The University of Hong Kong Gastric Cancer Organoids Genomics Study Data Access Committee
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ABSTRACT:
PROVIDER: EGAC00001000981 | EGA |
REPOSITORIES: EGA
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Project description:Objective: Cell-cell (CC) and cell-matrix (CM) adhesions are essential for epithelial cell survival, yet dissociation-induced apoptosis is frequently circumvented in malignant cells.
Design: We explored CC and CM dependence in 58 gastric cancer (GC) organoids by withdrawing either ROCK inhibitor, matrix, or both, to evaluate their tumorigenic potential in terms of apoptosis resistance, correlation with oncogenic driver mutations and clinical behaviour. We performed mechanistic studies to determine the role of diffuse-type GC drivers: ARHGAP fusions, RHOA, and CDH1, in modulating CC (CCi) or CM (CMi) adhesion independence.
Results: 97% of the tumour organoids were CMi, 66% were CCi and 52% were resistant to double withdrawal (CCi/CMi), while normal organoids were neither CMi nor CCi. Clinically, the CCi/CMi phenotype was associated with an infiltrative tumour edge and advanced tumour stage. Moreover, the CCi/CMi transcriptome signature was associated with poor patient survival when applied to 3 public GC datasets. CCi/CMi and CCi phenotypes were enriched in diffuse-type GC organoids, especially in those with oncogenic driver perturbation of RHO signalling via RHOA mutation or ARHGAP fusions. Inducible knockout of ARHGAP fusions in CCi/CMi tumour organoids led to re-sensitization to CC/CM dissociation-induced apoptosis, upregulation of focal adhesion and tight junction genes, partial reversion to a more normal cystic phenotype, and inhibited xenograft formation. Normal gastric organoids engineered with CDH1 or RHOA mutations became CMi or CCi, respectively.
Conclusions: The CCi/CMi phenotype has a critical role in malignant transformation and tumour progression, offering new mechanistic information on RHO-ROCK pathway inhibition that contributes to GC pathogenicity.
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Project description:Data Access Committee EGAC00001002705
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Project description:BackgroundWaterpipe smoking has gained global popularity in recent years, especially among young people. However, there is a lack of empirical investigation into waterpipe smoking in East Asia. This study aimed to investigate the demographical and psycho-social characteristics and patterns of waterpipe smoking (WPS) among university students in Hong Kong.MethodsA cross-sectional survey was conducted via online questionnaires administered to 1288 Hong Kong university students (mean age: 22.4 [SD = 3.8]). Logistic regressions were used to compute adjusted odd ratios (aOR) for waterpipe ever-smoking in relation to respondents' characteristics. Moreover, multinomial logistic regression yielded adjusted RR (aRR) for four different smoking status (i.e., never, waterpipe-only, cigarette-only, and dual smoking) regarding the characteristics.Results23.8% of participants reported having ever smoked a waterpipe (vs. cigarette ever-smoking: 21.1%). Factors including being female (aOR:1.57; 95% CI: 1.22-2.02), older age (≥24 years: 4.17; 1.35-12.93), frequent alcohol consumption (>monthly: 26.02; 10.91-62.09), and higher sensation-seeking behaviours (high level: 2.98;1.46-6.08) were associated with waterpipe ever-smokers. The study also identified that demographical and psycho-social characteristics were variably associated with students' smoking status. Particularly, more frequent alcohol consumption was most significantly associated with waterpipe-only smoking (aRR:45.73; 95% CI:11.44-182.73) (vs. cigarette-only smoking: 3.01; 1.76-5.14).ConclusionsWPS is the most common form of tobacco smoking among university students in Hong Kong, and characteristics unique to the population were identified. There is no legislation of relevant policies on WPS despite its concerning significance in public health among young people, therefore immediate action to monitor and control WPS is needed in Hong Kong.
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Project description:ImportanceCOVID-19 has required universities to rapidly develop vaccination policies for students and staff, yet little is known about the preferences of these individuals toward vaccination.ObjectiveTo quantify student and staff preferences for COVID-19 vaccination at a university in Hong Kong.Design, setting, and participantsA cross-sectional online survey study was conducted from July 20 to September 21, 2021, before the announcement of a campus-wide vaccine mandate. A survey of 42 451 eligible university students and staff used discrete-choice experiment methods to quantify 7 attributes of COVID-19 vaccination: risk of a mild or moderate adverse event after vaccination, risk of a severe adverse event after vaccination, efficacy against COVID-19 infection, efficacy against severe manifestation of COVID-19 infection, duration of protection after vaccination, incentive for completing vaccination, and out-of-pocket costs.Main outcomes and measuresA mixed logit regression model was used to estimate the preferences of attributes for COVID-19 vaccines and marginal willingness to pay (mWTP) adjusted for background characteristics, role, vaccination, and COVID-19 infection status of family or friends, adverse event status after vaccination among family and friends of participants, and scenario block.ResultsAmong 42 451 eligible university students and staff invited, 3423 individuals completed the survey (mean [SD] age, 27.1 [9.9] years; 2053 [60.0%] women). Participants included 2506 students (73.2%) and 917 staff (26.8%), with a response rate of 8.1%. Quarantine-free travel was preferred (β = 0.86; 95% CI, 0.72-0.99; mWTP: $235.9; 95% CI, $190.3-$294.2), followed by efficacy against any COVID-19 infection (β = 0.30; 95% CI, 0.29-0.32; mWTP: $84.1; 95% CI, $71.8-$100.8), against severe manifestation of COVID-19 infection (β = 0.25; 95% CI, 0.24-0.27; mWTP: $69.7; 95% CI, $465-$653), and risk of severe adverse events following vaccination (β = -0.24; 95% CI, -0.27 to -0.21; mWTP: -$66.8; 95% CI, -$81.5 to -$55.3). Participants were less concerned about protection duration (β = 0.17; 95% CI, 0.15-0.18; mWTP: $46.0; 95% CI, $38.6-$56.2) and risk of mild to moderate adverse events (β = -0.12; 95% CI, -0.13 to -0.10; mWTP: -$32.7; 95% CI, -$41.2 to -$26.4).Conclusions and relevancePreference of all attributes were significant and were considered important by the participants for vaccine decision-making. Insights drawn could assist policy makers in future vaccination decisions, such as campus vaccine mandate and requirement of a third dose.
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