Yi Jiang

The global, regional and national burden of three female pelvic cancers attributable to high BMI from 1990 to 2021: a systematic analysis for the Global Burden of Disease Study 2021 and projection to 2050

Abstract High BMI is an important risk factor for female colon and rectal, ovarian and uterine cancers. Current comprehensive studies on its effects on these cancers are limited. This paper aims to explore regional and age differences in the impact of high BMI on these cancers and the commonalities among the three by using the Global Burden of Disease 2021. Deaths, disability-adjusted life years and their age-standardised rates for these cancers were retrieved from 1990 to 2021, and burden trends were assessed using the estimated annual percentage change and percentage changes. The study also analysed the correlation between age-standardised rate and socio-demographic index across twenty-one regions and projected future disease burden trends using the Bayesian Age-Period-Cohort model. Results showed that the global burden of female colon and rectal cancer declined since 1990 but remained at the highest level among the three cancers in 2021. At the same time, these three cancers had high burdens in high-income areas. Since 1990, ovarian and uterine cancer burdens attributable to high BMI increased, and all three burdens grew fastest in low-middle-income regions and among younger people. The burden of all three is projected to continue increasing through 2050. This study confirms that high BMI’s impact on these cancers is regional and age-specific, with long-term effects. Therefore, subsequent public health interventions should adopt more targeted obesity prevention and control strategies based on national and regional situations to effectively mitigate the adverse effects of high BMI on these cancers.

YBX1 promotes homologous recombination and resistance to platinum-induced stress in ovarian cancer by recognizing m5C modification

Platinum-based chemotherapy causes genetic damage and induces apoptosis in ovarian cancer cells. Enhancing the ability to resist platinum drug-induced DNA damage and apoptotic stress is critical for tumor cells to acquire drug resistance. Here, we found that Y-box binding protein 1 (YBX1) was highly expressed in cisplatin-resistant patient-derived organoids (PDOs) and was a crucial gene for alleviating platinum-induced stress and maintaining drug resistance characteristics in ovarian cancer cells. Mechanistically, YBX1 recognized m5C modifications in CHD3 mRNA and maintained mRNA stability by recruiting PABPC1 protein. This regulatory process enhanced chromatin accessibility and improved the efficiency of homologous recombination (HR) repair, facilitating tumor cells to withstand platinum-induced apoptotic stress. In addition, SU056, an inhibitor of YBX1, exhibited the potential to reverse platinum resistance in subcutaneous and PDO orthotopic xenograft models. In conclusion, YBX1 is critical for ovarian cancer cells to alleviate the platinum-induced stress and may be a potential target for reversing drug-resistant therapies.