Noncoding RNA Differences Found in African Americans with NSCLC

A new study examining non-small cell lung cancer (NSCLC) is demonstrating clear differences in lung tumor biology between African Americans and European Americans based on comparative transcriptomic profiling. Investigators report in Clinical Cancer Research that these findings have clinical relevance for lung cancer patients. The authors call for much greater participation by African Americans in lung cancer clinical trials in order to integrate and leverage transcriptomic differences with other clinical data to maximize therapeutic benefit in both the African American and European American populations.

“Our study is the first to compare the biology of lung cancer between European Americans and African Americans from a gene expression perspective. We found that while there is much shared biology between these populations, there are also some differences,” said study author Brid Ryan, PhD, MPH, who is an investigator in the Laboratory of Human Carcinogenesis at the National Cancer Institute’s Center for Cancer Research in Bethesda, Maryland.

She said much of the revolutionary work that underpins precision medicine has been conducted on populations of European descent. There has been only limited work in minority populations. Ryan and colleagues analyzed normal and NSCLC tissue obtained from 64 African Americans and 74 European Americans during surgery. Tissue from 22 African Americans and 19 European-Americans was analyzed for mRNA expression.

The researchers found that expression of 2,210 genes was more than two-fold increased or decreased in NSCLC from African Americans compared with matched normal tissue. For European American samples, 2,921 genes were differentially expressed by more than two-fold. Many of the genes were differentially expressed between NSCLC and normal tissue in both African Americans and European Americans, but 637 were differentially expressed only in African Americans and 1,844 in European Americans.

The genes differentially expressed only in the African American NSCLC samples were enriched for those involved in stem cell biology and invasive behavior. The genes differentially expressed only in European Americans were enriched for those involved in cell cycle, mitosis, and proliferation.

In addition, the genes differentially expressed only in African Americans or European-Americans were analyzed using a drug-response prediction model called the Connectivity Map. The two gene subsets predicted similar resistance/sensitivity to NSCLC in African Americans and European-Americans to some drugs; for other drugs, the predictions varied by race. The study showed that NSCLC from African Americans was predicted to be resistant to 53 drugs to which NSCLC tumors from European Americans were sensitive. Among these drugs was irinotecan, which is a cytotoxic chemotherapeutic used for treating certain types of cancer.

“Discoveries made through precision medicine approaches have great potential to improve health outcomes. But, we want to make sure that all populations can benefit. Studying the biology of lung cancer in African Americans is one step towards that goal. We want to record the biology, understand it, and then as much as we can leverage it to improve patients’ lung cancer outcomes,” Ryan told OncoTherapy Network.