Hui Cai’s research while affiliated with State Key Laboratory of Medical Genetics of China and other places

Background It has been demonstrated that nintedanib can inhibit the proliferation of gastric cancer cells, but the specific mechanism of action is unclear. Objective Investigating the changes of key factors involved in gene transcription and post-transcriptional regulation during the process of treating gastric cancer with nintedanib. Methods In this study, we performed transcriptome sequencing on gastric cancer cell groups treated with nintedanib and control groups. The SUVA (Splice sites Usage Variation Analysis) software was used to identify differential alternative splicing (AS) events between the nintedanib-treated group and the control group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to assess the functional differences and pathways associated with these events. Finally, a co-expression regulatory network of differentially expressed RNA-binding proteins (RBPs) and differentially spliced genes was established. Results: A total of 915 differential AS events were identified between the two groups, and these differential genes were closely related to the apoptosis pathway. Further analysis revealed that differential RBPs (TAGLN2, TAGLN, SRSF6, PKM, SRSF2, NOC2L, IPO4, C1QBP, DHX9) may affect the anti-proliferative effect of nintedanib on gastric cancer cells by regulating downstream genes involved in cell proliferation and angiogenesis (NR4A1, BBC3, IFI27) through alternative splicing. Conclusion This study systematically identified important changes in alternative splicing and RNA-binding proteins during the process of nintedanib-induced apoptosis in gastric cancer cells. It innovatively revealed the mechanisms of action of nintedanib in gastric cancer cells and expanded the selection of new targets for gastric cancer treatment.

Lymphocyte activating gene-3 (LAG3) is a distinctive T cell co-receptor that is expressed on the surface of lymphocytes. It plays a special inhibitory immune checkpoint role due to its unique domain and signaling pattern. Our aim is to explore the correlation between LAG3 in cancers and physiological processes related to a range of cancers, as well as build LAG3-related immunity and prognostic models. By comprehensively using of datasets and methods from TCGA, GTE-x and GEO databases, cBioPortal, HPA, Kaplan-Meier Plotter, Spearman, CellMinerTM, we delved deeper into the potential impact of the LAG3 in cancer development. These include expression differences, Localization of tumor cell subsets, immune infiltration, matrix infiltration, gene mutations, DNA methylation, signaling pathways and prognosis. Furthermore, we explored LAG3 interactions with different drugs. LAG3 is highly expressed in ACC (p < 0.001), BRCA (p < 0.001), DLBC (p < 0.001), ESCA (p < 0.001), GBM (p < 0.001), HNSC (p < 0.001), KIRC (p < 0.001), LGG (p < 0.001), LUAD (p < 0.01), LUSC (p < 0.001), PAAD (p < 0.001), PCPG (p < 0.01), SKCM (p < 0.001), STAD (p < 0.001), TGCT (p < 0.001) and THCA (p < 0.05), while lowly expressed in COAD (p < 0.001), LIHC (p < 0.05), OV (p < 0.001), PRAD (p < 0.001), READ (p < 0.001), UCEC (p < 0.001) and UCS (p < 0.001). High expression of LAG3 correlates with longer overall survival (OS) in BLCA (HR = 0.67, p < 0.05), CESC (HR = 0.3, p < 0.001), HNSC (HR = 0.67, p < 0.01), LUSC (HR = 0.71, p < 0.05), OV (HR = 0.65, p < 0.01), STAD (HR = 0.68, p < 0.05), and UCEC (HR = 0.57, p < 0.01). Conversely, in KIRC (HR = 1.85, p < 0.001), KIRP (HR = 2.81, p < 0.001), and THYM (HR = 8.92, p < 0.001), high LAG3 expression corresponds to shorter OS. Comprehensive results for recurrence-free survival (RFS) indicate that LAG3 acts as a protective factor in BLCA, CESC, OV, and UCEC. Moreover, LAG3 is widely expressed in tumor-associated lymphocytes, positively correlating with tumor immune scores and stromal scores, and significantly present in the C2 immune subtype across various tumors. High LAG3 expression correlates with increased immune infiltration. LAG3 shows associations with MSI, TMB, and the MMR system, participating in multiple signaling pathways including the T cell receptor pathway. It also demonstrates positive correlations with sensitivity to eleven different drugs. Unlike traditional inhibitory immune checkpoints, LAG3 exhibits dual roles in clinical and immune prognostication across pan-cancers, making it a significant predictive factor. In some cancers, LAG3 serves as a risk factor, indicating adverse clinical outcomes. Conversely, in BLCA, CESC, OV, and UCEC, LAG3 acts as a protective factor associated with longer patient survival. LAG3 demonstrates strong associations within tumor immunity, participating in a range of immune and inflammatory signaling pathways. Elevated levels of LAG3 are linked not only to T cell exhaustion but also to increased immune infiltration and polarization towards M1 macrophages.

Background Breast cancer (BC) is the most common cancer in women, and its progression is closely related to the phenomenon of anoikis. Anoikis, the specific programmed death resulting from a lack of contact between cells and the extracellular matrix, has recently been recognized as playing a critical role in tumor initiation, maintenance, and treatment. The ability of cancer cells to resist anoikis leads to cancer progression and metastatic colonization. However, the impact of anoikis on the prognosis of BC patients remains unclear. Method This study utilized data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to collect transcriptome and clinical data of BC patients. Anoikis-related genes (ARGs) were classified into subtypes A and B through consensus clustering. Subsequently, survival prognosis analysis, immune cell infiltration analysis, and functional enrichment analysis were performed for both subtypes. Using the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, a set of 10 ARGs related to prognosis was identified. Immune cell infiltration and tumor microenvironment analyses were conducted on these 10 ARGs to develop a prognostic model. Furthermore, single-cell data analysis and real-time polymerase chain reaction (RT-PCR) analysis were employed to study the expression of the 10 identified prognostic ARGs in BC cells. Results One hundred thirty-five ARGs were identified as differentially expressed genes in the TCGA and GEO databases, with 42 of them associated with the survival prognosis of BC patients. Analyses involving Principal Component Analysis (PCA), t-Distributed Stochastic Neighbor Embedding (t-SNE), and Uniform Manifold Approximation and Projection (UMAP) revealed distinct expression patterns of ARGs between types A and B. Patients in type A exhibited worse survival prognosis and lower immune cell infiltration compared to type B. Subsequent analyses identified 10 key ARGs (YAP1, PIK3R1, BAK1, PHLDA2, EDA2R, LAMB3, CD24, SLC2A1, CDC25C, and SLC39A6) relevant to BC prognosis. Kaplan–Meier analysis indicated that high-risk patients based on these ARGs had a poorer BC prognosis. Additionally, Cox regression analysis established gender, age, T (tumor), N (nodes), and risk score as predictive factors in a nomogram model for BC. The model demonstrated diagnostic value for BC patients at 1, 3, and 5 years. Decision curve analysis (DCA) verified the risk score as a reliable predictor of BC patient survival rates. Moreover, RT-PCR results confirmed differential expressions of YAP1, PIK3R1, BAK1, PHLDA2, CD24, SLC2A1, and CDC25C in BC cells, with SLC39A6, EDA2R, and LAMB3 showing low expression levels. Conclusion ARGs markers can be used as BC biomarkers for risk stratification and survival prediction in BC patients. Besides, ARGs can be used as stratification factors for individualized and precise treatment of BC patients.

Background With the popularization of robotic surgical systems in the field of surgery, robotic gastric cancer surgery has also been fully applied and promoted in China. The Chinese Guidelines for Robotic Gastric Cancer Surgery was published in the Chinese Journal of General Surgery in August 2021. Methods We have made a detailed interpretation of the process of robotic gastric cancer surgery regarding the indications, contraindications, perioperative preparation, surgical steps, complication, and postoperative management based on the recommendations of China’s Guidelines for Robotic Gastric Cancer Surgery and supplemented by other surgical guidelines, consensus, and single-center experience. Results Twenty experiences of perioperative clinical management of robotic gastric cancer surgery were described in detail. Conclusion We hope to bring some clinical reference values to the front-line clinicians in treating robotic gastric cancer surgery. Trial registration The guidelines were registered on the International Practice Guideline Registration Platform (http://www.guidelines-registry.cn) (registration number: IPGRP-2020CN199).

Background Underlying liver disease is correlated with hepatocellular carcinoma (HCC) development in patients with hepatitis B virus (HBV) infection. However, the impact of hepatic inflammation and fibrosis on the patients’ prognoses remains unclear. Methods The clinicopathological data of 638 HBV-infected patients with early-stage HCC between 2017 and 2019 were prospectively collected. Hepatic inflammation and fibrosis were evaluated by experienced pathologists using the Scheuer score system. Survival analysis was analyzed using the Kaplan–Meier analysis. Results Application of the Scheuer scoring system revealed that 50 (7.9%), 274 (42.9%), and 314 (49.2%) patients had minor, intermediate, and severe hepatic inflammation, respectively, and 125 (15.6%), 150 (23.5%), and 363 (56.9%) patients had minor fibrosis, advanced fibrosis, and cirrhosis, respectively. Patients with severe hepatitis tended to have a higher rate of HBeAg positivity, higher HBV-DNA load, elevated alanine aminotransferase (ALT) levels, and a lower proportion of capsule invasion (all Pp < 0.05). There were no significant differences in the recurrence-free and overall survival among the three groups (P = 0.52 and P = 0.66, respectively). Patients with advanced fibrosis or cirrhosis had a higher proportion of HBeAg positivity and thrombocytopenia, higher FIB-4, and larger tumor size compared to those with minor fibrosis (all P < 0.05). Patients with minor, advanced fibrosis, and cirrhosis had similar prognoses after hepatectomy (P = 0.48 and P = 0.70). The multivariate analysis results indicated that neither hepatic inflammation nor fibrosis was an independent predictor associated with prognosis. Conclusions For HBV-related HCC patients receiving antiviral therapy, hepatic inflammation and fibrosis had little impact on the post-hepatectomy prognosis.

Background: There is an ongoing debate regarding the comparative merits of splenectomy (SP) and splenic preservation in the surgical management of gastric cancer. This systematic review and meta-analysis aims to shed light on potential differences in survival outcomes and postoperative complications associated with these two procedures. Method: An exhaustive literature search was conducted across multiple databases, namely PubMed, Embase, Cochrane Library, and Web of Science. We utilized a random-effects model via RevMan 5.4 software to conduct a meta-analysis of the hazard ratios (HRs) and risk ratios (RRs) associated with SP and spleen preservation. Subgroup analyses were based on various attributes of the included studies. We employed funnel plots to assess publication bias, and sensitivity analysis was conducted to gauge the stability of the combined results. Both funnel plots and sensitivity analysis were performed using Stata 12. Result: Our research incorporated 23 observational studies and three randomized controlled trials, involving a total of 6,255 patients. SP did not yield superior survival outcomes in comparison to splenic preservation, a conclusion that aligns with the combined results of the randomized controlled trials. No statistically significant difference in survival prognosis was observed between SP and splenic preservation, irrespective of whether the patients had proximal gastric cancer or proximal gastric cancer invading the stomach's greater curvature. SP exhibited a higher incidence of all postoperative complications, notably pancreatic fistula and intraabdominal abscesses. However, it did not significantly differ from splenic preservation in terms of anastomotic leakage, incision infection, intestinal obstruction, intra-abdominal bleeding, and pulmonary infection. No significant difference in postoperative mortality between SP and splenic preservation was found. Funnel plots suggested no notable publication bias, and sensitivity analysis affirmed the stability of the combined outcomes. Conclusion: Despite the lack of significant differences in certain individual complications and postoperative mortality, the broader pattern of our data suggests that SP is associated with a greater overall frequency of postoperative complications, without providing additional survival benefits compared to splenic preservation. Thus, the routine implementation of SP is not advocated.

Objective It has been demonstrated that IDO1, a target of immune checkpoint inhibition, functions as an oncogene in the majority of human malignancies. IDO1’s function in human pan-cancers hasn’t been thoroughly studied, though. Materials and methods The Kaplan–Meier (K-M) and COX analyses were applied to the survival analysis. Furthermore, we used Spearman’s correlation analysis to examine the associations between IDO1 and microsatellite instability (MSI), DNA methyltransferases (DNMTs), tumor mutational burden (TMB), the associated genes of mismatch repair (MMR), and immune checkpoint biomarkers. Moreover, immunohistochemical analysis and qRT-PCR were used to evaluate IDO1’s expression in pan-cancer cells. Results The findings of this study reveal that IDO1 has abnormal expression in a number of malignancies and is related to the prognosis for UVM, LGG, KIRP, GBM, LAML, OV, READ, MESO, SARC, SKCM, and HNSC. Furthermore, the aberrant IDO1 expression was connected to the TMB, MSI, MMR, drug sensitivity, immune cells infiltrating, and tumor immune microenvironment across a variety of cancer types. The PCR results showed that in contrast to normal cells, IDO1 was found to be significantly highly expressed in breast cancer cells and hepatocellular carcinoma cells, and significantly lowly expressed in gastric cancer cells. Conclusion The clinical treatment of IDO1 is now better supported by a theoretical basis and guidelines provided by our study.

Diabetic wounds are a type of wound that is characterized by protracted and refractory. In recent years, the use of mesenchymal stem cell-derived exosome(MSC-Exo)in wound treatment has made certain progress, especially bone marrow mesenchymal stem cell exosome (BMSC-Exo༉also have get achievement in wound treatment, and this paper aims to study whether bone marrow mesenchymal stem cell-derived exosomes can promote the healing of diabetic wound and its mechanism. We conducted in vivo and in vitro experiments to verify whether BMSC-Exo can promote wound healing and promote the proliferation and migration of fibroblasts after high glucose treatment in diabetic rats. The expression of NLRP3, IL-18, IL-1β, caspase-1,and GSDMD proteins in rats and cells in each group was detected to verify the relationship between the mechanism of BMSC-Exo promoting wound healing and cell pyroptosis. The results showed that BMSCs-Exo can significantly improve the wound healing rate in diabetic rats and promote the proliferation and migration of fibroblast under high glucose conditions. At the same time, we confirmed that the pyroptosis in diabetic rat wound and fibroblast in high sugar was significantly increased, and BMSCs-Exo could significantly inhibit the pyroptosis in diabetic rat wound and fibroblast. These results suggest that BMSC-Exo inhibits cell pyroptosis through NLRP3/ caspase-1/GSDMD pathway in vivo and in vitro, and promotes wound healing in diabetic rats.

BACKGROUND Gastric cancer has a high incidence and fatality rate, and surgery is the preferred course of treatment. Nonetheless, patient survival rates are still low, and the incidence of major postoperative complications cannot be disregarded. The systemic inflammatory response, nutritional level, and coagulation status are key factors affecting the postoperative recovery and prognosis of gastric cancer patients. The systemic inflammatory response index (SIRI) and the albumin fibrinogen ratio (AFR) are two valuable comprehensive indicators of the severity and prognosis of systemic inflammation in various medical conditions. AIM To assess the clinical importance and prognostic significance of the SIRI scores and the AFR on early postoperative outcomes in patients undergoing radical gastric cancer surgery. METHODS We conducted a retrospective analysis of the clinicopathological characteristics and relevant laboratory indices of 568 gastric cancer patients from January 2018 to December 2019. We calculated and compared two indicators of inflammation and then examined the diagnostic ability of combined SIRI and AFR values for serious early postoperative complications. We scored the patients and categorized them into three groups based on their SIRI and AFR levels. COX analysis was used to compare the three groups of patients the prognostic value of various preoperative SIRI-AFR scores for 5-year overall survival (OS) and disease-free survival (DFS). RESULTS SIRI-AFR scores were an independent risk factor for prognosis [OS: P = 0.004; hazards ratio (HR) = 3.134; DFS: P < 0.001; HR = 3.543] and had the highest diagnostic power (area under the curve: 0.779; 95% confidence interval: 0.737-0.820) for early serious complications in patients with gastric cancer. The tumor-node-metastasis stage (P = 0.001), perioperative transfusion (P = 0.044), positive carcinoembryonic antigen (P = 0.014) findings, and major postoperative complications (P = 0.011) were factors associated with prognosis. CONCLUSION Preoperative SIRI and AFR values were significantly associated with early postoperative survival and the occurrence of severe complications in gastric cancer patients.

Background The hypercoagulable state of cancer patients is associated with their high mortality rate. Coagulation indicators may have an important role in the prognosis of gastric cancer patients and deserve to be explored in various aspects. Objective We conducted a meta-analysis to explore the correlation between coagulation and prognosis of gastric cancer. Methods A comprehensive systematic search was conducted in PubMed, Embase, Web of Science databases, and the Cochrane Library up to February 16, 2024. Literature screening and data extraction were performed by two independent reviewers. The processed data we pooled using either a random-effects model or a fixed-effects model and finally described overall survival with a risk ratio (hazard ratio [HR]) and predicted the likelihood of different clinicopathological events with a dominance ratio (OR). Results A total of 64 studies were screened for inclusion in the data analysis. Performing a meta-analysis of three indicators we derived that the risk of d-dimer (D-D), fibrinogen (FIB), and platelets (PLTs) were: HR = 1.85 (95% confidence interval [CI]: 1.59–2.15, N = 15), HR = 1.77 (95% CI: 1.57–1.99, N = 28), HR = 1.16 (95% CI: 1.12–1.21, N = 29). In addition to this, all three were associated with advanced clinicopathological stage (D-D: OR = 2.25, FIB: OR = 2.07, PLT: OR = 1.84), T stage (D-D: OR = 2.30, FIB: OR = 2.38, PLT: OR = 2.22) and lymph node metastasis (D-D: OR = 1.79, FIB: OR = 1.70, PLT: OR = 1.51). Conclusion Overall, the findings suggest that the three indicators, D-D, FIB, and PLT count, have significant predictive value for the prognosis of gastric cancer. They were associated with an advanced clinicopathological stage and a high risk of lymph node metastasis.