SummaryBackgroundGlobal inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia.MethodsCancer registries participating in CONCORD were asked to submit tumour registrations for all children aged 0–14 years who were diagnosed with leukaemia between Jan 1, 1995, and Dec 31, 2009, and followed up until Dec 31, 2009. Haematological malignancies were defined by morphology codes in the International Classification of Diseases for Oncology, third revision. We excluded data from registries from which the data were judged to be less reliable, or included only lymphomas, and data from countries in which data for fewer than ten children were available for analysis. We also excluded records because of a missing date of birth, diagnosis, or last known vital status. We estimated 5-year net survival (ie, the probability of surviving at least 5 years after diagnosis, after controlling for deaths from other causes [background mortality]) for children by calendar period of diagnosis (1995–99, 2000–04, and 2005–09), sex, and age at diagnosis (<1, 1–4, 5–9, and 10–14 years, inclusive) using appropriate life tables. We estimated age-standardised net survival for international comparison of survival trends for precursor-cell acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML).FindingsWe analysed data from 89 828 children from 198 registries in 53 countries. During 1995–99, 5-year age-standardised net survival for all lymphoid leukaemias combined ranged from 10·6% (95% CI 3·1–18·2) in the Chinese registries to 86·8% (81·6–92·0) in Austria. International differences in 5-year survival for childhood leukaemia were still large as recently as 2005–09, when age-standardised survival for lymphoid leukaemias ranged from 52·4% (95% CI 42·8–61·9) in Cali, Colombia, to 91·6% (89·5–93·6) in the German registries, and for AML ranged from 33·3% (18·9–47·7) in Bulgaria to 78·2% (72·0–84·3) in German registries. Survival from precursor-cell ALL was very close to that of all lymphoid leukaemias combined, with similar variation. In most countries, survival from AML improved more than survival from ALL between 2000–04 and 2005–09. Survival for each type of leukaemia varied markedly with age: survival was highest for children aged 1–4 and 5–9 years, and lowest for infants (younger than 1 year). There was no systematic difference in survival between boys and girls.InterpretationGlobal inequalities in survival from childhood leukaemia have narrowed with time but remain very wide for both ALL and AML. These results provide useful information for health policy makers on the effectiveness of health-care systems and for cancer policy makers to reduce inequalities in childhood cancer survival.FundingCanadian Partnership Against Cancer, Cancer Focus Northern Ireland, Cancer In...

Hepatocellular carcinoma (HCC) is one of the most malignant human tumours because of its high incidence of metastasis. The mechanisms underlying the metastasis of HCC, however, remain poorly understood. In this study, we performed cDNA microarray analysis to profile gene expression patterns in two subtypes of HCC, solitary large HCC (SLHCC) and nodular HCC (NHCC), which differ significantly in the incidence of metastasis. Among 668 genes that were differentially expressed, we focused on RhoC, whose expression was significantly decreased in SLHCC compared to NHCC. The expression of RhoC in HCC and pericarcinomatous liver tissues (PCLT) was analysed at both the mRNA and protein levels by reverse transcription -polymerase chain reaction (RT -PCR) and Western blotting. In addition, immunohistochemistry was also performed on 94 cases of HCC with follow-up information. Collectively, our data indicate that the expression of RhoC significantly increased in HCC compared to PCLT; extrahepatic metastatic lesions expressed significantly higher levels of RhoC than the corresponding intrahepatic HCC tissues. There is a highly significant correlation of the RhoC expression levels with tumour vein invasion, number of tumour nodes and the status of differentiation. Significantly, the HCC patients with RhoC-positive expression had shorter survival than those with RhoC-negative expression. Together, our findings suggest a strong correlation between the expression of RhoC and HCC metastasis, implicating RhoC as a potential prognosis marker and therapeutic target for HCC.

Coronavirus disease 2019 (COVID-19) was first detected in December 2019 in Wuhan, China, with 11,669,259 positive cases and 539,906 deaths globally as of July 8, 2020. The objective of the present study was to determine whether meteorological parameters and air quality affect the transmission of COVID-19, analogous to SARS. We captured data from 29 provinces, including numbers of COVID-19 cases, meteorological parameters, air quality and population flow data, between Jan 21, 2020 and Apr 3, 2020. To evaluate the transmissibility of COVID-19, the basic reproductive ratio ( R 0 ) was calculated with the maximum likelihood “removal” method, which is based on chain-binomial model, and the association between COVID-19 and air pollutants or meteorological parameters was estimated by correlation analyses. The mean estimated value of R 0 was 1.79 ± 0.31 in 29 provinces, ranging from 1.08 to 2.45. The correlation between R 0 and the mean relative humidity was positive, with coefficient of 0.370. In provinces with high flow, indicators such as carbon monoxide (CO) and 24-h average concentration of carbon monoxide (CO_24 h) were positively correlated with R 0 , while nitrogen dioxide (NO 2 ), 24-h average concentration of nitrogen dioxide (NO 2 _24 h) and daily maximum temperature were inversely correlated to R 0 , with coefficients of 0.644, 0.661, −0.636, −0.657, −0.645, respectively. In provinces with medium flow, only the weather factors were correlated with R 0 , including mean/maximum/minimum air pressure and mean wind speed, with coefficients of −0.697, −0.697, −0.697 and −0.841, respectively. There was no correlation with R 0 and meteorological parameters or air pollutants in provinces with low flow. Our findings suggest that higher ambient CO concentration is a risk factor for increased transmissibility of the novel coronavirus, while higher temperature and air pressure, and efficient ventilation reduce its transmissibility. The effect of meteorological parameters and air pollutants varies in different regions, and requires that these issues be considered in future modeling disease transmissibility.

The tumor microenvironment (TME) has a strong influence on the progression, therapeutic response, and clinical outcome of acute myeloid leukemia (AML), one of the most common hematopoietic malignancies in adults. In this study, we identified TME-related genes associated with AML prognosis. Gene expression profiles from AML patients were downloaded from TCGA database, and immune and stromal scores were calculated using the ESTIMATE algorithm. Immune scores were correlated with clinical features such as FAB subtypes and patient’s age. After categorizing AML cases into high and low score groups, an association between several differentially expressed genes (DEGs) and overall survival was identified. Functional enrichment analysis of the DEGs showed that they were primarily enriched in the immune response, inflammatory response, and cytokine activity, and were involved in signaling processes related to hematopoietic cell lineage, B cell receptor, and chemokine pathways. Two significant modules, dominated respectively by CCR5 and ITGAM nodes, were identified from the PPI network, and 20 hub genes were extracted. A total of 112 DEGs correlated with poor overall survival of AML patients, and 11 of those genes were validated in a separate TARGET-AML cohort. By identifying TME-associated genes, our findings may lead to improved prognoses and therapies for AML.

Lung squamous cell carcinoma (LSCC) is the most common subtype of non-small cell lung cancer. Immunotherapy has become an effective treatment in recent years, while patients showed different responses to the current treatment. It is vital to identify the potential immunogenomic signatures to predict patient' prognosis. The expression profiles of LSCC patients with the clinical information were downloaded from TCGA database. Differentially expressed immune-related genes (IRGs) were extracted using edgeR algorithm, and functional enrichment analysis showed that these IRGs were primarily enriched in inflammatory-and immune-related processes. "Cytokinecytokine receptor interaction" and "PI3K-AKT signaling pathway" were the most enriched KEGG pathways. 27 differentially expressed IRGs were significantly correlated with the overall survival (OS) of patients using univariate Cox regression analysis. A prognostic risk signature that comprises seven IRGs (GCCR, FGF8, CLEC4M, PTH, SLC10A2, NPPC, and FGF4) was developed with effective predictive performance by multivariable Cox stepwise regression analysis. Most importantly, the signature could be an independent prognostic predictor after adjusting for clinicopathological parameters, and also validated in two independent LSCC cohorts (GSE4573 and GSE17710). Potential molecular mechanisms and tumor immune landscape of these IRGs were investigated through computational biology. Analysis of tumor infiltrating lymphocytes and immune checkpoint molecules revealed distinct immune landscape in high-and low-risk group. The study was the first time to construct IRG-based immune signature in the recognition of disease progression and prognosis of LSCC patients.