PURPOSE: PRV1 (geneID 020406, NB1, CD177) is a gene known to be over-expressed in patients with polycythemia vera. Some evidence suggests an association with sepsis as well. The systemic inflammatory response (SIRS) has many etiologies including, but not limited to sepsis. We conducted this study to evaluate gene expression differences between SIRS patients who develop sepsis compared to uninfected SIRS patients. Patients with evolving sepsis should manifest changes in gene expression, including PRV1, prior to clinical diagnosis as compared to patients with uninfected SIRS.
METHODS: Critically ill, uninfected SIRS patients were prospectively evaluated for development of sepsis. Patients admitted to an intensive care unit were prospectively divided into two groups: 1)Pre-septic SIRS(n=45): SIRS patients who developed clinical sepsis, and 2) Uninfected SIRS(n=45): SIRS patients remaining uninfected. Uninfected SIRS patients were time-matched to pre-septic SIRS patients. Isolated whole blood RNA from 1 day, 2 days, and 3 days (T-12, 36, and 60 hours) prior to clinical sepsis, and day of study entry was analyzed with Affymetrix Hg_U133 2.0 Plus microarrays. Significance criteria required >1.2 fold change in expression between groups and p<0.05 on univariate analysis controlled for multiple comparisons. RT-PCR was then used as confirmatory testing.
RESULTS: Patients were well matched for APACHE II, age, and gender. 12,782 of 54,613(23.4%) probes were differentially expressed between groups at T-36 and T-12. Of these, 3665 (14.9%) probes corresponding to 1735 unique gene ID's demonstrated >1.2 fold change and 76 probes corresponding to 58 unique gene ID's demonstrated greater than 2 fold change. PRV1 (probe 219669_at) demonstrated a 4.72 fold median increased expression at T-36 and a 7.07 fold median increase in expression at T-12 compared to uninfected SIRS. Confirmatory RT-PCR demonstrated a 12.5 fold increase in expression of PRV1 at T-12.
CONCLUSION: PRV1 is significantly differentially expressed up to 2 days prior to the onset of clinical sepsis as compared to uninfected SIRS patients.
CLINICAL IMPLICATIONS: Identifying differential markers between uninfected and septic SIRS patients may allow earlier diagnosis in the intensive care unit.
DISCLOSURE: Matthew Lissauer, Grant monies (from industry related sources) This research was sponsored by an ongoing educational grant from BD diagnostic systems, Sparks, Maryland of which Craig Whitemore, James Garrett, and Richard Moore are full-time employees.