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Abstract: HOX transcript antisense intergenic RNA (HOTAIR) is one of the most studied long noncoding RNAs (lncRNAs) and is aberrantly expressed in colorectal cancer (CRC). We thus performed a comprehensive study based on meta-analysis and validation of the TCGA database to investigate clinicopathological and prognostic value of HOTAIR in CRC. Six studies enrolling 629 CRC patients were included in the analysis. The results indicated that high HOTAIR expression predicted worse OS (hazard ratio [HR] = 2.46, 95% confidence interval [CI]: 1.82-3.32, P < 0.01) and RFS (HR = 1.97, 95% CI: 1.27-3.05, P < 0.01) for CRC patients. High HOTAIR expression was also significantly associated with venous invasion (OR = 2.53, 95% CI: 1.12-5.68, P = 0.02), advanced tumor infiltration (OR = 3.35, 95% CI: 1.34-8.42, P = 0.01) and distant metastasis (OR = 5.52, 95% CI: 1.22-25.01, P = 0.03). Then, the results were validated by the TCGA database, showing that the up-regulated expression of HOTAIR was significantly related to poor OS (P = 0.01) and RFS (P = 0.04) in CRC. Our meta-analysis indicated that high HOTAIR expression was closely associated with poor clinical outcomes and could be a reliable prognostic biomarker for CRC patients.

Transcriptomic deregulation by epigenetic mechanisms plays a crucial role in the heterogeneous progression of colorectal cancer (CRC). Herein, we first demonstrated that the frequencies of the aberrancies of DNA methylation-correlated (METcor) and microRNA (miRNA)-correlated (MIRcor) genes were significantly co-regulated. Next, through integrative clustering of the expression profiles of METcor and MIRcor genes, four molecular subtypes were identified in CRC patients from The Cancer Genome Atlas and then validated in four independent datasets. More importantly, the four subtypes were well characterized and showed distinct clinical and molecular features: (i) S-I: high metabolic activity, sensitive to 5-fluorouracil-based chemotherapy and good prognosis; (ii) S-II: moderate metabolic activity, marked proliferation, frequent KRAS mutation and intermediate prognosis; (iii) S-III: moderate metabolic activity, marked proliferation, promoter DNA hypermethylation, high mutation burden, frequent BRAF and EGFR mutations, moderate levels of epithelial-mesenchymal transition (EMT) and transforming growth factor β (TGFβ) signals, immune-inflamed phenotype, sensitive to cetuximab and death protein-1 inhibitor treatment and relatively poor prognosis and (iv) S-IV: miRNA overexpression, stem/serrated/mesenchymal-like properties, hypoxia, high levels of EMT and TGFβ signals, immune-excluded phenotype and poor prognosis. Overall, this study established a molecular classification based on epigenetically regulated gene expression profiles, thereby providing a better understanding of the epigenetic mechanisms underlying CRC heterogeneity. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to assess the global burden of disease for developmental and intellectual disabilities caused by iodine deficiency from 1990 to 2019., Methods: Using data from the global burden of disease (GBD) 2019, we conducted a cross-country inequity analysis to examine the worldwide burden of developmental and intellectual disabilities caused by the issue of iodine deficiency from 1990 to 2019. Absolute and relative inequality were assessed by the slope index of inequality and the concentration index, respectively. After summarising the latest evidence, we also projected the age-standardized prevalence and years lived with disability (YLD) rates up to 2030 using the BAPC and INLA packages in R statistical software., Results: In 2019, the global age-standardized prevalence and YLD rates for developmental and intellectual disabilities due to iodine deficiency were 22.54 per 100,000 population (95% UI 14.47 to 29.23) and 4.12 per 100,000 population (95% UI 2.25 to 6.4), respectively. From 1990 to 2019, the age-standardized prevalence and YLD rates of developmental and intellectual disabilities due to iodine deficiency decreased significantly. Geographic distribution showed that areas with lower socio-demographic indices (SDI) were the most affected. The correlation between higher SDI and lower prevalence highlights the role of economic and social factors in the prevalence of the disease. Cross-national inequity analysis shows that disparities persist despite improvements in health inequalities. In addition, projections suggest that the disease burden may decline until 2030., Conclusion: This research underscores the necessity for targeted interventions, such as enhancing iodine supplementation and nutritional education, especially in areas with lower SDI. We aim to provide a foundation for policymakers further to research effective preventative and potential alternative treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Liu, Liu, He, Li, Li, Wu, Manyande, Feng and Xiang.)