The prevalence of high-risk human papillomavirus (HPV) DNA in cases of oral cavity squamous cell carcinoma (SCC) varies widely. The aim of this study is to investigate the frequency of high-risk HPV DNA in a large Brazilian cohort of patients with oral cavity SCC. Biopsy and resected frozen and formalin-fixed paraffin-embedded specimens of oral cavity SCC were available from 101 patients who were recruited at two Brazilian centres. Stringent measures with respect to case selection and prevention of sample contamination were adopted to ensure reliability of the data. Nested PCR using MY09/MY11 and GP5⁺/GP6⁺ as well as PGMY09/11 L1 consensus primers were performed to investigate the presence of HPV DNA in the tumours. HPV-positive cases were subjected to direct sequencing. Shapiro–Wilk and Student t test were used to evaluate data normality and to compare the means, respectively. Qualitative variables were analysed by logistic regression. Our results demonstrate that the frequency of high-risk HPV types in oral cavity SCC is very low and is less than 4%. All HPV-positive cases were HPV16. In addition, our results do not show a significant association between the tumour clinical features and the risk factors (tobacco, alcohol and HPV) for oral cavity SCC. In the current study, we observed an overlapping pattern of risk factors that are related to tumour development. This, along with a low frequency of high-risk HPV DNA, supports the findings that HPV is not involved in the genesis of oral cavity SCC in Brazilian population.

Pedro L. Azevedo, Rhayra B. Dias, Liebert P. Nogueira, Simone Maradei, Ricardo Bigni, Jordana S. R. Aragao, Eliana Abdelhay, Renata Binato. IJSC 2022;15:227-32. https://doi.org/10.15283/ijsc21138

Acute myeloid leukaemia (AML) is a severe haematological neoplasm that originates from the transformation of haematopoietic stem cells (HSCs) into leukaemic stem cells (LSCs). The bone marrow (BM) microenvironment, particularly that of mesenchymal stromal cells (hMSCs), plays a crucial role in the maintenance of HSCs. In this context, we explored whether alterations in the secretome of hMSCs derived from AML patients (hMSC-AML) could impact HSC gene expression. Proteomic analysis revealed that the secretome of coculture assays with hMSC-AMLs and HSC from healthy donor is altered, with increased levels of secretory leukocyte protease inhibitor (SLPI), a protein associated with important processes for maintenance of the haematopoietic niche that has already been described to be altered in several tumours. Increased SLPI expression was also observed in the BM plasma of AML patients. Transcriptome analysis of HSCs cocultured with hMSC-AML in comparison with HSCs cocultured with hMSC-HD revealed altered expression of SLPI target genes associated with the cell cycle, proliferation, and apoptosis. Important changes were identified, such as increased expression levels of CCNA2, CCNE2, CCND2, CD133 and CDK1 and decreased levels of CDKN2A and IGFBP3, among others. Overall, these findings suggest that the altered secretome of coculture assays with hMSC-AMLs and HSC from healthy donor, particularly increased SLPI expression, can contribute to gene expression changes in HSCs, potentially influencing important molecular mechanisms related to AML development and progression.

Background/Objectives: Despite its heterogeneity and diagnostic challenges, acute myeloid leukemia (AML) originates from stem cell transformation and alterations in the hematopoietic niche (HN) could be related to leukemic transformation. Therefore, the aim of this study was to evaluate the protein profile of HN from AML patients and compare it with the profile of healthy donors (HDs). Methods: A proteomic analysis was conducted to identify differentially expressed (DE) proteins in BM plasma from AML patients and HD. In silico analysis was performed to identify biological processes and signaling pathways involved. Additionally, ELISA confirmed the expression of the DE protein of interest in BM plasma samples. Results: Proteomic analysis revealed alterations in the plasma profiles of AML patients and 36 DE proteins were found. Among then, we highlight C8G, CFB, SAA1, SERPINA3 and SERPINC1, which are related to inflammatory response process. Thus, considering the role of the secreted protein SAA1 in the inflammatory context and that it is described as a potential biomarker in several tumors, we selected SAA1 for ELISA confirmation. The results corroborated our findings, indicating that increased expression of SAA1 could be related to AML. Our results also revealed that SAA1 can stimulate immune signaling through NF-kappa-B activation. Conclusions: These findings position SAA1 as a promising biomarker for AML diagnosis, offering a potential tool for more accurate identification of the disease. Nevertheless, further studies are needed to understand the relationship of SAA1 with the leukemic transformation process in AML and its potential clinical use.