Mortality-to-incidence ratio of early-onset colorectal cancer in high-income Asian and Middle Eastern countries: A systemic analysis of the Global Burden of Diseases Study 2019.

BACKGROUND: The incidence of early-onset colorectal cancer (EO-CRC) has been consistently rising leading to a significant cancer burden among younger adults in Asian and Middle Eastern high-income countries. The study aims to investigate the survival outcomes of EO-CRC among high-income Asian and Middle Eastern populations from 1990 to 2019 using the mortality-to-incidence ratio, with a focus on examining the differences in gender. METHODS: This is a systematic analysis of the Global Burden of Disease (GBD) 2019 study. We include individuals aged 15 to 49 years old in high-income Asian and the Middle Eastern countries. The colorectal cancer mortality-to-incidence ratio (MIR) was calculated for both genders by dividing the age-specific mortality rate per 100,000 for colorectal cancer by the age-specific incidence rate per 100,000 for each nation in the sample for a given year. RESULTS: An overall decline in male and female MIR was observed from 1990 to 2019 in Asian and Middle Eastern countries. Ten out of thirteen Asian and Middle Eastern countries had a higher female MIR compared to their male counterparts. The global male MIR was found to be significantly higher than that of female (p-value 0.008, coefficient estimate: 1.51). In Middle Eastern countries, Saudi Arabia had a significantly higher female MIR compared to their male counterparts (p < 0.0001, coefficient estimate: 12.65). CONCLUSION: This research addresses the knowledge gap concerning gender-based differences in EO-CRC survival outcomes in high-income Asian and Middle Eastern countries, providing insights into the factors influencing these disparities in these regions. Policymakers should focus on developing targeted prevention and treatment programs for women, and addressing cultural and social barriers that may prevent women from seeking timely medical care.

Using NMR spectroscopy to investigate the role played by copper in prion diseases.

Prion diseases are a group of rare neurodegenerative disorders that develop as a result of the conformational conversion of normal prion protein (PrPC) to the disease-associated isoform (PrPSc). The mechanism that actually causes disease remains unclear. However, the mechanism underlying the conformational transformation of prion protein is partially understood-in particular, there is strong evidence that copper ions play a significant functional role in prion proteins and in their conformational conversion. Various models of the interaction of copper ions with prion proteins have been proposed for the Cu (II)-binding, cell-surface glycoprotein known as prion protein (PrP). Changes in the concentration of copper ions in the brain have been associated with prion diseases and there is strong evidence that copper plays a significant functional role in the conformational conversion of PrP. Nevertheless, because copper ions have been shown to have both a positive and negative effect on prion disease onset, the role played by Cu (II) ions in these diseases remains a topic of debate. Because of the unique properties of paramagnetic Cu (II) ions in the magnetic field, their interactions with PrP can be tracked even at single atom resolution using nuclear magnetic resonance (NMR) spectroscopy. Various NMR approaches have been utilized to study the kinetic, thermodynamic, and structural properties of Cu (II)-PrP interactions. Here, we highlight the different models of copper interactions with PrP with particular focus on studies that use NMR spectroscopy to investigate the role played by copper ions in prion diseases.

Molecular characterisation in tongue squamous cell carcinoma reveals key variants potentially linked to clinical outcomes.

BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) is a highly aggressive malignancy characterized by frequent recurrence, poor survival with relatively few therapeutic options due to the late diagnosis in many cases. OBJECTIVES: Understanding the molecular pathways underlying OTSCC tumourigenesis and the discovery of diagnostic and/or prognostic biomarkers. METHODS: We performed high-throughput mutational analysis of 44 OTSCC formalin-fixed paraffin-embedded (FFPE) cases using the Cancer Hotspots Panel (CHP) v2 on the Ion Torrent™platform. We determined the frequency of human papilloma virus (HPV) using PCR and Epstein bar virus (EBV) positivity using immunohistochemistry. As a control for EBV infection we screened matched non-tumourous tissues. RESULTS: Sequencing analysis identified missense, nonsense and frameshift mutations in TP53 (66%), PIK3CA (27%), CDKN2A (25%), EGFR (18%), and PTEN (14%). Interestingly, no significant associations were found between damaging mutations and clinicopathological data. A total of 10/44 of the OTSCC samples (23%) tested was positive for HPV18 DNA. OTSCC patients with positive HPV infection had worse overall survival compared to HPV-negative cases as determined by Kaplan-Meier survival (p= 0.023). Furthermore, EBNA1 expression showed a strong tumour-enriched expression pattern in 20 out of 21 samples (95%) in the epithelial compartments of the tissues analysed. CONCLUSIONS: Taken together, this study highlights that the two most common events in OTSCC are TP53 mutations and EBV positivity. Helping to understand the contribution of TP53 mutations and EBV infection events could serve as useful biomarkers for OTSCC.

Prognostic potential of KLOTHO and SFRP1 promoter methylation in head and neck squamous cell carcinoma.

Hypermethylation in the CpG island promoter regions of tumor suppressors is known to play a significant role in the development of HNSCC and the detection of which can aid the classification and prognosis of HNSCC. This study aims to profile the methylation patterns in a panel of key genes including CDKN2A, CDKN2B, KLOTHO (KL), RASSF1A, RARB, SLIT2, and SFRP1, in a group of HNSCC samples from Saudi Arabia. The extent of methylation in these genes is determined using the MethyLight assay and correlated with known clinicopathological parameters in our samples of 156 formalin-fixed and paraffin-embedded HNSCC tissues. SLIT2 methylation had the highest frequency (64.6%), followed by RASSF1A (41.3%), RARB (40.7%), SFRP1 (34.9), KL (30.7%), CKDN2B (29.6%), and CKDN2A (29.1%). KL and SFRP1 methylation were more predominant in nasopharyngeal tumors (P = 0.001 and P = 0.031 respectively). Kaplan Meier analysis showed that patients with moderately differentiated tumors who display SFRP1 methylation have significantly worse overall survival in comparison with other samples. In contrast, better clinical outcomes were seen in patients with KL methylation. In conclusion, our findings suggest that the detection of frequent methylation in SFRP1 and KL genes' promoters could serve as prognostic biomarkers for HNSCC.