Decreased PCSK9 expression in human hepatocellular carcinoma.

BACKGROUND: The management of hepatocellular carcinoma (HCC) is limited by the lack of adequate screening biomarkers and chemotherapy. In response, there has been much interest in tumor metabolism as a therapeutic target. PCSK9 stimulates internalization of the LDL-receptor, decreases cholesterol uptake into hepatocytes and affects liver regeneration. Thus, we investigated whether PCSK9 expression is altered in HCC, influencing its ability to harness cholesterol metabolism. METHODS: Thirty-nine patients undergoing partial hepatectomy or liver transplantation for HCC were consented for use of HCC tissue to construct a tissue microarray (TMA). The TMA was immunostained for PCSK9. Imagescope software was used to objectively determine staining, and assess for pathological and clinical correlations. PCSK9 and LDL receptor mRNA levels in flash-frozen HCC and adjacent liver tissue were determined by quantitative RT-PCR. Serum PCSK9 levels were determined by ELISA. RESULTS: By immunohistochemistry, there was significantly lower expression of PCSK9 in HCC as compared to adjacent cirrhosis (p-value < 0.0001, wilcoxon signed-rank test). Significantly greater staining of PCSK9 was present in cirrhosis compared to HCC (p value <0.0001), and positivity (percentage of positive cells) was significantly greater in cirrhosis compared to HCC (p-value < 0.0001). Conversely, significantly higher expression of LDL-R was present in HCC as compared to the adjacent cirrhosis (p-value < 0.0001). There was no significant correlation of PCSK9 staining with grade of tumor, but there were significant correlations between PCSK9 staining and stage of fibrosis, according to spearman correlation test. PCSK9 mRNA levels were relatively less abundant within HCC compared to adjacent liver tissue (p-value =0.08) and normal control tissue (p-value =0.02). In contrast, serum PCSK9 levels were significantly increased among patients with HCC compared to those with chronic liver disease without HCC (p-value =0.029). LDL receptor mRNA was consistantly greater in HCC when compared to normal control tissue (p-value = 0.06) and, in general, was significantly greater in HCC when compared to adjacent liver (p-value = 0.04). CONCLUSIONS: The decreased expression of PCSK9 and conversely increased LDL-R expression in HCC suggests that HCC modulates its local microenvironment to enable a constant energy supply. Larger-scale studies should be conducted to determine whether PCSK9 could be a therapeutic target for HCC.

Percutaneous US-guided renal biopsy: a retrospective study comparing the 16-gauge end-cut and 14-gauge side-notch needles.

PURPOSE: Assess glomerular yield and safety profile of two different types of needles for percutaneous ultrasound-guided kidney biopsy. MATERIALS AND METHODS: Over 24 months, 121 ultrasonographic ultrasound-guided renal biopsies were performed on native kidneys of 121 adults: 66 with 16-gauge, 29-mm end-cut (BioPince) needles and 55 with 14-gauge, 1.9-mm side-notch (Tru-Cut) needles. RESULTS: The mean number of complete glomeruli harvested per biopsy was 21.0 and 19.3, respectively, and the mean number of core samples required to obtain a satisfactory biopsy was 1.8 and 2.6, respectively. The ratio of glomeruli harvested to core samples needed with the end-cut needle was 58% greater than that with the side-notch needles (11.7 vs 7.4, respectively; difference of 4.3; 95% confidence interval: 2.0, 6.8). Procedures performed with end-cut needles were associated with fewer major complications (1.5% vs 7.3% with side-notch needles). CONCLUSIONS: Compared to the 14-g Tru-cut needle, the 16-g end-cut needle provided better glomerular yield per core sample, required fewer cores for satisfactory tissue specimen, and resulted in fewer major complications.