RESUMEN
Peripheral blood transcriptomes from 383 patients with newly diagnosed melanoma were subjected to differential gene expression analysis. The hypotheses were that impaired systemic immunity is associated with poorer prognosis (thicker tumors and fewer tumor-infiltrating lymphocytes) and evidence of systemic inflammation (high-sensitivity CRP and fibrinogen levels). Higher fibrinogen levels were associated with thicker primary tumors. In single-gene analysis, high-sensitivity CRP levels were significantly associated with higher blood CD274 expression (coding for PD-L1), but each was independently prognostic, with high-sensitivity CRP associated with increased mortality and higher CD274 protective, independent of age. Pathway analysis identified downregulation of immune cell signaling pathways in the blood of people with thicker tumors and notable upregulation of signal transducer and activator of transcription 1 gene STAT1 in people with brisk tumor-infiltrating lymphocytes. Transcriptomic data provided evidence for increased NF-kB signaling with higher inflammatory markers but with reduction in expression of HLA class II molecules and higher CD274, suggesting that aberrant systemic inflammation is a significant mediator of reduced immune function in melanoma. In summary, transcriptomic data revealed evidence of reduced immune function in patients with thicker tumors and fewer tumor-infiltrating lymphocytes at diagnosis. Inflammatory markers were associated with thicker primaries and independently with death from melanoma, suggesting that systemic inflammation contributes to that reduced immune function.
RESUMEN
Background: There is a known lack of diversity in research participant populations. This impacts on the generalisability of findings and affects clinician prescribing. In the United Kingdom the research community defines those who are underrepresented as under-served. They are commonly those affected by health inequality and disparity. The notion of under-served is complex, with numerous papers identifying multiple factors that contribute to being under-served and in turn suggesting many strategies to improve engagement. Methods: Research professionals in the UK were invited to complete an online survey. The broad aim was to explore their views on under-served groups. The findings were analysed using statistical and qualitative methods to identify enablers and barriers to engaging the under-served. Descriptive statistics were utilised with associations compared univariately by chi-square test and logistic regression for multivariable analysis. Results: A total of 945 completed responses were received. Those identified as under-served in this study reflected the previous body of works with a broader descriptor of ethnic and cultural minorities and the addition of adolescents and young adults. Language and literacy skills had the most impact on being under-served. Only 13% of respondents said they felt equipped to meet the needs of the under-served. The main strategy to increase diversity was community engagement and movement of research delivery into the community. The barriers were funding and time. Training needs identified were linked to community engagement, cultural competence and consent processes. Conclusions: The UK findings from research professionals reflected the previous literature. Adolescents and young people were added to those identified as under-served. Enablers included community outreach and improvement to communication. Barriers were time, funding, organisational processes and lack of focus. Issues were identified with translation and interpretation services. Training requirements focus on methodologies and methods to engage and the consent processes of those from under-served groups.
Research study participants do not reflect the general population. This means that findings from research cannot be reliably transferred to the general population. The people missing are termed under-served or underrepresented. These people come from groups who have unequal access to health care and have poorer health. There are different reasons why people may not take part in research and many ways to support them to take part. This project asked the people who work in research who they thought were missing from research studies. It asked, what would make it easier for people to take part and what got in the way. Those who work in research were invited to write their thoughts in an online survey. Answers were then looked at using tests to find out the number of people who said the same or different things. Other answers were looked at to find out their views and opinions. A total of 945 people filled in the questionnaire. Those who responded thought the biggest group of people who were missing from research populations were from minority social and cultural groups. They also thought teenagers and young adults were missing from research. When asked why people didn't take part the biggest problem was with making research easy to understand. Only 13% of the people who filled in the survey thought they were able to help those who were missing. It was suggested the best way to improve the number of different people taking part in research was to move research from hospitals to the places where the under-served live. The biggest thing that stopped those working in research helping was funding and time. They also wanted to find out how to carry out research in the community, how to help different cultural groups and aid those with certain medical conditions.