Lipidomic Profiling Reveals Biological Differences between Tumors of Self-Identified African Americans and Non-Hispanic Whites with Cancer

SIMPLE SUMMARY: In human cancers, there are molecular changes associated with their development and responses to therapy. These include changes in molecules in their membranes called sphingolipids. Understanding why and how these lipids are altered may lead to new therapies targeting these changes. Unfortunately, as in other areas of modern cancer research, we lack an understanding of how these molecules are altered in tumors of Black Americans, or whether these changes have different impacts than in White Americans. As an important first step, we used mass spectrometry to profile the sphingolipids in tumors of the colon, liver, lung, head and neck, and endometrial cancers of Black and White Americans. We found that sphingolipids with known roles in how tumors grow and respond to therapy are differentially altered in Black and White Americans. These results strongly support further research designed to determine if Black Americans may benefit from therapies that target these alterations. ABSTRACT: In the US, the incidence and mortality of many cancers are disproportionately higher in African Americans (AA). Yet, AA remain poorly represented in molecular studies investigating the roles that biological factors might play in the development, progression, and outcomes of many cancers. Given that sphingolipids, key components of mammalian cellular membranes, have well-established roles in the etiology of cancer progression, malignancy, and responses to therapy, we conducted a robust mass spectrometry analysis of sphingolipids in normal adjacent uninvolved tissues and tumors of self-identified AA and non-Hispanic White (NHW) males with cancers of the lung, colon, liver, and head and neck and of self-identified AA and NHW females with endometrial cancer. In these cancers, AA have worse outcomes than NHW. The goal of our study was to identify biological candidates to be evaluated in future preclinical studies targeting race-specific alterations in the cancers of AA. We have identified that various sphingolipids are altered in race-specific patterns, but more importantly, the ratios of 24- to 16-carbon fatty acyl chain-length ceramides and glucosylceramides are higher in the tumors of AA. As there is evidence that ceramides with 24-carbon fatty acid chain length promote cellular survival and proliferation, whereas 16-carbon chain length promote apoptosis, these results provide important support for future studies tailored to evaluate the potential roles these differences may play in the outcomes of AA with cancer.