Wenhao Sun

Background/Objectives: Patients with ulcerative colitis (UC) carry a substantially elevated risk of developing colorectal cancer (CRC); yet, the transcriptional intermediates that bridge chronic mucosal inflammation and colorectal malignancy remain poorly characterized. A related question is whether any genes shared between the two conditions actually help drive transformation, or whether they represent downstream responders. Methods: We integrated two UC microarray cohorts (totalling 227 samples) and the TCGA-COAD dataset (n = 524), combining weighted gene co-expression network analysis (WGCNA) with directional differential expression to define shared candidate genes. Three machine-learning approaches—LASSO, random forest, and SVM-RFE—were applied to that candidate set, and the stability of their intersection was assessed by bootstrap resampling. The resulting panel was then examined by replication in an independent UC cohort, two-sample Mendelian randomization, immune deconvolution, survival modelling, and Visium spatial transcriptomics. Results: WGCNA and directional differential expression together yielded 91 shared candidate genes, and the three algorithms converged on four: CXCL1, S100P, THY1, and TRIM29. Bootstrap resampling showed that this convergence is a property of one particular fit rather than a reproducible selector (all four recovered together in 0.3% of 1000 resamples), so we treated the ensemble as a hypothesis-generating step and made our case for the panel based on independent downstream evidence. This evidence was consistent, as, in an independent UC cohort (GSE92415, n = 183), all four genes moved in the same direction as in discovery, and a four-gene model separated inflamed from control mucosa with a cross-validated AUC of 0.986 (95% CI 0.965–1.000). Two-sample Mendelian randomization using strong blood cis-eQTL instruments (F = 345 for CXCL1, F = 2423 for S100P) returned null estimates; for S100P, the design had 80% power to detect an odds ratio of 1.07 per standard deviation, so this is an informative null rather than an absence of data, while THY1 and TRIM29 had no cis-eQTLs in eQTLGen and remain untestable. Each gene showed a distinct pattern of immune cell correlation in TCGA-COAD. LASSO-Cox retained only CXCL1, whose higher expression was associated with a better rather than worse overall survival (HR 0.79 per SD, p = 0.020); its discrimination was weak (optimism-corrected C-index 0.56 for the score alone) and did not reach significance in an external cohort (GSE39582, n = 573; p = 0.11), so we reported no prognostic model. In Visium spatial data from four colonic sections, a three-compartment structure was reproducible between UC sections—CXCL1 near the neutrophil and interferon signals, THY1 within the stroma and anticorrelated with the epithelium, and S100P and TRIM29 alongside the epithelium—although, with two sections per group, the difference in module scores between the UC and control mucosa was not resolvable. Conclusions: Collectively, these four genes describe a spatially structured epithelial–stromal–immune module of the inflamed mucosa; however, the findings are hypothesis-generating and are not sufficient for prognostic or stratification use.

The development and metastasis of gastric cancer are complex processes involving the TME (Tumor microenvironment) and the interactions between various cell types. Here, we investigated the molecular mechanisms and biological processes underlying gastric cancer and its metastasis using single cell RNA-sequencing (scRNA-seq) with the aim of identifying new targets and approaches for clinical treatment. R version 4.4.1 and the SeuratV5 package were used to process 20 scRNA-seq samples sourced from the GEO database. Highly variable genes were selected for GO (Gene Ontology), KEGG (Kyoto Encyclopedia of Genes and Genomes) and GSAV (Gene set variation analysis) enrichment analyses. CytoTRACE, CellChat, and Monocle3 analyses were conducted to investigate cell communication and pseudotemporal dynamics in the PM (Peritoneal Metastasis) and GC (Gastric Cancer) groups. Additionally, the prognostic significance of key genes was assessed by integrating data from the TCGA clinical database. A total of 2,626,594 peritoneal metastasis cells and 17,894 gastric cancer cells were identified, revealing 13 distinct cell clusters. Gene enrichment analyses identified high expression in several pathways (P53, Wnt and JAK-STAT3) in TAMs and mast cells. Cell communication was more robust in the GC group than the PM group, with TAMs (Tumor-associated Macrophages) and mast cells showing elevated expression of the CCL5-CCR1 ligand-receptor signaling axis in both groups. Pseudotemporal analysis demonstrated the differentiation potential of TAMs into mast cells, with APOC1, C1QB, FCN1, FTL, S100A9, CD1C, CD1E and FCER1A identified as the top eight genes driving this process. High expression levels of these genes, along with CCL5 and CCR1, were associated with poor long-term survival in cancer patients. scRNA-seq identified the intricate tumor immune microenvironment, highlighting the pivotal roles of TAMs and mast cells in gastric cancer peritoneal metastasis. The CCL5-CCR1 pathway emerged as a potential immune checkpoint, offering novel insights for future immunotherapeutic and targeted therapeutic strategies in the treatment of gastric cancer peritoneal metastasis.

Background: Pancreatic cancer is one of the most aggressive malignant tumors worldwide, often resulting in poor prognosis. Smoking is widely recognized as a significant risk factor for this disease. Methods: This study extracted data on the disease burden of pancreatic cancer attributable to smoking in China from the Global Burden of Disease 2021 (GBD 2021) database. A total of 447 334 individuals were included in the analysis. A joinpoint regression model was used to calculate the annual percentage change (APC) and average annual percentage change (AAPC) to assess trends in the disease burden from 1990 to 2021. The age-period-cohort model was applied to explain the epidemiological trends of the disease by controlling for variables associated with age, period, and birth cohort. Decomposition analysis was conducted to quantify the relative contributions of population growth, population aging, and epidemiological changes. The Autoregressive Integrated Moving Average (ARIMA) model was utilized to forecast the burden of pancreatic cancer due to smoking in China over the next 15 years. Results: From 1990 to 2021, the age-standardized mortality rate (ASMR) and the age-standardized disability-adjusted life years rate (ASDR) due to smoking-related pancreatic cancer in China exhibited an upward trend. By 2021, the total number of deaths and disability-adjusted life years (DALYs) had almost doubled compared to 1990. The mortality and DALY rates increased with age, peaking at approximately 85 years and 70 years, respectively, indicating a substantial burden on the elderly population. Furthermore, we predict that female ASMR and ASDR may start to decline in the next 15 years; however, the absolute burden remains unchanged. Conversely, the ASMR and ASDR for males continue to rise, indicating an increasing burden, with the male burden consistently surpassing that of females. Conclusions: This study demonstrates that from 1990 to 2021, the burden of pancreatic cancer attributable to smoking in China has intensified, with significant disparities related to sex and age. The future outlook appears quite severe, given the large population base and accelerating population aging. Strong smoking cessation and control measures specifically targeting elderly males are imperative to limit tobacco exposure among high-risk groups, as these measures are crucial for alleviating the burden of pancreatic cancer in China.

BackgroundPancreatic cancer is one of the most aggressive malignant tumors worldwide, often resulting in poor prognosis. Smoking is widely recognized as a significant risk factor for this disease.MethodsThis study extracted data on the disease burden of pancreatic cancer attributable to smoking in China from the Global Burden of Disease 2021 (GBD 2021) database. A total of 447 334 individuals were included in the analysis. A joinpoint regression model was used to calculate the annual percentage change (APC) and average annual percentage change (AAPC) to assess trends in the disease burden from 1990 to 2021. The age-period-cohort model was applied to explain the epidemiological trends of the disease by controlling for variables associated with age, period, and birth cohort. Decomposition analysis was conducted to quantify the relative contributions of population growth, population aging, and epidemiological changes. The Autoregressive Integrated Moving Average (ARIMA) model was utilized to forecast the burden of pancreatic cancer due to smoking in China over the next 15 years.ResultsFrom 1990 to 2021, the age-standardized mortality rate (ASMR) and the age-standardized disability-adjusted life years rate (ASDR) due to smoking-related pancreatic cancer in China exhibited an upward trend. By 2021, the total number of deaths and disability-adjusted life years (DALYs) had almost doubled compared to 1990. The mortality and DALY rates increased with age, peaking at approximately 85 years and 70 years, respectively, indicating a substantial burden on the elderly population. Furthermore, we predict that female ASMR and ASDR may start to decline in the next 15 years; however, the absolute burden remains unchanged. Conversely, the ASMR and ASDR for males continue to rise, indicating an increasing burden, with the male burden consistently surpassing that of females.ConclusionsThis study demonstrates that from 1990 to 2021, the burden of pancreatic cancer attributable to smoking in China has intensified, with significant disparities related to sex and age. The future outlook appears quite severe, given the large population base and accelerating population aging. Strong smoking cessation and control measures specifically targeting elderly males are imperative to limit tobacco exposure among high-risk groups, as these measures are crucial for alleviating the burden of pancreatic cancer in China.