ABSTRACT
NFY-C, a subunit of the transcription factor NFY, binds to the promoters of several eukaryotic genes, including cell cycle-related genes. RORA is a steroid hormone receptor implicated in a range of important cellular processes. We evaluated the expression of NFY-C and RORA in colorectal adenocarcinomas and normal colonic tissue. NFY-C expression was elevated in adenocarcinomas. Moreover, NFY-C mRNA levels correlated with time to disease progression, while NFY-C protein expression was significantly higher in metastatic disease. RORA expression was downregulated in CRC adenocarcinomas compared to normal controls and correlated with time to disease progression. The role of NFY-C and RORA in CRC merits further investigation.
Subject(s)
Adenocarcinoma/genetics , CCAAT-Binding Factor/genetics , Colorectal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Nuclear Receptor Subfamily 1, Group F, Member 1/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Aged , CCAAT-Binding Factor/analysis , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Disease Progression , Female , Gene Expression Profiling , Humans , Immunohistochemistry , Male , Neoplasm Staging , Nuclear Receptor Subfamily 1, Group F, Member 1/analysis , RNA, Messenger/analysis , RNA, Messenger/genetics , Real-Time Polymerase Chain ReactionABSTRACT
The prion protein, PrP(C), is known mostly for its involvement in neurodegenerative spongiform encephalopathies. However, a role for this molecule in cancer is becoming increasingly recognized partly because it promotes cell proliferation and inhibits apoptosis. Moreover, the codon 129 polymorphism (M129V) of the PRNP gene (the PrP(C)-encoding gene) has been associated with neurodegenerative disease development and severity, while no information is available regarding its role in colorectal cancer (CRC) incidence and disease progression. We have previously reported that expression levels of PRNP may have a prognostic value in CRC, suggesting a role for the prion protein in CRC. The aim of this study was to investigate retrospectively the possible role of M129V and PrP(C) expression in patients with CRC. The M129V single nucleotide polymorphism was genotyped by real time polymerase chain reactions in 110 patients with CRC and 124 healthy donors. Moreover, protein expression was assessed by immunohistochemistry in 68 patients with CRC. Allele frequencies were similar in patients and healthy controls indicating that the M129V polymorphism is not a risk factor for CRC. Furthermore, it did not correlate with any clinicopathological parameters. By contrast, PrP(C) expression was highly elevated in neoplastic compared to normal tissue and differed depending on the primary site. Interestingly, protein levels were correlated with disease recurrence (P = 0.007). Conclusively, PrP(C) overexpression may constitute a prognostic marker for disease recurrence and potentially a new target for anticancer therapy. However, further studies are needed to evaluate prospectively the role of PrP(C) expression in patients with CRC.
Subject(s)
Colorectal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Polymorphism, Single Nucleotide , PrPC Proteins/genetics , Adult , Aged , Aged, 80 and over , Female , Gene Frequency , Genotype , Humans , Male , Middle Aged , RNA, Messenger/genetics , Retrospective StudiesABSTRACT
BACKGROUND: The aim of this study was to determine the prevalence of occult hepatitis B infection in hemodialysis patients with chronic HCV infection and to compare it with that of HCV-infected patients with normal renal function. METHODS: Forty-nine patients on maintenance hemodialysis and 48 HCV-infected but otherwise normal patients, both groups HCV RNA-positive and HBsAg-negative and matched for age and sex, were evaluated for the presence of HBV DNA in serum by polymerase chain reaction (PCR). A proportion of patients (11/49 and 39/48, respectively) were also examined for HBV antigens in hepatocytes by immunohistochemistry. RESULTS: HBV DNA was detected by PCR in 10/49 (20.4%) hemodialysis patients and in 3/48 (6.3%) patients with normal renal function (p=0.041). HBV DNA concentrations were low (<10 3 copies/mL) in both groups. HBV DNA-positive hemodialysis patients had a significantly lower prevalence of past HBV vaccination and lower anti-HBs titers in serum than HBV DNA-negative patients of the same group. No positive staining for HBsAg or HbcAg was observed in the liver biopsies of either group. CONCLUSIONS: Occult HBV infection is more frequent in HCV-infected hemodialysis patients than otherwise normal patients with chronic HCV infection, probably because of impaired immune function in uremic patients and high risk of parenteral exposure to HBV. The clinical significance of this finding is unknown, but HBV vaccination of hemodialysis patients and staff could be an effective way of limiting the risk of transmission of HBV infection within dialysis units.
