Circulating histocompatibility antigen (HLA) gene products may help differentiate benign from malignant indeterminate pulmonary lesions

Hum Immunol. 2018 Jul;79(7):558-563. doi: 10.1016/j.humimm.2018.04.003. Epub 2018 Apr 12.


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 < 0.05), with exception to the primary isoform, DQA1, which was suppressed in malignancies. An analysis of biomarker performance via ROC analysis revealed promising performance (AUC > 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: Biomarker; HLA; NSCLC; Nodule; Screening.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Cell Line, Tumor
  • Cohort Studies
  • Diagnosis, Differential
  • Early Detection of Cancer
  • Female
  • HLA Antigens / blood*
  • Histocompatibility Antigens Class I / blood*
  • Histocompatibility Antigens Class II / blood*
  • Humans
  • Lung Neoplasms / diagnosis*
  • Male
  • Middle Aged
  • Multiple Pulmonary Nodules / diagnosis*
  • Sensitivity and Specificity


  • Biomarkers, Tumor
  • HLA Antigens
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II