AND MATERIALS This study included 86 patients with cRCC and 30 healthy controls. Real-time reverse transcriptase-polymerase chain reaction was used to quantify CD133 mRNA in peripheral blood mononuclear cells before nephrectomy. RESULTS The average CD133 mRNA in patients with metastatic cRCC (1.546 ± 0.291) was significantly higher than that in those with localized cRCC (1.034 ± 0.316, P = 0.022) or in controls (0.042 ± 0.028, P = 0.001). Metastasis could be identified with a sensitivity of 82.6% at specificity of 69.8% by CD133 mRNA. Among patients with localized cRCC, there was a significant difference in CD133 mRNA between the patients with recurrence (1.136 ± 0.127) and without recurrence (1.010 ± 0.091, P = 0.047). Recurrence could be identified with a sensitivity of 75.0% at specificity of 61.8%. Patients with a higher CD133 mRNA had a significantly higher recurrence rate than those with a low CD133 mRNA (P = 0.019). CONCLUSIONS CD133 mRNA can be useful for identifying metastasis, predicting recurrence, and stratifying the patients into different risk groups for possible adjuvant treatment.

ApoM/HDL-C and apoM/apoA-I ratios are indicators of diabetic nephropathy in healthy controls and type 2 diabetes mellitus.

BACKGROUND Apolipoprotein M (apoM) concentrations were decreased in type 2 diabetes mellitus (T2DM). ApoM was selectively expressed in renal tubular epithelial cells. We investigated the changes in plasma apoM concentrations in diabetic nephropathy (DN) patients and the potential of apoM as a biomarker of DN. METHODS A total of 96 DN patients and 100 age- and sex-matched diabetic non-nephropathy (non-DN) patients and 110 healthy controls were included. All T2DM patients were divided into 3 groups according to urinary albumin excretion: normoalbuminuria (n=100), microalbuminuria (n=50) and macroalbuminuria (n=46). Plasma apoM concentrations were measured by enzyme-linked immunosorbent assay. RESULTS DN Patients had higher plasma apoM concentrations than those in non-DN patients (22.23±11.69 vs. 18.96±7.85ng/μl, P<0.05). In addition, microalbuminuria group showed higher plasma apoM concentrations than those in normoalbuminuria group (22.67±11.40 vs. 18.96±7.85ng/μl, P<0.05). The areas under curve (AUC) of apoM using a receiver-operating characteristic (ROC) curve analysis showed that plasma apoM concentrations were not indicators for identification of DN from healthy people (AUC=0.478, P=0.585) and from T2DM (AUC=0.563, P=0.125). DN patients had higher ratios of apoM/HDL-C and apoM/apoA1 than those in healthy controls and in non-DN patients. ApoM/HDL-C and apoM/apoA1 ratios could be used as indicators for identification of DN from healthy people (AUC=0.597, P=0.016; AUC=0.665, P=0.000, respectively) and from T2DM (AUC=0.580, P=0.050; AUC=0.601, P=0.015, respectively). CONCLUSIONS ApoM/HDL-C and apoM/apoA1 ratios could be used as indicators for identification of DN from healthy people and from T2DM patients.

Methylation of DLEC1 promoter is a predictor for recurrence in Chinese patients with gastric cancer.

Purpose. To investigate promoter methylation in the deleted in lung and esophageal cancer 1 (DLEC1) gene in Chinese patients with gastric cancer. Methods. A total of 227 patients with gastric cancer were enrolled. The methylations of the promoter regions of DLEC1 and ACTB were determined using quantitative methylation-specific PCR. The DLEC1 methylation was compared to the clinicopathological variables of gastric cancer. Results. DLEC1 methylation was not associated with the clinicopathological variables of gastric cancer. Patients with DLEC1-hypermethylated gastric cancer had significantly higher recurrence rate than those with DLEC1-hypomethylated gastric cancer (P = 0.025; hazard ratio = 2.43). Conclusions. Methylation of DELC1 promoter may be a valuable predictor for recurrence in Chinese patients with gastric cancer.

CD146 Promoter Polymorphism (rs3923594) Is Associated with Recurrence of Clear Cell Renal Cell Carcinoma in Chinese Population

Introduction CD146 is a membrane signal receptor in tumor-induced angiogenesis. However, limited studies have focused on the CD146 promoter polymorphisms in clear cell renal cell carcinoma (ccRCC). Purpose The purpose of this study was to investigate the association between polymorphisms located in the promoter region of the CD146 gene and characteristics of ccRCC in Chinese population. The association between the CD146 promoter polymorphisms and CD146 expression was also investigated in ccRCC. Materials and Methods A total of 600 samples including 300 ccRCC patients and 300 healthy controls were collected for analysis of the CD146 promoter polymorphisms by direct sequence. The CD146 expressions were measured by qRT-PCR. Results We had not found any significant differences in genotypic and allelic frequencies of CD146 promoter polymorphisms between ccRCC patients and controls. The rs3923594 was associated with stage and metastasis (300 cases) and recurrence (263 cases) of ccRCC in Chinese population. A significant association was also observed between the rs3923594 and CD146 expression (227 cases) in ccRCC. Conclusions CD146 promoter polymorphisms were not associated with the risk of ccRCC in Chinese population. The rs3923594 was an independent predictor of recurrence in Chinese patients with localized ccRCC.

Serum Extracellular Superoxide Dismutase Is Associated with Diabetic Retinopathy Stage in Chinese Patients with Type 2 Diabetes Mellitus

Extracellular superoxide dismutase (ecSOD) is the major extracellular scavenger of reactive oxygen species and associated with the diabetic complication in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the serum ecSOD activity in Chinese patients with different stages of diabetic retinopathy (DR) and evaluate the association between the serum ecSOD activity and the severity of DR. A total of 343 T2DM patients were categorized into three groups: nondiabetic retinopathy (NDR) group, nonproliferative diabetic retinopathy (NPDR) group, and proliferative diabetic retinopathy (PDR) group. Serum ecSOD activities were measured by the autoxidation of the pyrogallol method. In this study, 271, 46, and 26 patients were enrolled in the NDR, NPDR, and PDR groups, respectively. We found a significantly decreased trend of serum ecSOD activity among NDR subjects (118.0 ± 11.5 U/mL) compared to NPDR subjects (108.5 ± 11.9 U/mL) (P < 0.001) and NPDR subjects compared to PDR subjects (102.7 ± 12.4 U/mL) (P = 0.041). Serum ecSOD activity was an independent risk factor for DR (OR = 0.920, P < 0.001) and was associated with the progression of DR. Serum ecSOD activity might be a biomarker for DR screening and evaluation of the clinical severity of DR in Chinese T2DM patients.

Apolipoprotein status in type 2 diabetes mellitus and its complications (Review)

Dyslipidaemia in type 2 diabetes mellitus (T2DM) is characterized by high plasma triglyceride concentrations, reduced high‑density lipoprotein concentrations and increased small density low‑density lipoprotein concentrations. Dyslipidaemia may lead to cardiovascular disease (CVD) and other complications. Apolipoproteins mainly comprise six species, apolipoprotein (apo)A, apoB, apoC, apoD, apoE and apoM, which are important components of plasma lipoproteins that carry lipids and stabilize the structure of lipoproteins. Complex metabolic disorders of apolipoproteins are present in T2DM, such as high plasma apoB, apoC‑II, apoC‑III and apoE concentrations, and low plasma apoA‑I and apoM concentrations, which are associated with dyslipidaemia and interrelated complications. Plasma concentrations of some apolipoproteins are also altered in T2DM with CVD or other complications. Several apolipoprotein polymorphisms are associated with diabetes susceptibility and/or lipid metabolism. The present review described the metabolic disorders of apolipoproteins in T2DM and its complications, and the relationship between each major apolipoprotein and T2DM, as well as the effects of apolipoprotein polymorphisms on diabetic susceptibility.