Lysyl-tRNA Synthetase (KRS) Expression in Gastric Carcinoma and Tumor-Associated Inflammation

Background

Lysyl-tRNA synthetase (KRS) is an aminoacyl-tRNA synthetase (ARS) that is essential for protein synthesis during ligation of specific amino acids to their cognate tRNAs. Aberrant expression of ARSs is associated with various human cancers.

Methods

Using immunohistochemical detection, the present study analyzed the clinical relevance of KRS expression in tumor cells and tumor-associated inflammatory cells (TAI) in 457 patients who underwent curative radical surgery and standard adjuvant therapy and who were observed on long-term follow-up.

Results

High expression of KRS in tumor cells (tumor–KRS(+)) was noted in 43.3 % (198 of 457) of cases. High expression of KRS in tumor-associated inflammatory cells (TAI–KRS(+)) including macrophages/monocytes, CD4-positive T cells, and/or neutrophils was observed in 37.2 % (170 of 457) of cases. Status of KRS in the tumor and TAI revealed an association with the known clinicopathological parameters for prognosis of gastric cancer. Tumor–KRS(+) status correlated to shorter overall survival, especially in stage III to IV cancers (P = 0.003), while TAI–KRS(+) status correlated significantly to longer overall survival in gastric cancer (P = 0.049). Cases with tumor–KRS(+) and TAI–KRS(?) status showed significantly reduced survival rates compared to those of other cases (P = 0.010), and status of tumor–KRS(+) and TAI–KRS(?) was revealed as an independently poor prognostic factor of overall survival (P = 0.001).

Conclusions

KRS-related inflammation can be identified in a subset of gastric cancer. This may be a possible mechanism of immune surveillance against tumor progression. In addition, expression status of KRS in tumor and TAI may be an independent prognostic marker for gastric cancer patients.     

Autosomal linkage analysis for cannabis use behaviors in Australian adults

Cannabis is the most commonly used illicit drug in developed and in developing nations. Twin studies have highlighted the role of genetic influences on early stages of cannabis use, such as a lifetime history of use, early-onset use and frequent use, however, we are not aware of any genomic studies that have examined these phenotypes. Using data on 2314 families consisting of 5600 adult Australian offspring and their parents, all of whom were scanned using 1399 unique autosomal markers, we conducted autosomal linkage analyses for lifetime history of cannabis initiation, early-onset cannabis use and frequency of use, using a variance components approach in the linkage package MERLIN. Suggestive evidence for linkage was found on chromosome 18 (LOD 2.14 for frequency of use, LOD 1.97 for initiation, at 90-97 cM) and also on chromosome 19 (LOD 1.92 for early-onset at 17 cM). These LOD scores did not meet genome-wide significance. Further replication of these linkage regions in other samples will be required, although these initial results suggest further targeted efforts on chromosome 18 may yield interesting candidate genes for early stages of cannabis-related behaviors.     

HLA-DRB1*1502 allele,subtype of DR15, is associated with susceptibility to ulcerative colitis and its progression

HLA-DRB1 allele typing was performed by the PCR-RFLP method on 59 ulcerative colitis (UC) patients and 136 healthy controls. Phenotypic frequencies of HLA-B52 and DR2 were significantly increased among the UC patients, serologically. DNA typing of HLA-DRB1 revealed that the genotypic frequency of DRB1*1502 was higher in UC than in the controls (49.2% vs 17.6%;P<0.0001). In the analysis of clinical parameters, 82.8% of patients bearing DRB1*1502 were treated with corticosteroids. DRB1*1501 and DRB1*1502 differ in only one amino acid at residue 86 (valine vs glycine), and 66% of the UC patients carried two glycines at position 86 in the HLA-DR-chain (vs 51% of control;P<0.05). These observations suggest that the presence of Gly-86 in the HLA-chain and surrounding amino acid sequence of HLA-DRB1*1502 is strongly associated with susceptibility to UC.     

Cytosol intermediates in the transport of iron

Three 59Fe-labeled nonheme components of the cytosol were identified when rabbit reticuloyctes were incubated with 59Fe-labeled plasma under conditions in which the iron supply was not limiting. Two of these components were identified as ferritin and transferrin. The latter was characterized by gel filtration as having apparent molecular weight higher than transferrin, indicating that the transferrin may be complexed to another moiety. The third component, referred to as iron- binding protein-I (IBP-I), is as yet uncharacterized. When the reticulocytes were incubated with unlabeled plasma after pulse-labeling with 59Fe-labeled plasma, 59Fe radioactivity in these cytosol components decreased; after 15 min of chase, the 59Fe in ferritin, transferrin, and IBP-I fell to 64.6%, 26.5%, and 65.8% of the initial values, respectively. A good correlation existed between the decrease of 59Fe in these three nonheme compartments and the associated increase in 59Fe-heme. The data presented suggest that cytosol ferritin, transferrin, and IBP-I are intermediates in the transport of 59Fe from the plasma membrane to the mitochondria.