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BACKGROUND: The incidence and mortality rates of hepatocellular carcinoma (HCC) among Hispanic individuals in the United States are much higher than in non-Hispanic white people. We conducted multi-omics analyses to elucidate molecular alterations in HCC among Hispanic patients. METHODS: Paired tumor and adjacent non-tumor samples were collected from 31 Hispanic HCCs in South Texas (STX-Hispanic) for genomic, transcriptomic, proteomic, and metabolomic profiling. Serum lipids were profiled in 40 Hispanic and non-Hispanic patients with or without clinically diagnosed HCC. RESULTS: Exome sequencing revealed high mutation frequencies of AXIN2 and CTNNB1 in STX Hispanic HCCs, suggesting a predominant activation of the Wnt/ß-catenin pathway. TERT promoter mutations were also significantly more frequent in the Hispanic cohort (Fisher's exact test, p < .05). Cell cycles and liver function were positively and negatively enriched, respectively, with gene set enrichment analysis. Gene sets representing specific liver metabolic pathways were associated with dysregulation of corresponding metabolites. Negative enrichment of liver adipogenesis and lipid metabolism corroborated with a significant reduction in most lipids in serum samples of HCC patients (paired t-test, p < .0001). Two HCC subtypes from our Hispanic cohort were identified and validated with the TCGA liver cancer cohort. Patients with better overall survival showed higher activity of immune and angiogenesis signatures, and lower activity of liver function-related gene signatures. They also had higher levels of immune checkpoint and immune exhaustion markers. CONCLUSIONS: Our study revealed specific molecular features of Hispanic HCC and potential biomarkers for therapeutic management. It provides a unique resource for studying Hispanic HCC.
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Background: The incidence and mortality rates of hepatocellular carcinoma (HCC) among Hispanics in the United States are much higher than those of non-Hispanic whites. We conducted comprehensive multi-omics analyses to understand molecular alterations in HCC among Hispanic patients. Methods: Paired tumor and adjacent non-tumor samples were collected from 31 Hispanic HCC in South Texas (STX-Hispanic) for genomic, transcriptomic, proteomic, and metabolomic profiling. Additionally, serum lipids were profiled in 40 Hispanic and non-Hispanic patients with or without clinically diagnosed HCC. Results: Exome sequencing revealed high mutation frequencies of AXIN2 and CTNNB1 in STX Hispanic HCCs, suggesting a predominant activation of the Wnt/ß-catenin pathway. The TERT promoter mutation frequency was also remarkably high in the Hispanic cohort. Cell cycles and liver functions were identified as positively- and negatively-enriched, respectively, with gene set enrichment analysis. Gene sets representing specific liver metabolic pathways were associated with dysregulation of corresponding metabolites. Negative enrichment of liver adipogenesis and lipid metabolism corroborated with a significant reduction in most lipids in the serum samples of HCC patients. Two HCC subtypes from our Hispanic cohort were identified and validated with the TCGA liver cancer cohort. The subtype with better overall survival showed higher activity of immune and angiogenesis signatures, and lower activity of liver function-related gene signatures. It also had higher levels of immune checkpoint and immune exhaustion markers. Conclusions: Our study revealed some specific molecular features of Hispanic HCC and potential biomarkers for therapeutic management of HCC and provides a unique resource for studying Hispanic HCC.
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RATIONALE AND OBJECTIVES: Breast cancer mortality is 40% higher for Black women compared to White women. This study seeks to assess knowledge of breast cancer screening recommendations and identify barriers to risk assessment and mammographic screening among a medically underserved, low-income, predominantly Black community in West Philadelphia. MATERIALS AND METHODS: During a free mobile mammography screening event, women were offered surveys to assess perceptions of and barriers to breast cancer risk assessment and screening. Among those who subsequently underwent mobile screening, health insurance and time to additional diagnostic imaging and biopsy, when relevant, were retrospectively collected. RESULTS: 233 women completed surveys (mean age 54 ± 13 years). Ninety-three percent of respondents identified as Black. The most frequently cited barrier to screening mammography was cost and/or lack of insurance coverage (30%). Women under 50 reported more barriers to screening compared to older women. Among those recalled from screening and recommended to undergo biopsy, there was a trend toward longer delays between screening and biopsy among those without a PCP (median 45 days, IQR 25-53) compared to those with a PCP (median 24 days, IQR 16-29) (p = 0.072). CONCLUSION: In a study of a medically underserved community of primarily Black patients, barriers to breast cancer risk assessment, screening, and diagnosis were identified by self-report and by documented care delays. While free mobile mammography initiatives that bring medical professionals into communities can help mitigate barriers to screening, strategies for navigation and coordination of follow-up are critical to promote timely diagnostic resolution for all patients.