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Abstract Cell annotation is a crucial methodological component to interpreting single cell and spatial omics data. These approaches were developed for single cell analysis but are often biased, manually curated and yet unproven in spatial omics. Here we apply a stemness model for assessing oncogenic states to single cell and spatial omic cancer datasets. This one-class logistic regression machine learning algorithm is used to extract transcriptomic features from non-transformed stem cells to identify dedifferentiated cell states in tumors. We found this method identifies single cell states in metastatic tumor cell populations without the requirement of cell annotation. This machine learning model identified stem-like cell populations not identified in single cell or spatial transcriptomic analysis using existing methods. For the first time, we demonstrate the application of a ML tool across five emerging spatial transcriptomic and proteomic technologies to identify oncogenic stem-like cell types in the tumor microenvironment.

Endometrial cancer is the most common gynecologic cancer in the United States. Over the last several decades, the incidence of aggressive tumors, and thus the rate of death from disease, has increased significantly. The population most affected by these epidemiologic shifts are Black women. Symptom awareness, lack of treatment access, and failure of providers to provide guideline-concordant care are just some of the drivers behind these changes. Race as a social construct has historically categorized women into groups that are not reflective of the nuanced personalization that is required for cancer prevention strategies and targeted cancer treatments. There is, however, an increasing understanding that disaggregation by place of birth and social context are important to understand care-seeking behaviors, genetic drivers of disease, and factors that lead to deleterious outcomes. In this review, we will focus on specific individual-level influences that impact disease diagnosis and care-seeking among Black women, recognizing that the global disparities which exist in this disease encompass multiple domains. Such considerations are crucial to understanding drivers of self-efficacy and to develop programs for knowledge awareness and empowerment within a framework that is both useful and acceptable to these diverse communities at risk.

Abstract Lynch Syndrome (LS) prevalence in underrepresented minorities are lacking. The objective of this study was to assess the prevalence of LS in a minority patient population. Secondary objectives included identifying factors associated with successful LS screening and to characterize clinicopathologic features. Women with endometrial cancer treated within a university system from 2014 and 2016 were included. Immunohistochemistry (IHC) results of MLH1, PMS2, MSH2 and MSH6 were obtained from medical records and clinicopathologic factors abstracted. Patients not previously screened for LS were screened. 276 patients were evaluable. More minority women were screened as part of their routine cancer care (p = 0.005). Additionally, women 50 years or younger were more likely to be screened for LS compared to women older than 51(p = 0.009) and uninsured or reliant on Medicaid patients (p = 0.011) were more likely to be screened during routine care. Six patients received confirmatory germline testing for LS (4.3%), and another 8 patients had a staining pattern suggestive of LS. In an underrepresented population, the rate of LS in endometrial cancer is similar to previous reports. LS may be under diagnosed and opportunities missed when universal screening is not applied in minority women.

PURPOSEUnderstanding the distribution of human papilloma virus (HPV) subtypes in limited-resource settings is imperative for cancer prevention strategies in these regions. The objective of our study is to compare the prevalence of cervical HPV genotypes in women across the African diaspora.METHODSThis study was approved by the African Caribbean Consortium (AC3). Six member institutions (Benin, Ethiopia, The Bahamas, Tobago, Curacao, and Jamaica) provided independently collected HPV data. Prevalence comparisons across for each nation were performed followed by an assessment of anticipated 9-valent vaccine coverage. Chi-square or Fisher's exact tests were used with significance at P < .05.RESULTSOne thousand three hundred fifty high-risk (HR) and 584 low-risk (LR) HPV subtypes were identified in the entire cohort. The most common HR HPV subtype was HPV 16 (17.9%) of infections. The distribution of HR and LR subtypes varied by country. The proportion of HR-HPV subtypes covered by the current 9-valent vaccine was lower in African countries compared with the Caribbean countries (47.9% v 67.9%; P < .01). No significant difference was seen for LR subtypes (8.1% African continent v 5.2% Caribbean; P = .20). Marked variation in the proportion of infections covered by the 9-valent vaccine persisted in individual countries.CONCLUSIONSignificant variations in HPV prevalence were identified among African and Afro-Caribbean women. A large number of women in these regions are potentially uncovered by current vaccination formulation, particularly low-risk HPV infections.

Racist and discriminatory federal, state, and local housing policies significantly contribute to disparities in cardiovascular disease incidence and mortality for individuals that self-identify as Black or African American. Here we highlight three key housing policies – “redlining,” zoning, and the construction of highways – which have wrought a powerful, sustained, and destructive impact on cardiovascular health in Black/African American communities. Redlining and highway construction policies have restricted access to quality health care, increased exposure to carcinogens such as PM2.5, and increased exposure to extreme heat. At the root of these policy decisions are longstanding, toxic societal factors including racism, segregation, and discrimination, which also serve to perpetuate racial inequities in cardiovascular health. Here, we review these societal and structural factors and then link them with biological processes such as telomere shortening, allostatic load, oxidative stress, and tissue inflammation. Lastly, we focus on the impact of inflammation on the immune system and the molecular mechanisms by which the inflamed immune microenvironment promotes the formation of atherosclerotic plaques. We propose that racial residential segregation and discrimination increases tissue inflammation and cytokine production, resulting in dysregulated immune signaling, which promotes plaque formation and cardiovascular disease. This framework has the power to link structural racism not only to cardiovascular disease, but also to cancer.

Background: Estrogen receptor positive (ER+) breast cancer is one of the most commonly diagnosed malignancies in women irrespective of their race or ethnicity. While Black women with ER+ breast cancer are 42% more likely to die of their disease than White women, molecular mechanisms underlying this disparate outcome are understudied. Recent studies identify DNA damage repair (DDR) genes as a new class of endocrine therapy resistance driver that contributes to poor survival among ER+ breast cancer patients. Here, we systematically analyze DDR regulation in the tumors and normal breast of Black women and its impact on survival outcome. Method: Mutation and up/downregulation of 104 DDR genes in breast tumor and normal samples from Black patients relative to White counterparts was assessed. For DDR genes that were differently regulated in the tumor samples from Black women in multiple datasets associations with survival outcome were tested. Results: Overall, Black patient tumors upregulate or downregulate RNA levels of a wide array of single strand break repair (SSBR) genes relative to their white counterparts and uniformly upregulate double strand break repair (DSBR) genes. This DSBR upregulation was also detectable in samples of normal breast tissue from Black women. Eight candidate DDR genes were reproducibly differently regulated in tumors from Black women and associated with poor survival. A unique DDR signature comprised of simultaneous upregulation of homologous recombination gene expression and downregulation of SSBR genes was enriched in Black patients. This signature associated with cell cycle dysregulation ( p

Background: Caribbean immigrants represent one of the largest groups of minorities in the United States (US), yet are understudied. Racial and ethnic disparities among women with ovarian cancer have been reported, but not in immigrant populations. Our objective was to evaluate differences in the clinicopathologic features and survival outcomes of Caribbean-born (CB) immigrants with ovarian cancer, with special focus on the influence of race and ethnicity on these measures.Methods: A review of the institutional cancer registry was performed to identify women with known nativity treated for epithelial ovarian cancer between 2005 and 2017. Sociodemographic, clinical, and outcomes data were collected. Analyses were done using chi-square, Cox proportional hazards models, and the Kaplan-Meier method, with significance set at p < 0.05.Results: 529 women were included in the analysis, 248 CB and 281 US-born (USB). CB women were more likely to have residual disease after debulking surgery (31.2 vs. 16.8%, p = 0.009) and be treated at a public facility (62.5 vs. 33.5%, p < 0.001). Black CB women less frequently received chemotherapy compared to White CB women (55.2 vs. 82.2%, p = 0.001). Among all CB women, Hispanic ethnicity was independently associated with improved survival when adjusting for other factors (HR 0.61 [95% CI 0.39–0.95], p = 0.03). White Hispanic CB women had a median overall survival (OS) of 59 months while Black, non-Hispanic CB women had a median OS of 24 months (log-rank p = 0.04).Conclusion: Among Caribbean-born women with ovarian cancer, Hispanic ethnicity is significantly associated with improved survival outcomes, regardless of race.

Besides BRCA1 and BRCA2, several other inheritable mutations have been identified that increase ovarian cancer risk. Surgical excision of the fallopian tubes and ovaries reduces ovarian cancer risk, but for some non-BRCA hereditary ovarian cancer mutations the benefit of this intervention is unclear. The fallopian tubes of women with hereditary ovarian cancer mutations provide many insights into the early events of carcinogenesis and process of malignant transformation. Here we review cancer pathogenesis in hereditary cases of ovarian cancer, the occurrence of pre-invasive lesions and occult carcinoma in mutation carriers and their clinical management.