Aim
To assess kallikrein (
KLK
) expression in recurrent and non-recurrent prostate tumors and adjacent healthy prostate tissues.
Methods
The expression levels of 15
KLK
genes in 34 recurrent and 36 non-recurrent prostate cancer samples and 19 adjacent healthy prostate tissue samples was assessed with quantitative reverse-transcription polymerase chain reaction. The samples were obtained from Baylor College of Medicine, Houston, TX, USA between 2013 and 2016 .
Results
Compared with controls, prostate cancer samples showed a strong decrease in
KLK1, KLK4, KLK9,
and
KLK14
. Recurrent samples were negative for
KLK1
,
KLK2,
and
KLK14
but demonstrated higher levels of
KLK3, KLK4,
and
KLK9
than controls. Other
KLK
s were not significantly expressed.
Conclusion
This study for the first time showed a difference in the expression levels of the
KLK
gene family in recurrent prostate cancer.
KLK
s could be used as recurrence markers for prostate cancer.
Background
Due to the growing evidence of the importance of iron status in immune responses, the biomarkers of iron metabolism are of interest in novel Coronavirus Disease 2019 (COVID-19). The present prospective study was carried out to compare iron status indicated by levels of ferritin with the levels of two novel biomarkers related to iron homeostasis, hephaestin and hypoxia-inducible factors-1 (HIF-1α) in the serum of patients with COVID-19 in comparison with a control group.
Methods and results
Blood samples from 34 COVID-19 patients and from 43 healthy volunteers were collected and the levels of HEPH and HIF-1α were measured by ELISA and compared with levels of serum ferritin. COVID-19 patients had higher serum levels of ferritin than those levels in control group (P < 0.0001). Conversely levels of HIF-1α and HEPH in the COVID-19 group were significantly lower than those of control group (P < 0.0001 for both). An inverse correlation between hephaestin and ferritin as well as between HIF-1α and ferritin was found among all subjects (P < 0.0001), and among COVID-19 patients, but not to statistical significance.
Conclusion
Levels of hephaestin and HIF-1α were found to be inversely related levels of ferritin across all participants in the study, and to our knowledge this is the first report of hephaestin and HIF-1α as potential markers of iron status. Further studies are needed to corroborate the findings, utilizing a broader range of markers to monitor inflammatory as well as iron status.
Hephaestin (Hp) is a trans-membrane protein, which plays a critical role in intestinal iron absorption. Hp was originally identified as the gene responsible for the phenotype of sex-linked anaemia in the sla mouse. The mutation in the sla protein causes ac-cumulation of dietary iron in duodenal cells, causing severe microcytic hypochromic anaemia. Although mucosal uptake of dietary iron is normal, export from the duodenum is inhibited. Hp is homologous to ceruloplasmin (Cp), a member of the family of multi copper fer-roxidases (MCFs) and possesses ferroxidase activity that facilitates iron release from the duodenum and load onto the serum iron trans-port protein transferrin. In the present study, attempts were made to produce biologically active recombinant mouse hephaestin as a secretory form tagged with green fluorescent protein (GFP), Hpsec-GFP. Plasmid expressing Hpsec-GFP was constructed and transfected into COS and CHO cells. The GFP aided the monitoring expression in real time to select the best conditions to maximise expression and provided a tag for purifying and analysing Hpsec-GFP. The protein had detectable oxidase activity as shown by in-gel and solution-based assays. The methods described here can provide the basis for further work to probe the interaction of hephaestin with other proteins using complementary fluorescent tags on target proteins that would facilitate the fluorescence resonance energy transfer measurements, for example with transferrin or colocalisation studies, and help to discover more about hephaestin works at the molecular level.
Prostate cancer has been found to be the most life-threatening disease among men all over the world, given its wide occurrence and partially-successful therapies associated with a high rate of mortality. Thus, meticulous analysis of this cancer and its characteristics, including molecular biology, epigenetic mechanisms and markers during tumor development, may provide the scientists with valuable insights to design the therapeutic protocol with improved efficiency and low rate of failure and limited further side effects, such as infertility. Moreover, the risk associated with the current invasive procedures on prostate cancer patients has prompted researchers to invest effort in the discovery of being less-invasive and more advantageous procedures based on the patient's own physiological and anatomical characteristics. This paper reviews past and present studies on epigenetics and molecular markers of prostate cancer, as well as the designed therapies. Additionally, we present a future vision and prospect of the current treatments.
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