Study Suggests Racial Differences in Lung Tumor Biology

Key Points

  • Comparative transcriptomic profiling revealed clear differences in lung tumor biology between African American and European American patients with non–small cell lung cancer.
  • On the basis of predicted drug resistance to adjuvant chemotherapies, African American patients may not benefit equally from the same clinical drugs as European American patients.

According to research by the American Cancer Society, lung cancer is the second most common cancer in men and women in the United States and is the leading cause of cancer-related death. In addition, among all populations, African Americans tend to have the highest lung cancer incidence and mortality rates of any other group. Now, a study examining the etiologic differences in tumor biology may shed light on the cause of lung cancer disparities between African Americans and other ethnic groups.

The study by Mitchell et al investigated whether racial differences in gene and miRNA expression translate to differences in lung tumor biology, with clinical relevance in African Americans and European Americans. They has found that race-enriched gene and miRNA expression signatures suggest a more aggressive disease in African Americans. The findings provide a rationale for integrating coding and noncoding transcriptome profiles, along with clinical, demographic, and genomic data, when determining treatment options. The study was published in Clinical Cancer Research.

Study Methodology

The researchers analyzed normal tissue and non–small cell lung cancer (NSCLC) tissue obtained from 64 African Americans and 74 European Americans during surgery to remove their lung tumors. The patients were enrolled in the NCI-Maryland Case Control Study between 1998 and 2014. Tissue from 22 AAs and 19 EAs was analyzed for mRNA expression and tissue from 42 African Americans and 55 EAs was analyzed for microRNA expression.

Pathway enrichment, predicted drug response, tumor microenvironment infiltration, cancer immunotherapy antigen profiling, and miRNA target enrichment were assessed.

Study Findings

The researchers found that African American-enriched differential gene expression was characterized by stem cell and invasion pathways. Differential gene expression in lung tumors from European Americans was primarily characterized by cell proliferation pathways. Population-specific gene expression was partly driven by population-specific miRNA expression profiles.

Drug susceptibility predictions revealed a strong inverse correlation between African American resistance and European American sensitivity to the same panel of drugs. Statistically significant differences in M1 and M2 macrophage infiltration were observed in African Americans (P < .05); however, expression of programmed cell death ligands 1 and 2 was similar between both.

“Taken together, our data have shown African Americans and European Americans with NSCLC are likely to diverge in potentially clinically meaningful ways.... Predicted drug sensitivity and resistance analysis suggested that African Americans and European Americans may not equally benefit from the same range of clinical (current) and preclinical (future) drugs. We also identified racial differences in the abundance and composition of infiltrating immune cells from the lung tumor microenvironment, which must be considered, as cancer immunotherapy is rapidly moving toward being a standard of care. Leveraging transcriptomic differences, along with integrative genomics, in NSCLCs from African Americans and European Americans has important implications for combinatorial therapeutic interventions based on population differences in tumor biology. Understanding the racial differences in lung tumor biology between African Americans and European Americans, and accounting for its contribution to therapeutic response, could ultimately help to reduce morbidity and mortality in both populations,” concluded the study authors.

Brid M. Ryan, PhD, MPH, of the National Cancer Institute, is the corresponding author of this study.

Funding for this study was provided by the National Institutes of Health.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.