CTC together with Shh and Nrf2 are prospective diagnostic markers for HNSCC.

BACKGROUND: The lack of appropriate prognostic biomarkers remains a significant obstacle in the early detection of Head and Neck Squamous Cell Carcinoma (HNSCC), a cancer type with a high mortality rate. Despite considerable advancements in treatment, the success in diagnosing HNSCC at an early stage still needs to be improved. Nuclear factor erythroid 2-related factor 2 (Nrf2) and Sonic Hedgehog (Shh) are overexpressed in various cancers, including HNSCC, and have recently been proposed as possible therapeutic targets for HNSCC. Circulating Tumor Cell (CTC) is a novel concept used for the early detection of cancers, and studies have suggested that a higher CTC count is associated with the aggressiveness of HNSCC and poor survival rates. Therefore, we aimed to establish molecular markers for the early diagnosis of HNSCC considering Shh/Nrf2 overexpression in the background. In addition, the relation between Shh/Nrf2 and CTCs is still unexplored in HNSCC patients. METHODS: In the present study, we selected a cohort of 151 HNSCC patients and categorized them as CTC positive or negative based on the presence or absence of CTCs in their peripheral blood. Data on demographic and clinicopathological features with the survival of the patients were analyzed to select the patient cohort to study Shh/Nrf2 expression. Shh and Nrf2 expression was measured by qRT-PCR. RESULTS: Considering significant demographic [smoking, betel leaf (p-value < 0.0001)] and clinicopathological risk factors [RBC count (p < 0.05), Platelet count (p < 0.05), Neutrophil count (p < 0.005), MCV (p < 0.0001), NLR (p < 0.05), MLR (p < 0.05)], patients who tested positive for CTC also exhibited significant overexpression of Shh/Nrf2 in both blood and tissue compared to CTC-negative patients. A strong association exists between CTCs and tumor grade. Following chemotherapy (a combination of Cisplatin, 5FU, and Paclitaxel), the frequency of CTCs was significantly decreased in patients with HNSCC who had tested positive for CTCs. The Kaplan-Meier plot illustrated that a higher number of CTCs is associated with poorer overall survival (OS) in patients with HNSCC. CONCLUSIONS: Detecting CTCs, and higher expression of Shh and Nrf2 in HNSCC patients' blood, can be a promising tool for diagnosing and prognosticating HNSCC.

Reduced IFN-γ levels along with changes in hematologic and immunologic parameters are key to COVID-19 severity in Bangladeshi patients.

The manifestation of coronavirus disease 2019 (COVID-19) severity and mortality has been associated with dysregulation of the immune response, often influenced by racial disparities and conferred by changes in hematologic and immunologic parameters. These biological and hematologic parameters as well as cytokine profiles were investigated in a cohort of 61 COVID-19-positive patients (categorized into mild, moderate, and severe groups) from Bangladesh using standard analytical methods. The data reported that the interleukin (IL)-4 and IL-6 levels were significantly increased, whereas the levels of interferon (IFN)-γ were significantly reduced in patients with severe COVID-19 (p < 0.05) compared with those in patients with mild and/or moderate COVID-19. The extent of erythrocyte sedimentation rate (ESR); neutrophil count; and levels of ferritin, C-reactive protein (CRP), and D-dimer (p < 0.05) were found to be significantly increased, whereas the white blood cell (WBC), lymphocyte, eosinophil, and platelet counts (p < 0.05) were observed to be significantly reduced in patients with severe COVID-19 compared with those in the patients in other 2 groups. Our study exhibited a significantly higher IL-6-to-lymphocyte ratio in patients with severe COVID-19 than in those with mild and moderate COVID-19. The calculated neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and ferritin-to-ESR ratio were significantly increased in patients with severe COVID-19. The increase in the IL-4 and IL-6 levels along with CRP and D-dimer levels may envisage a hyperinflammatory environment and immune dysregulation, which contribute to prolonged viral persistence, leading to severe disease. However, the reduced level of IFN-γ can be attributed to a less fatality toll in Bangladesh compared with that in the rest of the world.