Identification of CD37, cystatin A, and IL-23A gene expression in association with brain metastasis: analysis of a prospective trial

Abstract

Purpose/Objectives: We aimed to assess the predictive value of a lung cancer gene panel for the development of brain metastases. Materials/Methods: Between 2011 and 2015, 102 patients with lung cancer were prospectively enrolled in a clinical trial in which a diagnostic fine-needle aspirate was obtained. Gene expression was conducted on all samples that rendered a diagnosis of non-small cell lung cancer (NSCLC). Subsequent retrospective analysis of brain metastases-related outcomes was performed by reviewing patient electronic medical records. A competing risk multivariable regression was performed to estimate the adjusted hazard ratio for the development of brain metastases and non-brain metastases from NSCLC. Results: A total of 49 of 102 patients had died by the last follow-up. Median time of follow-up was 13 months (range 0.23-67 months). A total of 17 patients developed brain metastases. Median survival time after diagnosis of brain metastases was 3.58 months (95% confidence interval (CI) 2.17, not available). A total of 30 patients developed metastases without any evidence of brain metastases until the time of death or last follow-up. Competing risk analysis identified three genes that were downregulated differentially in the patients with brain metastases versus non-brain metastatic disease: CD37 (0.017), cystatin A (0.022), and IL-23A (0.027). Other factors associated with brain metastases include: stage T (P ⩽ 8.3e-6) and stage N (P= 6.8e-4). Conclusions: We have identified three genes, CD37, cystatin A, and IL-23A, for which downregulation of gene expression was associated with a greater propensity for developing brain metastases. Validation of these biomarkers could have implications on surveillance patterns in patients with brain metastases from NSCLC.

CD37 in B Cell Derived Tumors—More than Just a Docking Point for Monoclonal Antibodies

“…Interestingly, the very recent observations from non-small cell lung cancer (NSCLC) have suggested low expression of CD37 as a marker of metastasis. Gene expression profiling from fine-needle aspirates from NSCLC tumors has identified CD37 as one of three genes downregulated in the course of the disease progression [ 53 ]. Recent advances in tumor immunology demonstrate that tumor-infiltrating B cells influence tumor progression through the productions of antibodies, immunosuppressive cytokines such as IL-10, as well as by interacting with other immune cells [ 45 ].…”

Multi-Omics Analysis of Brain Metastasis Outcomes Following Craniotomy

“…Dohm et al. evaluated RNA-seq data from patients who underwent fine needle aspiration for newly diagnosed non-small cell lung cancer ( 36 ). These patients were subsequently followed over the natural history of their disease and the genomics of patients who developed brain metastases were compared to those who did not develop brain metastases.…”

Tumor-infiltrating immune cell activated memory CD4+ T cells predicts prognosis in gastric cancer

“…At the same time, our research found that IL23A was closely related to the development and prognosis of gastric cancer. Interaction between IL23 and macrophages has a significant impact on the immunotherapy of cancer [18,19]. Blogowski showed that patients with all types of gastric neoplasms have significantly lower IL23A levels [20].…”