Integrative analysis of cancer-associated fibroblast signature in gastric cancer.

Background: CAFs regulate the signaling of GC cells by promoting their migration, invasion, and proliferation and the function of immune cells as well as their location and migration in the TME by remodeling the extracellular matrix (ECM). This study explored the understanding of the heterogeneity of CAFs in TME and laid the groundwork for GC biomarker and precision treatment development. Methods: The scRNA-seq and bulk RNA-seq datasets were obtained from GEO and TCGA. The prognostic significance of various CAFs subtypes was investigated using ssGSEA combined with Kaplan-Meier analysis. POSTN expression in GC tissues and CAFs was detected using immunohistochemistry, immunofluorescence, and Western blotting. Differential expression analysis identified the differentially expressed genes (DEGs) between normal and tumor samples in TCGA-STAD. Pearson correlation analysis identified DEGs associated with adverse prognosis CAF subtype, and univariate Cox regression analysis determined prognostic genes associated with CAFs. LASSO regression analysis and Multivariate Cox regression were used to build a prognosis model for CAFs. Results: We identified five CAFs subtypes in GC, with the CAF_0 subtype associated with poor prognosis. The abundance of CAF_0 correlated with T stage, clinical stage, histological type, and immune cell infiltration levels. Periostin (POSTN) exhibited increased expression in both GC tissues and CAFs and was linked to poor prognosis in GC patients. Through LASSO and multivariate Cox regression analysis, three genes (CXCR4, MATN3, and KIF24) were selected to create the CAFs-score. We developed a nomogram to facilitate the clinical application of the CAFs-score. Notably, the CAFs signature showed significant correlations with immune cells, stromal components, and immunological scores, suggesting its pivotal role in the tumor microenvironment (TME). Furthermore, CAFs-score demonstrated prognostic value in assessing immunotherapy outcomes, highlighting its potential as a valuable biomarker to guide therapeutic decisions. Conclusion: CAF_0 subtype in TME is the cause of poor prognosis in GC patients. Furthermore, CAFs-score constructed from the CAF_0 subtype can be used to determine the clinical prognosis, immune infiltration, clinicopathological characteristics, and assessment of personalized treatment of GC patients.

Neutrophil extracellular traps-related signature predicts the prognosis and immune infiltration in gastric cancer.

Introduction: Gastric cancer (GC) is the fifth most prevalent cancer globally, with the third highest case fatality rate. Neutrophil extracellular traps (NETs) are a reticulated structure of DNA, histones, and antimicrobial peptides produced by active neutrophils that trap pathogens. Even though NETs are associated with poorer recurrence-free survival (RFS) and overall survival (OS), the specifics of this interaction between NETs and cancer cells are yet unknown. Methods: The keywords "neutrophil extracellular traps and gastric cancer" were used in the GEO database for retrieval, and the GSE188741 dataset was selected to obtain the NETs-related gene. 27 NETs-related genes were screened by univariate Cox regression analysis (p < 0.05). 27 NETs-related genes were employed to identify and categorize NETs-subgroups of GC patients under the Consensus clustering analysis. 808 GC patients in TCGA-STAD combined with GES84437 were randomly divided into a training group (n = 403) and a test group (n = 403) at a ratio of 1:1 to validate the NETs-related signature. Results: Based on Multivariate Cox regression and LASSO regression analysis to develop a NETs-related prognosis model. We developed a very specific nomogram to improve the NETs-clinical score's usefulness. Similarly, we also performed a great result in pan-cancer study with NETs-score. Low NETs scores were linked to higher MSI-H (microsatellite instability-high), mutation load, and immune activity. The cancer stem cell (CSC) index and chemotherapeutic treatment sensitivity were also connected to the NET score. Our comprehensive analysis of NETs in GC suggests that NETs have a role in the tumor microenvironment, clinicopathological features, and prognosis. Discussion: The NETs-score risk model provides a basis for better prognosis and therapy outcomes in GC patients.

Whole exome sequencing of well-differentiated liposarcoma and dedifferentiated liposarcoma in older woman: a case report.

Background: Common kinds of soft tissue sarcomas (STS) include well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS). In this case, we present a comprehensive clinical profile of a patient who underwent multiple recurrences during the progression from WDLPS to DDLPS. Case presentation: A 62-year-old Asian female underwent retroperitoneal resection of a large tumor 11 years ago, the initial pathology revealed a fibrolipoma-like lesion. Over the next six years, the patient underwent three resections for recurrence of abdominal tumors. Postoperative histology shows mature adipose tissue with scattered "adipoblast"-like cells with moderate-to-severe heterogeneous spindle cells, pleomorphic cells, or tumor giant cells. Immunohistochemistry (IHC) demonstrated positive staining for MDM2 and CDK4, confirming that the abdominal tumor was WDLPS and gradually progressing to DDLPS. Post-operative targeted sequencing and IHC confirmed the POC1B::ROS1 fusion gene in DDLPS. Whole-exome sequencing (WES) revealed that WDLPS and DDLPS shared similar somatic mutations and copy number variations (CNVs), whereas DDLPS had more mutated genes and a higher and more concentrated amplification of the chromosome 12q region. Furthermore, somatic mutations in DDLPS were significantly reduced after treatment with CDK4 inhibitors, while CNVs remained elevated. Conclusion: Due to the high likelihood of recurrence of liposarcoma, various effective treatments should be taken into consideration even if surgery is the primary treatment for recurrent liposarcoma. To effectively control the course of the disease following surgery, combination targeted therapy may be a viable alternative to chemotherapy and radiotherapy in the treatment of liposarcoma.

The DNA damage repair-related lncRNAs signature predicts the prognosis and immunotherapy response in gastric cancer.

Background: Gastric cancer (GC) is one of the most prevalent cancers, and it has unsatisfactory overall treatment outcomes. DNA damage repair (DDR) is a complicated process for signal transduction that causes cancer. lncRNAs can influence the formation and incidence of cancers by influencing DDR-related mRNAs/miRNAs. A DDR-related lncRNA prognostic model is urgently needed to improve treatment strategies. Methods: The data of GC samples were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. A total of 588 mRNAs involved in DDR were selected from MSigDB, 62 differentially expressed mRNAs from TCGA-STAD were obtained, and 137 lncRNAs were correlated with these mRNAs. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were used to develop a DDR-related lncRNA prognostic model. Based on the risk model, the differentially expressed gene signature A/B in the low-risk and high-risk groups of TCGA-STAD was identified for further validation. Results: The prognosis model of 5 genes (AC145285.6, MAGI2-AS3, AL590705.3, AC007405.3, and LINC00106) was constructed and classified into two risk groups. We found that GC patients with a low-risk score had a better OS than those with a high-risk score. We found that the high-risk group tended to have higher TME scores. We also found that patients in the high-risk group had a higher proportion of resting CD4 T cells, monocytes, M2 macrophages, resting dendritic cells, and resting mast cells, whereas the low-risk subgroup had a greater abundance of activated CD4 T cells, follicular helper T cells, M0 macrophages, and M1 macrophages. We observed significant differences in the T-cell exclusion score, T-cell dysfunction, MSI, and TMB between the two risk groups. In addition, we found that patients treated with immunotherapy in the low-RS score group had a longer survival and a better prognosis than those in the high-RS score group. Conclusion: The prognostic model has a significant role in the TME, clinicopathological characteristics, prognosis, MSI, and drug sensitivity. We also discovered that patients treated with immunotherapy in the low-RS score group had a better prognosis. This work provides a foundation for improving the prognosis and response to immunotherapy among patients with GC.

The predictive effect of immune therapy and chemotherapy under T cell-related gene prognostic index for Gastric cancer.

Background: Gastric cancer (GC) is one of the most common malignancies in the human digestive tract. CD4+T cells can eliminate tumor cells directly through the mechanism of cytolysis, they can also indirectly attack tumor cells by regulating the tumor TME. A prognostic model of CD4+T cells is urgently needed to improve treatment strategies and explore the specifics of this interaction between CD4+T cells and gastric cancer cells. Methods: The detailed data of GC samples were downloaded from the Cancer Genome Atlas (TCGA), GSE66229, and GSE84437 datasets. CD4+ T cell-related genes were identified to construct a risk-score model by using the Cox regression method and validated with the Gene Expression Omnibus (GEO) dataset. In addition, postoperative pathological tissues of 139 gastric cancer patients were randomly selected for immunohistochemical staining, and their prognostic information were collected for external verification. Immune and molecular characteristics of these samples and their predictive efficacy in immunotherapy and chemotherapy were analysed. Results: The training set and validation set had consistent results, with GC patients of high PROC and SERPINE1 expression having poorer prognosis. In order to improve their clinical application value, we constructed a risk scoring model and established a high-precision nomogram. Low-risk patients had a better overall survival (OS) than high-risk patients, consistent with the results from the GEO cohort. Furthermore, the risk-score model can predict infiltration of immune cells in the tumor microenvironment of GC, as well as the response of immunotherapy. Correlations between the abundance of immune cells with PROC and SERPINE1 genes were shown in the prognostic model according to the training cohort. Finally, sensitive drugs were identified for patients in different risk subgroup. Conclusion: The risk model not only provides a basis for better prognosis in GC patients, but also is a potential prognostic indicator to distinguish the molecular and immune characteristics of the tumor, and its response to immune checkpoint inhibitor (ICI) therapy and chemotherapy.

The cancer-associated fibroblast-related signature predicts prognosis and indicates immune microenvironment infiltration in gastric cancer.

Background: Gastric cancer (GC) is one of the most common cancers, with a wide range of symptoms and outcomes. Cancer-associated fibroblasts (CAFs) are newly identified in the tumor microenvironment (TME) and associated with GC progression, prognosis, and treatment response. A novel CAF-associated prognostic model is urgently needed to improve treatment strategies. Methods: The detailed data of GC samples were downloaded from The Cancer Genome Atlas (TCGA), GSE62254, GSE26253, and GSE84437 datasets, then obtained 18 unique CAF-related genes from the research papers. Eight hundred eight individuals with GC were classified as TCGA or GSE84437 using consensus clustering by the selected CAF-related genes. The difference between the two subtypes revealed in this study was utilized to create the "CAF-related signature score" (CAFS-score) prognostic model and validated with the Gene Expression Omnibus (GEO) database. Results: We identified two CAF subtypes characterized by high and low CAFS-score in this study. GC patients in the low CAFS-score group had a better OS than those in the high CAFS-score group, and the cancer-related malignant pathways were more active in the high CAFS-score group, compared to the low CAFS-score group. We found that there was more early TNM stage in the low CAFS-score subgroup, while there was more advanced TNM stage in the high CAFS-score subgroup. The expression of TMB was significantly higher in the low CAFS-score subgroup than in the high CAFS-score subgroup. A low CAFS-score was linked to increased microsatellite instability-high (MSI-H), mutation load, and immunological activation. Furthermore, the CAFS-score was linked to the cancer stem cell (CSC) index as well as chemotherapeutic treatment sensitivity. The patients in the high CAFS-score subgroup had significantly higher proportions of monocytes, M2 macrophages, and resting mast cells, while plasma cells and follicular helper T cells were more abundant in the low-risk subgroup. The CAFS-score was also highly correlated with the sensitivity of chemotherapeutic drugs. The low CAFS-score group was more likely to have an immune response and respond to immunotherapy. We developed a nomogram to improve the CAFS-clinical score's usefulness. Conclusion: The CAFS-score may have a significant role in the TME, clinicopathological characteristics, prognosis, CSC, MSI, and drug sensitivity, according to our investigation of CAFs in GC. We also analyzed the value of the CAFS-score in immune response and immunotherapy. This work provides a foundation for improving prognosis and responding to immunotherapy in patients with GC.

Endoscopic Left Central Lymph Node Dissection of Thyroid Cancer: Safe, Feasible, and Relatively Easy.

Purpose. The purpose of this study was to explore the feasibility of left central lymph node dissection (CLND) in endoscopic thyroidectomy via chest-breast approach (ETCB). Methods. Retrospective analysis of 57 cases of left CLND (group A) via ETCB, 35 cases of open left CLND (group B), and 90 cases of right CLND via ETCB (Group C) were performed from October 2014 to October 2019. Surgical data, complications, and follow-up data were compared among group A and group B, group A and group C, respectively. Results. There were no significant differences between group A and group B in intraoperative blood loss, tumor size, lymph node (LN) metastasis rate, dissected LN number, metastatic LN number, serum thyroglobulin (sTg), radioactive iodine uptake (RAIU), radioactive technetium uptake (RATU), radionuclide imaging of the residual area (RITRA), and radionuclide imaging of suspicious lymph node metastasis (RISLNM). There were no significant differences between group A and group C in age, operation time, intraoperative blood loss, postoperative hospital stay, tumor size, LN metastasis rate, dissected LN number, metastatic LN number, hypoparathyroidism, sTg, RAIU, RATU, RITRA, and RISLNM. There were 5 cases of temporary recurrent laryngeal nerve (RLN) palsy and 1 case of recurrence in group C. Besides, 1 case of lymphatic leakage was in group A. Conclusion. For selected cases, endoscopic left CLND is safe, feasible, efficient, and more easier than endoscopic right CLND.

Prevalence and characteristics of gastric remnant cancer: A systematic review and meta-analysis.

The incidence and outcomes of GRC remain variable. Minority published researches have paid attention to the characteristics of GRC. This study aimed to make a systematic review and meta-analysis of the prevalence of GRC, with a focus on characteristics and survival rates of GRC. PubMed, EMBASE, and CENTRAL were searched for related clinical studies. Data were pooled using Stata 11.0, and subgroup and sensitivity analyses were performed if necessary and feasible. Moreover, SPSS (version 19.0) was used for comparing the clinical characteristics of GRC. Twenty studies were selected in this meta-analysis. The results indicated that the pooled prevalence of GRC was 2.6% (95% confidence interval (CI), 2.2-3.0%, p = 0.000). European population and American populations have a higher rate of prevalence of GRC than Chinese populations and Japan. There is no significant difference in histology and the TNM stage between the benign group and the malignant group. The five-year survival rate for GRC cases with benign primary gastric diseases is poorer than the primary gastric diseases malignant. Gastric remnant cancer is not a very rare clinical problem, especially for European and American patients. Active treatment and regular follow-up are conductive to increase 5-years survival rate.

Bile acid, glucose, lipid profile, and liver enzyme changes in prediabetic patients 1 year after sleeve gastrectomy.

BACKGROUND: Few articles have studied individuals with prediabetes after sleeve gastrectomy. Bile acid and lipid levels remain inconsistent in postbariatric patients. The purpose of this study was to explore bile acid, glucose, lipid, and liver enzyme changes in patients with different diabetes statuses who underwent sleeve gastrectomy. The impact of bariatric surgery and its potential benefits for prediabetic patients was also discussed. METHODS: A total of 202 overweight and obese patients who underwent bariatric surgery in our hospital between January 2016 and October 2018 were retrospectively reviewed. Patients were divided into prediabetes (n = 32), nondiabetes (n = 144), and diabetes (n = 26) groups and analysed. Glucose and lipid data were collected from medical records at baseline and at each follow-up visit. RESULT: Significant improvements in body weight, glucose and lipid levels, and liver enzymes (P ≤ 0.05) in prediabetic patients were found throughout the first year postoperatively. Improvement in glycaemic control was first seen one month postoperatively, followed by persistent improvement in the next 12 months. Total bile acid (TBA) decreased, which was associated with ALT improvement in prediabetic patients 1-year post-surgery. There were no significant differences in HbA1c, glucose, or triglycerides (TGs) between prediabetic and T2DM patients or between prediabetic and nondiabetic patients at 12 months post-surgery. CONCLUSION: LSG is highly effective at interfering with glucose and lipid levels as well as total bile acid levels in prediabetic patients in the first year postoperatively. Thus, LSG is indeed an alternative for overweight and obese prediabetic patients.

Effect of Bariatric Surgery on Serum Enzyme Status in Obese Patients.

BACKGROUND: Scarce data exists about serum enzyme in bariatric patients. We attempted to evaluate serum enzyme status in patients receiving Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) and to identify related predictors. METHODS: We retrospectively reviewed the patients receiving RYGB and SG in our center from January 2013 to January 2018. Anthropometric data and serum enzyme data were collected preoperatively and 6 and 12 months postoperatively. RESULTS: Five hundred patients (201 RYGB, 299 SG) were included. Serum enzyme abnormalities were common preoperatively, with 50.8% for elevated alanine aminotransferase (ALT), 33.0% for elevated aspartate aminotransferase (AST), 36.6% for elevated γ-glutamyltranspeptidase (γ-GT), 17.6% for elevated creatine kinase (CK), 15.2% for elevated lactic dehydrogenase (LDH), 9.0% for elevated adenosine deaminase (ADA), 6.2% for elevated hydroxybutyrate dehydrogenase (HBDH), and 8.4% for decreased superoxide dismutase (SOD). After RYGB and SG, the prevalence of serum ALT, AST, γ-GT, LDH, and HBDH abnormalities reduced. The levels of ALT, AST, γ-GT, ADA, cholinesterase (CHE), LDH, CK, and HBDH reduced significantly, while amylase and SOD levels increased. Age and preoperative γ-GT level were independent predictors of ALT, AST, γ-GT, and LDH change 1 year postoperatively. Preoperative ALT, AST, ALP, LDH, and HBDH levels could predict postoperative change, respectively. Gender and surgical procedure could predict postoperative ALP change. CONCLUSION: Serum enzyme abnormalities are common in bariatric surgery candidates, with reduced prevalence of abnormalities postoperatively. RYGB and SG are related with reduced ALT, AST, γ-GT, ADA, CHE, LDH, CK, and HBDH levels, as well as increased amylase and SOD levels.

Different surgical techniques that influenced internal hernia prevalence rate after laparoscopic roux-en-Y gastric bypass: a retrospective analysis of 331 cases.

BACKGROUND: Internal hernia (IH) is a serious complication following laparoscopic Roux-en-Y gastric bypass (LRYGB), and closure of mesenteric defect has been recommended to reduce this complication. But what kind of material about suture and how to close the mesenteric defects were still controversial. The main aim of this study was to compare the incidence rate of internal hernia after LRYGB between patients with different surgical techniques. METHOD: Three hundred and thirty-one patients underwent LRYGB between June 2004 and December 2017 in one single institute were retrospective analysed. The IH rate was evaluated according to different surgical methods and surgical materials before and 12 months after LRYGB. RESULTS: All the cases were subdivided into three groups based on the suturing method, Roux limb position, and Suture material. The mean follow up time was 36 ± 12 months, and the total incident rate of IH was 1.8% (n = 6). In the six IH cases, the duration of IH occurred time ranged from 1 month to 36 months postoperatively, and for the IH sites, one for intestinal defect, three for transverse mesocolon defect and two Peterson defect respectively. There was a significant difference about IH rate between interrupted suture and running suture groups (p = 0.011), and there were no significant differences between the other two groups. CONCLUSION: Compare with interrupted suture, running suture may prevent IH after LRYGB. Patient's gender, age, body mass index(BMI), glycometabolism condition, and Roux limb position and suture material had no effects on the IH prevalence after LRYGB.

Right Central Lymph Node Dissection in Thyroidectomy: Can Endoscopic Chest-Breast Approach Be Used?

Background: The purpose of this research was to investigate the feasibility and strategies of right central lymph node dissection (CLND) in endoscopic thyroidectomy through chest-breast approach. Materials and Methods: Retrospective analysis on the conduction of 68 cases of endoscopic thyroidectomy through chest-breast approach with right side CLND (endoscopic group) and 31 cases of thyroidectomy through low-neck collar cervical approach with right side CLND (open group) from July 2014 to February 2019. The intraoperative and postoperative data were compared between the two groups. Results: All the surgeries in open group were successfully completed as well as the endoscopic group without any intraoperative conversion into open surgery. There were no difference in sizes of tumor, incidence of lymph node metastasis, number of dissected and metastatic lymph nodes, and postoperative hospitalization days between the two groups. Temporal hypoparathyroidism occurred in both groups with endoscopic group to be 24 cases and open group to be 15 cases but no case in both groups suffering from permanent hypoparathyroidism, recurrent laryngeal nerve injury, lymphatic leakage, or death. One case in endoscopic group was treated with secondary surgery for lateral cervical lymph node metastasis and no evidence of recurrence or metastasis was found in other cases during postoperative follow-up. Conclusions: With strict control in surgical indications and contraindications, endoscopic surgery is safe and feasible for selected cases with the same effect as open surgery on dissection of lymph nodes in the right central region, which is in line with the principle of radical treatment of tumors.