Kaplan-Meier Research Articles

Albumin–bilirubin grade as a predictor of survival in hepatocellular carcinoma patients with thrombocytopenia

BACKGROUND The models for assessing liver function, mainly the Child–Pugh (CP), albumin–bilirubin (ALBI), and platelet–ALBI (PALBI) classifications, have been validated for use in estimating the prognosis of hepatocellular carcinoma (HCC) patients. However, thrombocytopenia is a common finding and may influence the prognostic value of the three models in HCC. AIM To investigate and compare the prognostic performance of the above three models in thrombocytopenic HCC patients. METHODS A total of 135 patients with thrombocytopenic HCC who underwent radical surgery were retrospectively analyzed. Preoperative scores on the CP, ALBI and PALBI classifications were estimated accordingly. Kaplan–Meier curves with log-rank tests and Cox regression models were used to explore the significant factors associated with overall survival (OS) and recurrence-free survival (RFS). RESULTS The preoperative platelet counts were significantly different among the CP, ALBI and PALBI groups. After a median follow-up of 28 mo, 39.3% (53/135) of the patients experienced postoperative recurrence, and 36.3% (49/135) died. Univariate analysis suggested that α-fetoprotein levels, tumor size, vascular invasion, and ALBI grade were significant predictors of OS and RFS. According to the multivariate Cox regression model, ALBI was identified as an independent prognostic factor. However, CP and PALBI grades were not statistically significant prognostic indicators. CONCLUSION The ALBI grade, rather than CP or PALBI grade, is a significant prognostic indicator for thrombocytopenic HCC patients.

Identification of differentially expressed mRNAs as novel predictive biomarkers for gastric cancer diagnosis and prognosis

BACKGROUND Gastric cancer (GC) has a high mortality rate worldwide. Despite significant progress in GC diagnosis and treatment, the prognosis for affected patients still remains unfavorable. AIM To identify important candidate genes related to the development of GC and identify potential pathogenic mechanisms through comprehensive bioinformatics analysis. METHODS The Gene Expression Omnibus database was used to obtain the GSE183136 dataset, which includes a total of 135 GC samples. The limma package in R software was employed to identify differentially expressed genes (DEGs). Thereafter, enrichment analyses of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for the gene modules using the clusterProfile package in R software. The protein-protein interaction (PPI) networks of target genes were constructed using STRING and visualized by Cytoscape software. The common hub genes that emerged in the cohort of DEGs that was retrieved from the GEPIA database were then screened using a Venn Diagram. The expression levels of these overlapping genes in stomach adenocarcinoma samples and non-tumor samples and their association with prognosis in GC patients were also obtained from the GEPIA database and Kaplan-Meier curves. Moreover, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were performed to determine the mRNA and protein levels of glutamic-pyruvic transaminase (GPT ) in GC and normal immortalized cell lines. In addition, cell viability, cell cycle distribution, migration and invasion were evaluated by cell counting kit-8, flow cytometry and transwell assays. Furthermore, we also conducted a retrospective analysis on 70 GC patients diagnosed and surgically treated in Wenzhou Central Hospital, Dingli Clinical College of Wenzhou Medical University, The Second Affiliated Hospital of Shanghai University between January 2017 to December 2020. The tumor and adjacent normal samples were collected from the patients to determine the potential association between the expression level of GPT and the clinical as well as pathological features of GC patients. RESULTS We selected 19214 genes from the GSE183136 dataset, among which there were 250 downregulated genes and 401 upregulated genes in the tumor samples of stage III-IV in comparison to those in tumor samples of stage I-II with a P -value < 0.05. In addition, GO and KEGG results revealed that the various upregulated DEGs were mainly enriched in plasma membrane and neuroactive ligand-receptor interaction, whereas the downregulated DEGs were primarily enriched in cytosol and pancreatic secretion, vascular smooth muscle contraction and biosynthesis of the different cofactors. Furthermore, PPI networks were constructed based on the various upregulated and downregulated genes, and there were a total 15 upregulated and 10 downregulated hub genes. After a comprehensive analysis, several hub genes, including runt-related transcription factor 2 (RUNX2 ), salmonella pathogenicity island 1 (SPI1 ), lysyl oxidase (LOX ), fibrillin 1 (FBN1 ) and GPT , displayed prognostic values. Interestingly, it was observed that GPT was downregulated in GC cells and its upregulation could suppress the malignant phenotypes of GC cells. Furthermore, the expression level of GPT was found to be associated with age, lymph node metastasis, pathological staging and distant metastasis (P < 0.05). CONCLUSION RUNX2 , SPI1 , LOX , FBN1 and GPT were identified key hub genes in GC by bioinformatics analysis. GPT was significantly associated with the prognosis of GC, and its upregulation can effectively inhibit the proliferative, migrative and invasive capabilities of GC cells.

MiRNA-145-5p inhibits gastric cancer progression via the serpin family E member 1- extracellular signal-regulated kinase-1/2 axis

BACKGROUND MicroRNAs (miRNAs) regulate gene expression and play a critical role in cancer physiology. However, there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer (GC). AIM To investigate the role and molecular mechanism of miRNA-145-5p (miR145-5p ) in the progression of GC. METHODS Real-time polymerase chain reaction (RT-PCR) was used to detect miRNA expression in human GC tissues and cells. The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays, respectively. Cell proliferation was measured using cell counting kit-8 and colony formation assays, and apoptosis was evaluated using flow cytometry. Expression of the epithelial-mesenchymal transition (EMT)-associated protein was determined by Western blot. Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system. Serpin family E member 1 (SERPINE1 ) expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining. The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis. The association between SERPINE1 and GC progression was also tested. A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p . The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice. RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA. Overexpression of miR-145-5p was associated with decreased GC cell proliferation, invasion, migration, and EMT, and these effects were reversed by forcing SERPINE1 expression. Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression. Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2 (ERK1/2). CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC. MiR-145-5p was found to affect GC cell proliferation, migration, and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.

An updated analysis of retransplantation following living donor liver transplantation in the US: insights from the latest UNOS database.

There is no recent update on the clinical course of retransplantation(re-LT) after living-donor liver transplantation (LDLT) in the US using recent national data. The UNOS database (2002-2023) was used to explore patient characteristics in initial LT, comparing deceased-donor liver transplantation (DDLT) and LDLT for graft survival (GS), reasons for graft failure, and GS after re-LT. It assesses waitlist dropout and re-LT likelihood, categorizing re-LT cohort based on time to re-listing as acute or chronic (≤ or >1mo). Of 132,323 DDLT and 5,955 LDLT initial transplants, 3,848 DDLT and 302 LDLT recipients underwent re-LT. Of the 302 re-LT following LDLT, 156 were acute and 146 chronic. Primary non-function (PNF) was more common in DDLT, although the difference was not statistically significant (17.4%vs14.8% for LDLT; p=0.52). Vascular complications were significantly higher in LDLT (12.5%vs8.3% for DDLT; p<0.01). Acute re-LT showed a larger difference in PNF between DDLT and LDLT (49.7%vs32.0%; p<0.01). Status 1 patients were more common in DDLT (51.3%vs34.0% in LDLT; p<0.01). In the acute cohort, Kaplan-Meier curves indicated superior GS post-re-LT for initial LDLT recipients in both short-term and long-term (p=0.02 and <0.01, respectively), with no significant difference in the chronic cohort. No significant differences in waitlist dropout were observed, but the initial LDLT group had a higher re-LT likelihood in the acute cohort (sHR 1.40, p<0.01). A sensitivity analysis focusing on the most recent 10-year cohort revealed trends consistent with the overall study findings. LDLT recipients had better GS in re-LT than DDLT. Despite a higher severity of illness, the DDLT cohort was less likely to undergo re-LT.

Development and validation of a novel criterion of histologic healing in ulcerative colitis defined by inflammatory cell enumeration in lamina propria mucosae: A multicenter retrospective cohort in China.

Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis (UC). Here, we developed a novel diagnostic criterion for assessing histological healing in UC patients. We conducted a retrospective cohort study in UC patients, whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People's Hospital of Tongji University from January 2017 to May 2022. We identified an inflammatory cell enumeration index (ICEI) for assessing histological healing based on the proportions of eosinophils, CD177+ neutrophils, and CD40L+ T cells in the colonic lamina propria under high power field (HPF), and the outcomes (risks of symptomatic relapses) of achieving histological remission vs. persistent histological inflammation using Kaplan-Meier curves. Intrareader reliability and inter-reader reliability were evaluated by each reader. The relationships to the changes in the Nancy index and the Geboes score were also assessed for responsiveness. The ICEI was further validated in a new cohort of UC patients from other nine university hospitals. We developed an ICEI for clinical diagnosis of histological healing, i.e., Y=1.701X1 + 0.758X2 + 1.347X3 - 7.745 (X1, X2, and X3 represent the proportions of CD177+ neutrophils, eosinophils, and CD40L+ T cells, respectively, in the colonic lamina propria under HPF). The receiver operating characteristics curve (ROC) analysis revealed that Y <-0.391 was the cutoff value for the diagnosis of histological healing and that an area under the curve (AUC) was 0.942 (95% confidence interval [CI]: 0.905-0.979) with a sensitivity of 92.5% and a specificity of 83.6% (P<0.001). The intraclass correlation coefficient (ICC) for the intrareader reliability was 0.855 (95% CI: 0.781-0.909), and ICEI had good inter-reader reliability of 0.832 (95% CI: 0.748-0.894). During an 18-month follow-up, patients with histological healing had a substantially better outcome compared with those with unachieved histological healing (P<0.001) using ICEI. During a 12-month follow-up from other nine hospitals, patients with histological healing also had a lower risk of relapse than patients with unachieved histological healing. ICEI can be used to predict histological healing and identify patients with a risk of relapse 12 months and 18 months after clinical therapy. Therefore, ICEI provides a promising, simplified approach to monitor histological healing and to predict the prognosis of UC. Chinese Clinical Trial Registry, No. ChiCTR2300077792.

Efficacy and safety of niraparib in platinum-sensitive recurrent ovarian cancer: retrospective observational study in a tertiary hospital.

Niraparib has been authorized for maintenance treatment of epithelial ovarian cancer after first-line treatment with platinum, in partial or complete response. To evaluate the effectiveness and safety of maintenance niraparib in platinum-sensitive recurrent ovarian cancer (PSROC) patients in a tertiary hospital. This retrospective observational unicentre study included women diagnosed with ovarian adenocarcinoma who received niraparib. Eligibility criteria encompassed women with PSROC, in response to platinum chemotherapy, and not previously treated with other PARPis. Data on demographics, comorbidities, BRCA mutation status, disease stage, treatment history and adverse events were recorded. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. A total of 33 patients were included, with a median age of 63.5 years. The majority of patients received niraparib at 200 mg/day based on Research on Adverse Drug Events and Report criteria. Median OS was 30 months (95% CI: 16.76-43.23), and median PFS was 8 months (95% CI: 2.48-13.52). Adverse effects were more frequent during the initial months of treatment, with most classified as CTCAE v5 grade 1-2. Dose reductions, interruption of treatment and discontinuations were observed due to haematologic toxicities primarily. This real-world study showed that maintenance niraparib in PSROC patients had effectiveness and safety profiles consistent with clinical trials and other observational studies. Median PFS and OS were comparable to previous reports, and most adverse events were manageable with dose modifications. The results support the use of niraparib as a maintenance therapy option in this patient population.

Association of sarcopenia with the long-term risk of atrial fibrillation: A prospective cohort study.

The relationship between sarcopenia and the long-term risk of atrial fibrillation (AF) remains unclear. This study recruited a large prospective Caucasian cohort from the UK Biobank. Participants were assessed at baseline with handgrip strength and muscle mass and were categorized into groups of non-sarcopenia, probable sarcopenia, and confirmed sarcopenia. Kaplan-Meier method and Cox proportional hazards model were used to explore the association between sarcopenia and the incidence of AF. The genetic predisposition of AF was assessed by polygenic risk score. Sensitivity analyses were performed to validate the results. A total of 384,433 participants with a median age of 58 years and 54.3% women were enrolled in this study. There were 24,007 cases of new-onset AF over a median follow-up of 12.56 years. The groups of non-sarcopenia, probable sarcopenia, and confirmed sarcopenia accounted for 22,290 (6.1%), 1665 (9.2%), and 52 (11.9%) cases, respectively. Compared with the non-sarcopenia group, participants with probable sarcopenia or confirmed sarcopenia had an 8% (95% CI, 1.03-1.14) or 61% (95% CI, 1.23-2.12) higher risk of AF incidence. The findings remained robust in multiple sensitivity analyses, such as subgroup analysis and further adjustment of genetic predisposition. Notably, the association between sarcopenia and a high AF risk was more pronounced in younger participants, women, and those with valvular heart disease. In conclusion, sarcopenia was associated with a high long-term risk of AF in Caucasians, supporting sarcopenia as a new independent risk factor of AF.

Extracellular volume-based scoring system for tracking tumor progression in pancreatic cancer patients receiving intraoperative radiotherapy

ObjectivesTo investigate the value of extracellular volume (ECV) derived from portal-venous phase (PVP) in predicting prognosis in locally advanced pancreatic cancer (LAPC) patients receiving intraoperative radiotherapy (IORT) with initial stable disease (SD) and to construct a risk-scoring system based on ECV and clinical-radiological features.Materials and methodsOne hundred and three patients with LAPC who received IORT demonstrating SD were enrolled and underwent multiphasic contrast-enhanced CT (CECT) before and after IORT. ECV maps were generated from unenhanced and PVP CT images. Clinical and CT imaging features were analyzed. The independent predictors of progression-free survival (PFS) determined by multivariate Cox regression model were used to construct the risk-scoring system. Time-dependent receiver operating characteristic (ROC) curve analysis and the Kaplan–Meier method were used to evaluate the predictive performance of the scoring system.ResultsMultivariable analysis revealed that ECV, rim-enhancement, peripancreatic fat infiltration, and carbohydrate antigen 19-9 (CA19-9) response were significant predictors of PFS (all p < 0.05). Time-dependent ROC of the risk-scoring system showed a satisfactory predictive performance for disease progression with area under the curve (AUC) all above 0.70. High-risk patients (risk score ≥ 2) progress significantly faster than low-risk patients (risk score < 2) (p < 0.001).ConclusionECV derived from PVP of conventional CECT was an independent predictor for progression in LAPC patients assessed as SD after IORT. The scoring system integrating ECV, radiological features, and CA19-9 response can be used as a practical tool for stratifying prognosis in these patients, assisting clinicians in developing an appropriate treatment approach.Critical relevance statementThe scoring system integrating ECV fraction, radiological features, and CA19-9 response can track tumor progression in patients with LAPC receiving IORT, aiding clinicians in choosing individual treatment strategies and improving their prognosis.Key PointsPredicting the progression of LAPC in patients receiving IORT is important.Our ECV-based scoring system can risk stratifying patients with initial SD.Appropriate prognostication can assist clinicians in developing appropriate treatment approaches.Graphical

Mesencephalic astrocyte-derived neurotrophic factor inhibits cervical cancer progression via regulating macrophage phenotype.

Cervical cancer is a common gynecologic malignant tumor, but the critical factors affecting cervical cancer progression are still not well demonstrated. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been widely recognized as an anti-inflammatory factor to regulate macrophage polarization. In this study, the effect and mechanism of MANF on cervical cancer were preliminarily explored. Kaplan-Meier curve was used to show the overall survival time of the involved cervical cancer patients with high and low MANF expression in cervical cancer tissues. MANF was highly expressed in peritumoral tissues of cervical carcinoma by using immunohistochemistry and western blot. MANF mRNA level was detected by using qRT-PCR. Dual-labeled immunofluorescence showed MANF was mainly expressed in macrophages of cervical peritumoral tissues. Moreover, MANF-silenced macrophages promoted HeLa and SiHa cells survival, migration, invasion and EMT via NF-κB signaling activation. The results of tumor formation in nude mice indicated MANF-silenced macrophages promoted cervical tumor formation in vivo. Our study reveals an inhibitory role of MANF in cervical cancer progression, indicating MANF as a new and valuable therapeutic target for cervical cancer treatment.

Comparison of the prognosis among in-hospital survivors of cardiogenic shock based on etiology: AMI and Non-AMI

BackgroundCurrent data on post-discharge mortality and rehospitalization is still insufficient among in-hospital survivors of cardiogenic shock (CS), including acute myocardial infarction (AMI) and non-AMI survivors.MethodsPatients with CS who survived after hospital discharge were selected from the Taiwan National Health Insurance Research Database. Each patient was followed up at 3-year intervals. Mortality and rehospitalization were analyzed using Kaplan-Meier curves and Cox regression models.ResultsThere were 16,582 eligible patients. Of these, 42.4% and 57.6% were AMI-CS and non-AMI-CS survivors, respectively. The overall mortality and rehospitalization rates were considerably high, with reports of 7.0% and 22.1% at 30 days, 24.5% and 58.2% at 1 year, and 38.9% and 73.0% at 3 years, respectively, among in-hospital CS survivors. Cardiovascular (CV) problems caused approximately 40% mortality and 60% rehospitalization. Overall, the non-AMI-CS group had a higher mortality burden than the AMI-CS group owing to older age and a higher prevalence of comorbidities. In multivariable models, the non-AMI-CS group exhibited a lower risk of all-cause mortality (adjusted hazard ratio [aHR] 0.69, 95% confidence interval [CI] 0.60 to 0.78) and CV mortality (aHR 0.65, 95% CI 0.54 to 0.78) compared to the AMI-CS group. However, these risks diminished and even reversed after one year (aHR 1.13, 95% CI 1.03 to 1.25 for all-cause mortality; aHR 1.27, 95% CI 1.09 to 1.49 for CV mortality).This reversal was not observed in all-cause and CV rehospitalization. For rehospitalization, AMI-CS was associated with the risk of CV rehospitalization in the entire observation period (aHR:0.80, 95% CI:0.76–0.84).ConclusionsIn-hospital AMI-CS survivors had an increased risk of CV rehospitalization and 30-day mortality, whereas those with non-AMI-CS had a greater mortality risk after 1-year follow-up.

Overall survival in patients with acute lymphoblastic leukemia treated with protocol CALGB 9511 at a tertiary hospital in the state of Ceará.

Introduction: Acute lymphoblastic leukemia (ALL) is the most common neoplasm in childhood and has high survival rates. In adults, due to the biological characteristics of the disease and chemotherapy-related toxicity, survival is lower. CALGB 9511 is a chemotherapy protocol based on pediatric regimens with high remission rates after induction. Objectives: To evaluate the survival of patients with ALL undergoing the CALGB 9511 protocol at Walter Cantídio University Hospital (HUWC); to describe the impact of risk factors: presence of measurable residual disease, BCR-ABL fusion gene status, and allogeneic bone marrow transplant (BMT) on the survival of this group. Methodology: Retrospective evaluation of medical records of patients with ALL treated with this protocol between 2011 and 2022. Statistical analysis was performed using the Kaplan-Meier method to estimate survival probability. Results: 79 patients were eligible; 19% were BCR-ABL positive; the mean 2-year overall survival was 44%; The 2-year survival rate for patients undergoing HSCT was approximately 78%.. Conclusion: The survival curves of the study conducted at HUWC are similar to those described in the literature and corroborate the severity of the disease. Accessibility to new therapeutic modalities is a strategy that can improve the survival of these patients.

FLT3-MUTATED ACUTE MYELOID LEUKEMIA OUTCOMES IN A NORTHEAST BRAZILIAN UNIVERSITY HOSPITAL

Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene occur in approximately 25-45% of new diagnoses of Acute myeloid leukemia. The addition of FLT3 inhibitors to conventional protocols improves overall survival in this condition. Objectives: To assess the incidence of FLT3 gene mutation among patients diagnosed with AML at Walter Cantídio University Hospital; Describe access to FLT3 inhibitors and bone marrow transplantation (BMT), and the overall survival of this group. Methodology: Retrospective evaluation of medical records of patients treated for AML between 2020 and 2022. Statistical analysis was performed using the Kaplan-Meier method to estimate survival probability. Results: 47 patients were diagnosed with AML during this period, of whom 17% had FLT3+ mutation. 3/8 patients accessed FLT3 inhibitors. The median survival with FLT3+ mutation was 9.1 months vs. 12.9 months in FLT3- (p = 0.196). The overall survival of AML patients was 30.9% at 2 years. 11/47 patients underwent allogeneic BMT. Conclusion: The addition of targeted therapies and BMT may contribute to reduce mortality in AML. Elderly patients and those not undergoing HSCT have worse outcomes.

A Novel Neutrophil Extracellular Trap Signature Predicts Patient Chemotherapy Resistance and Prognosis in Lung Adenocarcinoma.

Chemoresistance is a key obstacle in the long-term survival of patients with locally and advanced lung adenocarcinoma (LUAD). This study used bioinformatic analysis to reveal the chemoresistance of gene-neutrophil extracellular traps (NETs) associated with LUAD. RNA sequencing data and LUAD expression patterns were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, respectively. The GeneCards database was used to identify NETosis-related genes (NRGs). To identify hub genes with significant and consistent expression, differential analysis was performed using the TCGA-LUAD and GEO datasets. LUAD subtypes were determined based on these hub genes, followed by prognostic analysis. Immunological scoring and infiltration analysis were conducted using NETosis scores (N-scores) derived from the TCGA-LUAD dataset. A clinical prognostic model was established and analyzed, and its clinical applications explored. Twenty-two hub genes were identified, and consensus clustering was used to identify two subgroups based on their expression levels. The Kaplan-Meier (KM) curves demonstrated statistically significant differences in prognosis between the two LUAD subtypes. Based on the median score, patients were further divided into high and low N-score groups, and KM curves showed that the N-scores were more precise at predicting the prognosis of patients with LUAD for overall survival (OS). Immunological infiltration analysis revealed significant differences in the abundances of 10 immune cell infiltrates between the high and low N-score groups. Risk scores indicated significant differences in prognosis between the two extreme score groups. The risk scores for the prognostic model also indicated significant differences between the two groups. The results provide new insights into NETosis-related differentially expressed genes (NRDEGs) associated with chemotherapy resistance in patients with LUAD. The established prognostic model is promising and could help with clinical applications to evaluate patient survival and therapeutic efficiency.

Identification of NINJ1 as a novel prognostic predictor for retroperitoneal liposarcoma

BackgroundRetroperitoneal liposarcoma (RPLS) is known for its propensity for local recurrence and short survival time. We aimed to identify a credible and specific prognostic biomarker for RPLS.MethodsCases from The Cancer Genome Atlas (TCGA) sarcoma dataset were included as the training group. Co-expression modules were constructed using weighted gene co-expression network analysis (WGCNA) to explore associations between modules and survival. Survival analysis of hub genes was performed using the Kaplan–Meier method. In addition, independent external validation was performed on a cohort of 135 Chinese RPLS patients from the REtroperitoneal SArcoma Registry (RESAR) study (NCT03838718).ResultsA total of 19 co-expression modules were constructed based on the expression levels of 26,497 RNAs in the TCGA cohort. Among these modules, the green module exhibited a positive correlation with overall survival (OS, p = 0.10) and disease-free survival (DFS, p = 0.06). Gene set enrichment analysis showed that the green module was associated with endocytosis and soft-tissue sarcomas. Survival analysis demonstrated that NINJ1, a hub gene within the green module, was positively associated with OS (p = 0.019) in the TCGA cohort. Moreover, in the validation cohort, patients with higher NINJ1 expression levels displayed a higher probability of survival for both OS (p = 0.023) and DFS (p = 0.012). Multivariable Cox analysis further confirmed the independent prognostic significance of NINJ1.ConclusionsWe here provide a foundation for the establishment of a consensus prognostic biomarker for RPLS, which should not only facilitate medical treatment but also guide the development of novel targeted drugs.

A novel disulfide death-related genes prognostic signature identifies the role of IPO4 in glioma progression

Background“Disulfide death,” a form of cellular demise, is triggered by the abnormal accumulation of intracellular disulfides under conditions of glucose deprivation. However, its role in the prognosis of glioma remains undetermined. Therefore, the main objective of this study is to establish prognostic signature based on disulfide death-related genes (DDRGs) and to provide new solutions in choosing the effective treatment of glioma.MethodsThe RNA transcriptome, clinical information, and mutation data of glioma samples were sourced from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), while normal samples were obtained from the Genotype-Tissue Expression (GTEx). DDRGs were compiled from previous studies and selected through differential analysis and univariate Cox regression analysis. The molecular subtypes were determined through consensus clustering analysis. Further, LASSO analysis was employed to select characteristic genes, and subsequently, a risk model comprising seven DDRGs was constructed based on multivariable Cox analysis. Kaplan-Meier survival curves were employed to assess survival differences between high and low-risk groups. Additionally, functional analyses (GO, KEGG, GSEA) were conducted to explore the potential biological functions and signaling pathways of genes associated with the model. The study also explored immune checkpoint (ICP) genes, immune cell infiltration levels, and immune stromal scores. Finally, the effect of Importin-4(IPO4) on glioma has been further confirmed through RT-qPCR, Western blot, and cell functional experiments.Results7 genes associated with disulfide death were obtained and two subgroups of patients with different prognosis and clinical characteristics were identified. Risk signature was subsequently developed and proved to serve as an prognostic predictor. Notably, the high-risk group exhibited an immunosuppressive microenvironment characterized by a high concentration of M2 macrophages and regulatory T cells (Tregs). In contrast, the low-risk group showed lower half-maximal inhibitory concentration (IC50) values. Therefore, patients in the high-risk group may benefit more from immunotherapy, while patients in the low-risk group may benefit more from chemotherapy. In addition, in vitro experiments have shown that inhibition of the expression of IPO4 leads to a significant reduction in the proliferation, migration, and invasion of glioma cells.ConclusionThis study identified two glioma subtypes and constructed a prognostic signature based on DDRGs. The signature has the potential to optimize the selection of patients for immune- and chemotherapy and provided a potential therapeutic target for glioma.

Ductal carcinoma in situ and cause-specific mortality among younger and older postmenopausal women: the Women's Health Initiative.

Whether DCIS is associated with higher breast cancer-specific and all-cause mortality is unclear with few studies in older women. Therefore, we examined DCIS and breast cancer-specific, cardiovascular (CVD)-specific, and all-cause mortality among Women's Health Initiative (WHI) Clinical Trial participants overall and by age (< 70 versus ≥ 70 years). Of 68,132 WHI participants, included were 781 postmenopausal women with incident DCIS and 781 matched controls. Serial screening mammography was mandated with high adherence. DCIS cases were confirmed by central medical record review. Adjusted multivariable Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Kaplan Meier (KM) plots were used to assess 10-year and 20-year mortality rates. After 20.3 years total, and 13.2 years median post-diagnosis follow-up, compared to controls, DCIS was associated with higher breast cancer-specific mortality (HR 3.29; CI = 1.32-8.22, P = 0.01). The absolute difference in 20-year breast cancer mortality was 1.2% without DCIS and 3.4% after DCIS, log-rank P = 0.026. Findings were similar by age (< 70 versus ≥ 70 years) with no interaction (P interaction = 0.80). Incident DCIS was not associated with CVD-specific mortality (HR 0.77; CI-0.54-1.09, P = 0.14) or with all-cause mortality (HR 0.96; CI = 0.80-1.16, P = 0.68) with similar findings by age. In postmenopausal women, incident DCIS was associated with over three-fold higher breast cancer-specific mortality, with similar findings in younger and older postmenopausal women. These finding suggest caution in using age to adjust DCIS clinical management or research strategies.

Association Analysis Between Intratumoral and Peritumoral MRI Radiomics Features and Overall Survival of Neoadjuvant Therapy in Rectal Cancer.

The use of peritumoral features to determine the survival time of patients with rectal cancer (RC) is still imprecise. To explore the correlation between intratumoral, peritumoral and combined features, and overall survival (OS). Retrospective. One hundred sixty-six RC patients (53 women, 113 men; average age: 55 ± 12 years) who underwent radical resection after neoadjuvant therapy. 3 T; T2WI sagittal, T1WI axial, T2WI axial with fat suppression, and high-resolution T2WI axial sequences, enhanced T1WI axial and sagittal sequences with fat suppression. Radiologist A segmented 166 patients, and radiologist B randomly segmented 30 patients. Intratumoral and peritumoral features were extracted, and features with good stability (ICC ≥0.75) were retained through intra-observer analysis. Seven classifiers, including Logistic Regression (LR), Support Vector Machine (SVM), K-Nearest Neighbors (KNN), Random Forest (RF), Extremely randomized trees (ET), eXtreme Gradient Boosting (XGBoost), and LightGBM (LGBM), were applied to select the classifier with the best performance. Next, the Rad-score of best classifier and the clinical features were selected to establish the models, thus, nomogram was built to identify the association with 1-, 3-, and 5-year OS. LASSO, regression analysis, ROC, DeLong method, Kaplan-Meier curve. P < 0.05 indicated a significant difference. Only Node (irregular tumor nodules in the surrounding mesentery) and ExtraMRF (lymph nodes outside the perirectal mesentery) were significantly different in 20 clinical features. Twelve intratumoral, 3 peritumoral, and 14 combined features related to OS were selected. LR, SVM, and RF classier showed the best efficacy in the intratumoral, peritumoral, and combined model, respectively. The combined model (AUC = 0.954 and 0.821) had better survival association than the intratumoral model (AUC = 0.833 and 0.813) and the peritumoral model (AUC = 0.824 and 0.687). The proposed peritumoral model with radiomics features may serve as a tool to improve estimated survival time. 3 TECHNICAL EFFICACY: Stage 4.

[Comparison of surgical outcomes between Kahook Dual Blade goniotomy and Trabectome surgery in patients with open-angle glaucoma].

Objective: To compare the medium-term therapeutic effects of Kahook Dual Blade (KDB) goniotomy and Trabectome surgery in the treatment of patients with primary open-angle glaucoma (POAG). Methods: This study was a non-randomized prospective interventional controlled clinical study. POAG patients who underwent KDB goniotomy or Trabectome surgery at Beijing Tongren Hospital from May 2017 to April 2022 were enrolled. The definition of successful surgery was postoperative average intraocular pressure (IOP)≤21 mmHg (1 mmHg=0.133 kPa) and IOP decrease≥20%. Follow-up visits were conducted on the 1st day, 1st week, 1st, 3rd and 6th month after surgery. The IOP value, the number of IOP-lowering medications, the proportion of surgical success (average IOP≤21 mmHg at 6 months), and complications were evaluated. Statistical methods included independent sample t-test, Mann-Whitney rank sum test, χ2 test, repeated measures two-factor analysis of variance, Bonferroni, Friedman M test, Wilcoxon, and Log-rank. The Kaplan-Meier method was used to calculate the cumulative success rate of each group. Results: Seventeen male patients (17 eyes) and 10 female patients (10 eyes) were included. The mean age was (39.9±17.7) years old. There were 11 patients in the KDB group and 16 patients in the Trabectome group. There was no significant difference in clinical baseline conditions between the two groups (P>0.05). The IOPs in the KDB and Trabectome groups at postoperative 1 week [(16.6±6.3) and (16.4±4.1) mmHg) and 6 months [(17.8±5.3) and (19.9±4.4) mmHg) were lower than those before surgery [(25.1±9.3) and (27.4±9.1) mmHg) (all P<0.05). There was no significant difference in the overall IOP between groups (P>0.05). The IOP reduction rates in the KDB and Trabectome groups were 23.4% and 19.0%, with no significant difference (P=0.674). The numbers of IOP-lowering medications used in the KDB and Trabectome groups at 3 months [2.0 (1.0, 4.0) and 2.0 (1.0, 2.3)] and 6 months [2.0 (0.0, 4.0) and 2.0 (1.0, 3.0)] after surgery were not significantly different from those before surgery [4.0 (2.0, 4.0) and 3.0 (2.0, 4.0)] (both P>0.05). There was no statistical significance in the overall number of IOP-lowering medications used between the two groups (P>0.05). There was also no statistically significant difference in the proportion of patients with an IOP decrease of≥20% and the proportion of patients whose mean postoperative IOP was≤21 mmHg (all P>0.05). The proportions of IOP≤21 mmHg in the KDB group and the Trabectome group at 6 months after surgery were 81.8% and 68.8% (P>0.05). Serious intraoperative or postoperative complications occurred in neither group. Conclusions: Both KDB trabeculotomy and Trabectome surgery can effectively reduce IOP and have a good safety profile in treating POAG, with the same number of IOP-lowering medications.

Characterization of alternative splicing events and prognostic signatures in gastric cancer

BackgroundAccumulating evidences indicate that the specific alternative splicing (AS) events are linked to the occurrence and prognosis of gastric cancer (GC). Nevertheless, the impact of AS is still unclear and needed to further elucidation.MethodsThe expression profile of GC and normal samples were downloaded from TCGA. AS events were achieved from SpliceSeq database. Cox regression together with LASSO analysis were employed to identify survival-associated AS events (SASEs) and calculate risk scores. PPI and pathway enrichment analysis were implemented to determine the function and pathways of these genes. Kaplan-Meier (K-M) analysis and Receiver Operating Characteristic Curves were used to evaluate the clinical significance of genes of SASEs. Q-PCR were applied to validate the hub genes on the survival prognosis in 47 GC samples. Drug sensitivity and immune cell infiltration analysis were conducted.ResultsIn total, 48 140 AS events in 10 610 genes from 361 GC and 31 normal samples were analyzed. Through univariate Cox regression, 855 SASEs in 763 genes were screened out. Further, these SASEs were analyzed by PPI and 17 hub genes were identified. Meanwhile, using Lasso and multivariate Cox regression analysis, 135 SASEs in 132 genes related to 7 AS forms were further screened and a GC prognostic model was constructed. K-M curves indicates that high-risk group has poorer prognosis. And the nomogram analysis on the basis of the multivariate Cox analysis was disclosed the interrelationships between 7 AS forms and clinical parameters in the model. Five key genes were then screened out by PPI analysis and Differential Expression Gene analysis based on TCGA and Combined-dataset, namely STAT3, RAD51B, SOCS2, POLE2 and TSR1. The expression levels of AS in STAT3, RAD51B, SOCS2, POLE2 and TSR1 were all significantly correlated with survival by qPCR verification. Nineteen drugs were sensitized to high-risk patients and eight immune cells showed significantly different infiltration between the STAD and normal groups.ConclusionsIn this research, the prognostic model constructed by SASEs can be applied to predict the prognosis of GC patients and the selected key genes are expected to become new biomarkers and therapeutical targets for GC treatment.

FIGO 2023 endometrial staging: a leap of faith into the new “prognostic based’ rather than “anatomical based” staging—too fast too furious??

BackgroundIn 2023 FIGO revised the endometrial cancer staging system after 13 years. There is a lacuna of data regarding the performance and practicality of the revised 2023 FIGO staging schema for endometrial cancer from Low Middle-Income Countries (LMIC).ObjectiveTo estimate the shift of stage and adjuvant management of endometrial cancer based on the FIGO 2023 system compared to the FIGO 2009 system and assess the predictive potential of the FIGO 2023 system.Material and methodsA retrospective study was conducted from 1st January 2017 to 31st December 2022. All patients with endometrial cancer were staged according to the FIGO 2023 and FIGO 2009 staging system. Follow-up of patients was done to determine recurrence.ResultsA total of 152 patients were included. Aggressive histology was seen in 66 (45%) patients. Eighteen (11%) had subserosal involvement. Substantial LVSI was noted in 23 (15%) of patients. Twenty-four (47%) patients of FIGO 2009 Stage IA and 26 patients (63%) of FIGO 2009 Stage IB were upstaged. Eleven (50%) patients of FIGO 2009 Stage IIIA were down staged to IA3. Overall 23 patients (15%) had a shift of stage. Fifteen out of 152 patients (15%) would have had a possible risk stratification change which would imply 23 patients (15%) would have needed a more radical treatment. Molecular classification was done in 32 patients; however, only 2 patients could afford POLE testing. Kaplan–Meier curves showed significant PFS differences in FIGO 2009 Stage IB and Stage IIIA when restaged according to the FIGO 2023 system.ConclusionThe FIGO 2023 endometrial staging is a more robust prognosticator; however, the practicality of molecular classification in LMICs is still a distant dream.