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Circulating histocompatibility antigen (HLA) gene products may help differentiate benign from malignant indeterminate pulmonary lesions
Authors:Smriti Kanangat  Christopher W. Seder  Melissa R. Pergande  Gabriela C. Lobato  Cristina L. Fhied  Maryam F. Raouf  Michael J. Liptay  Jeffrey A. Borgia
Affiliation:1. Department of Biochemistry, United States;2. Department of Cardiovascular and Thoracic Surgery, United States;3. Department of Pathology, United States;4. Department of Cell & Molecular Medicine, Rush University Medical Center, Chicago, IL 60612, United States
Abstract:

Background

This study explores the potential diagnostic utility of soluble Human Leukocyte Antigen (sHLA) molecules differentially released by lung adenocarcinoma and benign lung lesions.

Methods

Conditioned media from the NSCLC cell lines H358 and H1703 were immunoblotted for soluble isoforms of major histocompatibility complex (MHC) class I (ABC) and II (DRB1, DMB, and DQ) antigens. Sera from 25 patients with benign and 25 patients with malignant lesions were similarly evaluated to appraise the potential diagnostic value.

Results

Higher concentrations of soluble HLA class I molecules were observed in conditioned medium for the highly-invasive H1703 cell line, relative to the more indolent H358 cells. Evaluation of these markers against a cohort of 50 cases demonstrated that patients with malignant lesions possess higher levels of HLA class I and II molecules relative to those with benign lesions (p??0.75) for DMB and the 26?kDa isoform of DQ in distinguishing lesion pathology.

Conclusions

Soluble HLA molecules may have diagnostic value for early-stage NSCLC. Validation studies are currently underway using sera from a lung cancer screening cohort.
Keywords:NSCLC  non-small cell lung cancer  HLA  human leukocyte antigens  LDCT  low-dose computed tomography  MHC  major histocompatibility complex  ATCC  American Type Culture Collection  RPMI  Roswell Park Memorial Park  SDS-PAGE  standard denaturing polyacrylamide gel electrophoresis  LOH  loss of heterozygosity  NSCLC  HLA  Biomarker  Screening  Nodule
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