C77G in PTPRC (CD45) is no risk allele for ovarian cancer, but associated with less aggressive disease
PLOS ONE
Authors: Landskron, Johannes; Kraggerud, Sigrid M.; Wik, Elisabeth; Dorum, Anne; Bjornslett, Merete; Melum, Espen; Helland, Oystein; Bjorge, Line; Lothe, Ragnhild A.; Salvesen, Helga B.; Tasken, Kjetil
Abstract
The pan lymphocyte marker CD45 exists in various isoforms arising from alternative splicing of the exons 4, 5 and 6. While naive T cells express CD45RA translated from an mRNA containing exon 4, exons 4-6 are spliced out to encode the shorter CD45R0 in antigen-experienced effector/memory T cells. The SNP C77G (rs17612648) is located in exon 4 and blocks the exon's differential splicing from the pre-mRNA, enforcing expression of CD45RA. Several studies have linked C77G to autoimmune diseases but lack of validation in other cohorts has left its role elusive. An incidental finding in an ovarian cancer patient cohort from West Norway (Bergen region, n = 312), suggested that the frequency of C77G was higher among ovarian cancer patients than in healthy Norwegians (n = 1,357) (3.0% vs. 1.8% allele frequency). However, this finding could not be validated in a larger patient cohort from South-East Norway (Oslo region, n = 1,198) with 1.2% allele frequency. Hence, C77G is not associated with ovarian cancer in the Norwegian population. However, its frequency was increased in patients with FIGO stage II, endometrioid histology or an age at diagnosis of 60 years or older indicating a possible association with a less aggressive cancer type.
Systematic Multiomic Analysis of Ly75 Gene Expression and Its Prognostic Value through the Infiltration of Natural Killer (NK) Cells in Skin Cutaneous Melanoma
JOURNAL OF CLINICAL MEDICINE
Authors: Gil, Minchan; Kim, Kyung Eun
Abstract
Ly75 (also known as DEC-205 or CD205) is expressed in immune cells and cancers and involved in tumor immunity. However, clinical relevance of Ly75 expression in skin cutaneous melanoma (SKCM) have not been comprehensively studied. This study analyzed the correlation between Ly75 mRNA expression and patient survival using systematic multiomic analysis tools. Ly75 mRNA expression level was significantly lower in SKCM tissues than in normal tissues. Survival analysis showed that Ly75 expression significantly correlated with good patient survival. To determine possible mechanisms, the association between Ly75 expression and immune cell infiltration was analyzed. Ly75 expression was positively correlated with various infiltrated immune cells, particularly with natural killer (NK) cell infiltration and activation in SKCM. Moreover, analysis of Ly75-co-altered gene expression revealed that Ptprc (CD45) was most significantly correlated with Ly75. Gene ontology analysis of Ly75-co-altered genes indicated the relation to lymphocyte activation, including NK cell activation. Overall, our study provides the first clinical evidence that Ly75 expression is significantly associated with melanoma patient survival and NK cell infiltration, suggesting that Ly75 could be a useful prognostic factor.