Prognostic Efficacy Research Articles

P0142 CD47-SIRPα Contributes to the Microenvironment of Stricturing Crohn's Disease by Mediating the Crosstalk between Macrophages and Stromal cells: “Eat Me” or “Don't Eat Me”

Abstract Background Intestinal fibrosis is a common complication of Crohn’s disease (CD), but no anti-fibrotic therapy is currently available. Collagen deposition, the pathological characteristics of intestinal fibrosis, is driven by an imbalance between extracellular matrix (ECM) production and degradation, which is controlled by the crosstalk between stromal cells and macrophage phagocytosis. The underlying mechanism of macrophage phagocytosis is the interplay between “eat me” signals and “don’t eat me”, among which CD47-SIRPa is the dominant pair. This study aims to investigate the role and therapeutic potential of CD47-SIRPa in intestinal fibrosis. Methods Thirty CD patients who underwent surgery due to fibrosis-induced intestinal obstruction were included in this study and the intestinal tissues were collected from both fibrotic and normal sites. Col1a2-CreERT2; Cd47 flox mice and Lyz2-Cre; SIRPα flox mice were used to conditionally ablate CD47/SIRPα. Mice intestinal fibrosis was induced by chronic dextrane sodium sulfate (DSS) and anti-CD47/anti-SIRPα antibody was treated intraperitoneally. Human and mice tissues were applied for single-cell RNA sequencing, flow cytometry, pathological evaluation, immunofluorescence staining, qPCR and in vitro experiment. Smart-seq were performed to detect the functional change of mice macrophage. Results Single-cell RNA sequencing and flow cytometry showed the proportion of CD47+ stromal cells and SIRPα+ macrophages significantly increased in intestinal fibrosis (Figure 1A). CD47+ stromal cells were in senescence-associated secretory phenotype (SASP), while macrophages also acquired a pro-fibrotic immature phenotype (all p<0.05). Moreover, we found the elevation of macrophage SIRPα expression was caused by CD47+ stromal cells and they extensively co-located in fibrotic lesions to form a pathogenic niche(Figure 1B). Conditionally ablation of CD47 in stromal cell or SIRPα in macrophage could significantly reduce collagen deposition(Figure 1C). Meanwhile, both anti-CD47 and anti-SIRPα treatment significantly attenuated mice intestinal fibrosis compared to the control.(Figure 1D) Mice intestinal macrophages acquired an anti-fibrotic phenotype and regained the capacity of phagocytosis by upregulating Clec7a and MMP10 after antibody treatment (all p<0.05) (Figure 1E). Furthermore, under the same total treatment dose, initiating antibody intervention at the earliest stage could achieve the best prognostic efficacy, highlighting its potential to be a therapeutic and preventive strategy against intestinal fibrosis (Figure 1F). Conclusion CD47-SIRPa mediated macrophage-stromal cell crosstalk significantly contributed to structuring CD and may be a novel therapeutic target for intestinal fibrosis.

Revolutionizing ESCC prognosis: the efficiency of tumor-infiltrating immune cells (TIIC) signature score

BackgroundPatients suffer from esophageal squamous cell carcinoma (ESCC), which is the ninth highly aggressive malignancy. Tumor-infiltrating immune cells (TIIC) exert as major component of the tumor microenvironment (TME), showing possible prognostic value in ESCC.MethodsTranscriptome data and scRNA-seq data of ESCC samples were extracted from the GEO and TCGA databases. Tissue Specific Index (TSI) was defined to identify potential TIIC-RNAs from the TME. Twenty machine learning algorithms were further applied to evaluate the prognostic efficacy of TIIC signature score. Gene colocalization analysis was performed. Differences in CNV on chromosomes and SNP sites of prognostic model genes were calculated.ResultsThe most reliable model of TIIC signature score was developed based on three prognostic TIIC-RNAs. It showed a higher C-index than any other reported prognostic models. ESCC patients with high TIIC signature score showed poorer survival outcomes than low TIIC signature score. The activity of most immune cells decreased with the increase of TIIC score. TIIC signature score showed difference in the expression levels and methylation levels of DEGs. There was also significant different correlation with the degree of CNV amplification and CNV deletion of the immune checkpoint genes. Gene colocalization analysis showed two prognostic model genes (ATP6V0E1 and BIRC2). MR analysis found that rs148710154 and rs75146099 SNP sites of TIIC-RNA gene had a significant correlation between them gastro-oesophageal reflux and ESCC.ConclusionTIIC signature score was the first time developed which provided a novel strategy and guidance for the prognosis and immunotherapy of ESCC. It also gave the evidence in the important role of immune cells from the TME in the treatment of cancers.

Migrasome-related prognostic signature TSPAN4 correlates with immune infiltrates and metabolic disturbances in hepatocellular carcinoma.

We aim to comprehensively analyze and validate the prognostic efficacy of tetraspanin 4 (TSPAN4) and several other migrasome-related markers in hepatocellular carcinoma (HCC). The expression, diagnostic, and prognostic efficacy of five migrasome-related genes in HCC were analyzed using several databases. Five pairs of adjacent non-tumor tissues and HCC tissues were used to validate the expression. The prognostic efficacy of TSPAN4 was validated in a HCC cohort. TSPAN4 was knocked down in Huh-7 cells, EdU, and CCK-8, and wound healing assays were conducted to analyze its effects on cell proliferation and migration. In addition, transcriptomic sequencing was used to identify differentially expressed genes. Compared with those in normal tissues, four genes (TSPAN4, PIGK, NDST1, and CPQ) were elevated in liver hepatocellular carcinoma (LIHC), but not TSPAN7. Of these, only elevated TSPAN4 predicted unfavorable prognosis of HCC patients. The expression and prognostic efficacy of TSPAN4 were further confirmed in a HCC cohort (97 patients); and patients in the TSPAN4high group showed unfavorable overall survival (log-rank P = 0.0055). Functional analysis showed that TSPAN4 knockdown significantly suppressed cell migration, but not cell proliferation. Moreover, TSPAN4 knockdown induced disturbances of the metabolic pathways, mainly pentose and glucuronate interconversions. TPSAN4 is a promising prognostic and therapeutic target for HCC treatment and may be involved in the metabolic pathways that affect disease progression.

The role of radiomics for predicting of lymph-vascular space invasion in cervical cancer patients based on artificial intelligence: a systematic review and meta-analysis.

The primary aim of this study was to conduct a methodical examination and assessment of the prognostic efficacy exhibited by magnetic resonance imaging (MRI)-derived radiomic models concerning the preoperative prediction of lymph-vascular space infiltration (LVSI) in cervical cancer cases. A comprehensive and thorough exploration of pertinent academic literature was undertaken by two investigators, employing the resources of the Embase, PubMed, Web of Science, and Cochrane Library databases. The scope of this research was bounded by a publication cutoff date of May 15, 2023. The inclusion criteria encompassed studies that utilized radiomic models based on MRI to prognosticate the accuracy of preoperative LVSI estimation in instances of cervical cancer. The Diagnostic Accuracy Studies-2 framework and the Radiomic Quality Score metric were employed. This investigation included nine distinct research studies, enrolling a total of 1,406 patients. The diagnostic performance metrics of MRI-based radiomic models in the prediction of preoperative LVSI among cervical cancer patients were determined as follows: sensitivity of 83% (95% confidence interval [CI]=77%-87%), specificity of 74% (95% CI=69%-79%), and a corresponding AUC of summary receiver operating characteristic measuring 0.86 (95% CI=0.82-0.88). The results of the synthesized meta-analysis did not reveal substantial heterogeneity.This meta-analysis suggests the robust diagnostic proficiency of the MRI-based radiomic model in the prognostication of preoperative LVSI within the cohort of cervical cancer patients. In the future, radiomics holds the potential to emerge as a widely applicable noninvasive modality for the early detection of LVSI in the context of cervical cancer.

IINS Vs CALLY Index: A Battle of Prognostic Value in NSCLC Patients Following Surgery.

This research sought to assess the predictive potential of the inflammation-immunity-nutrition score (IINS) and the high-sensitivity C-reactive protein-albumin-lymphocyte (CALLY) index in individuals with NSCLC post-surgery. The study enrolled 506 patients with NSCLC undergoing R0 resection at the First Affiliated Hospital of Xi'an Jiaotong University. The training cohort was analyzed utilizing X-tile software to identify the ideal threshold values for categorizing high-sensitivity C-reactive protein, albumin, lymphocyte count, and the CALLY index. The predictive significance of the IINS and CALLY index was evaluated through Kaplan-Meier survival curves and univariate and multivariate Cox regression analyses. Predictive capabilities of the IINS and CALLY index were compared utilizing receiver operating characteristic (ROC) curve analysis, time-dependent ROC curve analysis, and decision curve analysis (DCA). Internal validation was performed in the validation cohort and all data from both the training and validation cohorts using Kaplan-Meier curves and DCA. Patients with lower IINS exhibited prolonged overall survival (OS), whereas those with lower CALLY had shorter OS. Multivariate analysis identified N stage, NSE, and IINS as independent prognostic factors for individuals with NSCLC. ROC analysis revealed that IINS provided superior prognostic performance to CALLY and other traditional indicators (CAR, PLR, and NLR). Time-dependent ROC analyses and DCA further confirmed the superior prognostic value of IINS over the CALLY index at 1, 2, and 3 years. This study reveals that both the IINS and CALLY index are effective in forecasting the prognosis of individuals with NSCLC following surgery, with the IINS demonstrating superior prognostic efficacy to the CALLY index.

Interleukin-6 as a Pan-Cancer Prognostic Inflammatory Biomarker: A Population-Based Study and Comprehensive Bioinformatics Analysis.

Interleukin-6 (IL-6) is a central factor linking inflammation to cancer. This study aimed to provide a comprehensive assessment of the prognostic value of IL-6 and its immunotherapeutic features using a population-based pan-cancer analysis and comprehensive bioinformatic analysis. In the cohort study, 540 patients were included to explore the prognostic value of serum IL-6 levels in cancer. The differential expression of IL-6 and its association with survival and immune cell infiltration were investigated using the TCGA database. The SangerBox database was used to analyze the correlation between IL-6 expression and immune checkpoint (ICP), tumor mutation burden (TMB), and microsatellite instability (MSI) in cancer. Genomic changes in the IL-6 levels were studied using the c-BioPortal database. The IL-6 co-expression network was analyzed using the LinkedOmics database. Serum IL-6 is an independent prognostic factor for cancer, especially gastrointestinal cancers. Compared to other serum inflammatory markers, serum IL-6 is an optimal biomarker for cancer prognosis. A comprehensive bioinformatics analysis showed higher IL-6 expression in human cancers than in the paired normal tissues. The IL-6 expression is closely associated with prognosis, ICP, TMB, and MSI. In addition, it is also strongly correlated with tumor-infiltrating cells. IL-6 levels are significantly associated with the prognosis of stomach adenocarcinoma (STAD). The IL-6 co-expression network in STAD is mainly involved in regulating inflammatory pathways and cell communication. IL-6 is a potential prognostic and immune biomarker of cancer. Compared to other clinical inflammatory biomarkers, IL-6 demonstrates superior prognostic efficacy.

KRAS Mutations in Cholangiocarcinoma: Prevalence, Prognostic Value, and KRAS G12/G13 Detection in Cell-Free DNA.

Cholangiocarcinoma (CCA) is an aggressive hepatobiliary malignancy characterized by genomic heterogeneity. KRAS mutations play a significant role in influencing patient prognosis and guiding therapeutic decision-making. This study aimed to determine the prevalence and prognostic significance of KRAS mutations in CCA, asses the detection of KRAS G12/G13 mutations in plasma cell-free DNA (cfDNA), and evaluate the prognostic value of KRAS G12/G13 mutant allele frequency (MAF) in cfDNA in relation to clinicopathological data and patient survival. A retrospective analysis of 937 CCA patients was performed using data from cBioPortal to examine KRAS mutation profiles and their association with survival. Plasma from 101 CCA patients was analyzed for KRAS G12/G13 mutations in the cfDNA using droplet digital PCR, and the results were compared with tissue-based sequencing from 78 matched samples. KRAS driver mutations were found in 15.6% of patients, with common variants being G12D (37.0%), G12V (24.0%) and Q61H (8.2%). Patients harboring KRAS mutations exhibited decreased overall and recurrence-free survival. KRAS G12/G13 mutations were detected in 14.9% of cfDNA samples, showing moderate concordance with tissue sequencing, and achieving 80% sensitivity and 93% specificity. Elevated KRAS G12/G13 MAF in cfDNA, combined with high CA19-9 levels, correlated with poorer survival outcomes. The presence of KRAS mutations was associated with poor survival in CCA, underscoring the importance of KRAS mutations as prognostic markers. The detection of KRAS mutations in cfDNA demonstrated potential as a promising non-invasive alternative for mutation detection and, when combined with CA19-9 levels, may improve prognostic efficacy in CCA.

Serum NLR combined with CA125 and HE4 improves the diagnostic and prognostic efficiency in patients with ovarian cancer.

Ovarian cancer (OC) represents a common neoplasm within the female reproductive tract. The prognosis for patients diagnosed at advanced stages is unfavorable, primarily attributable to the absence of reliable screening markers for early detection. An elevated neutrophil-to-lymphocyte ratio (NLR) serves as an indicator of host inflammatory response and has been linked to poorer overall survival (OS) across various cancer types; however, its examination in OC remains limited. This study seeks to identify combination diagnostic and prognostic markers for OC, aiming to improve diagnostic and prognostic efficacy, especially in the early stages. We analyzed the targeted biomarkers in a cohort of 104 OC patients and 100 controls, which comprised 50 patients with benign ovarian tumors and 50 healthy women, using enzyme-linked immunosorbent assay (ELISA) and complete blood counting (CBC). After validating the biomarker panel, we compared the expression levels of the biomarkers in OC patients with various clinical features to assess their relevance. A biomarker panel was developed and validated with an independent cohort of 70 OC patients and 60 controls, including 30 with benign ovarian tumors and 30 healthy women. We evaluated the diagnostic accuracy using the area under the receiver-operating characteristic (ROC) curve and overall survival analysis was used for prognosis. The results from ELISA and CBC analyses indicated that the NLR was significantly higher in patients with OC. This elevation was especially notable in those with advanced stages of the disease, lymph node metastasis, and ascites. The diagnostic performance of the NLR, when combined with CA125 and HE4, outperformed each marker used individually, especially when compared to the traditional combination of CA125 and HE4. Importantly, we observed similar results in patients with early-stage ovarian cancer and those with low levels of CA125 and HE4. In addition, these results suggest that NLR combined with CA125 and HE4 levels in OC patients have significant prognostic value. The effective combination of serum NLR, CA125, and HE4 significantly enhances diagnostic efficiency in patients with OC. Serum NLR, CA125, and HE4 levels were identified as independent prognostic markers for OC.

The landscape in telomere related gene prognostic signature for survival and medication treatment effectiveness prediction in hepatocellular carcinoma

ObjectiveTelomeres, made of repetitive DNA sequences and shelterin complexes, which were found at the ends of chromosomes and had been extensively studied in cancer research. However, in hepatocellular carcinoma (HCC) was still relatively scarce. In this study, we investigated the correlation between telomerase-related genes (TRGs) and the prognosis and immunotherapy of HCC patients to enhance clinical outcomes.MethodsIn this work, TRGs were gathered using TelNet, while clinical information and gene expression data for HCC patients were retrieved from the Cancer Genome Atlas (TCGA) database. A risk prediction model based on TRGs was created using COX and Lasso regression analyses, with ROC curves used to assess prognostic efficacy. Univariate and multifactorial COX regression analyses were used to determine if the risk model had an independent impact on prognosis. Nomograms were created to enhance clinical usability, and calibration curves were used to assess predictive ability at various time points. The Tumor Immune Dysfunction and Exclusion (TIDE) score was used to analyze differences in immune infiltrating cells between risk groups. The study analyzed the relationship between risk ratings and drug treatment effectiveness using data from the CellMiner database. The hub gene was identified and its relationship to prognostic markers of HCC patients was examined. The expression of hub genes in immune cell subpopulations was also investigated by single-cell data.Results2093 TRGs were identified, with 949 showing significant differences in expression between HCC and paracancerous tissues. Seven risk genes were overexpressed in tumor tissues, leading to lower survival rates in high-risk patients. Risk model could independently predict the prognosis of HCC patients. Analysis of tumor immune infiltrating cells revealed significant differences in cell abundance between risk groups, with notable variations in immune subset enrichment between subgroups. Higher risk scores correlated with increased sensitivity to sorafenib, mitoxantrone, oxaliplatin, gemcitabine, and entinostat, while sensitivity decreased for vincristine, etc. CDCA8 was identified as a key gene in the Protein Interaction Network, while high expression associated with poorer overall survival, tumor proliferation and metastasis. The results of single-cell data analysis suggest that CDCA8 may promote the development of HCC by affecting T lymphocytes.ConclusionThe TRG-based risk model could predict HCC patient prognosis and closely linked to tumor immune environment, which could offer new possibilities for clinical treatment.

The Effect of Systemic Immune-Inflammatory Index (SII) and Prognostic Nutritional Index (PNI) in Early Gastric Cancer.

In recent years, the systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) have been considered potential predictors of survival outcomes in various solid tumors, including gastric cancer. However, there is a notable lack of research focusing on their prognostic implications specifically in the early stage of gastric cancer. This study aims to investigate the prognostic indicators of early gastric cancer (EGC), including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), SII, PNI, and lymph node metastasis (LNM). In this retrospective analysis, we examined 490 patients diagnosed with EGC (pT1Nx). The peripheral blood indices of interest were SII, PNI, PLR, and NLR. The receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to determine optimal cutoff values and prognostic efficacy for each parameter. Additionally, Kaplan-Meier survival curves and multivariate Cox regression models were utilized to delineate independent prognostic factors. The optimal cutoff values for SII and PNI were determined as 613.05 and 42.21, respectively. Patients in the low SII (SII-L) group demonstrated significantly higher 5-year Disease-Free Survival (DFS) and Overall Survival (OS) rates of 94.7% and 96.2%, compared to the high SII (SII-H) group (DFS: 78.7%; OS: 81.9%), with both differences proving statistically significant (P < 0.001, P < 0.001). Similarly, patients in the high PNI (PNI-H) group showed superior 5-year DFS (93.3%) and OS rates (95.1%) versus the low PNI (PNI-L) group (DFS: 71.4%; OS: 74.3%), also demonstrating statistical significance (P < 0.001, P < 0.001). Multivariate analysis identified SII, PNI, and LNM as independent prognostic factors for EGC. A combined analysis of SII, PNI, and LNM yielded a C-index of 0.723 (P = 0.008). SII, PNI, and LNM are effective markers for predicting the survival outcomes of patients undergoing radical gastrectomy for EGC.

Role of plasma suPAR, sTNFR1, and sTNFR2 levels in risk stratification and outcome prediction of complicated acute kidney injury in elderly patients with coronavirus disease 2019

ObjectiveThe aim of this study is to investigate the early prognostic efficacy of plasma soluble urokinase-type plasminogen activator receptor (suPAR), soluble tumor necrosis factor receptor 1 (sTNFR1), and soluble tumor necrosis factor receptor 2 (sTNFR2) in complicated acute kidney injury (AKI) in patients with coronavirus disease 2019 (COVID-19), and to analyze the relevant factors contributing to complicated AKI in these patients. MethodsPatients with COVID-19 hospitalized at the Affiliated Baiyun Hospital of Guizhou Medical University from March 2022 to March 2024 were selected as study participants. A total of 589 patients met the inclusion and exclusion criteria, 68 patients complicated with AKI were classified as AKI group, and the remaining 521 cases were divided into proportion sampling method and randomly selected 200 samples, which were classified as non-AKI group. Additionally, 50 healthy controls were enrolled as the control group. Logistic regression analysis was conducted to identify the relevant factors associated with complicated AKI in patients with COVID-19. Receiver operating characteristic (ROC) curves were plotted to evaluate the prognostic efficacy of plasma suPAR, sTNFR1, and sTNFR2 indicators for complicated AKI in patients with COVID-19. ResultsAmong the patients with COVID-19 in the AKI group, 43 were males (63.20 %), with a median age of 79.00 (interquartile range: 75.00, 83.00) years, while the non-AKI group comprised 83 males (41.50 %), with a median age of 73.00 (interquartile range: 60.00, 80.75) years. Comparison of the sex and age between the two groups indicated that males and elderly patients had increased risks of complicated AKI (P < 0.05). Plasma levels of suPAR, sTNFR1, and sTNFR2 in the AKI group were significantly higher than those in the non-AKI group (P < 0.05). Logistic regression analysis indicated that suPAR and sTNFR2 were independent factors influencing complicated AKI in patients with COVID-19 (P < 0.05). The ROC curve for a single indicator showed that suPAR had the highest prognostic efficacy for complicated AKI, with an area under the curve (AUC) of 0.813, a sensitivity of 79.4 %, and a specificity of 74.0 %. The combined use of suPAR and sTNFR2 for risk assessment yielded the highest AUC of 0.838, with a sensitivity of 66.2 % and a specificity of 87.5 %. The combined risk assessment using all three indicators (suPAR, sTNFR1, and sTNFR2) had an AUC of 0.837, with a sensitivity of 64.7 % and a specificity of 89.0 %. ConclusionElderly patients had increased risks of complicated AKI. Indicators such as suPAR, sTNFR1, and sTNFR2 can assist in assessing the risk in patients with COVID-19 complicated AKI, with suPAR demonstrating the highest prognostic efficacy as a single indicator. The combined detection of suPAR, sTNFR1, and sTNFR2 offers greater prognostic value than using any single indicator.

Prognostic efficacy of lymph node parameters in resected ampullary adenocarcinoma based on long-term follow-up data after adjuvant treatment

BackgroundLymph node (LN) metastasis is an important prognostic factor in the ampulla of Vater (AoV) adenocarcinoma. Various LN parameters have been proposed, but their prognostic efficacy has not been compared in the same population. We aimed to evaluate the prognostic values of LN parameters in AoV adenocarcinoma patients who underwent surgical resection and adjuvant treatment based on the long-term follow-up data.MethodsA total of 86 patients with surgically resected AoV adenocarcinoma followed by adjuvant treatment were analyzed. We evaluated the prognostic values of various LN parameters such as pathologic N stage, number of metastatic regional LN (LNN), LN ratio (LNR), and log odds of positive LNs (LODDS). Each LN parameter was separately analyzed using Cox regression models with the same confounders.ResultsThe median follow-up period was 69.4 months, and the median overall survival (OS) was 114 months. The median number of dissected LNs is 15, with an interquartile range of 8 to 25. In the univariable analyses, all LN parameters showed significant prognostic efficacy for OS, disease-free survival (DFS), and distant metastasis-free survival (DMFS). In the multivariable Cox regression analyses, LNN ≥ 2 was a statistically significant prognostic factor for OS (hazard ratio (HR) 2.10, 95% confidence interval (CI), 1.11–3.97; p = 0.022), DFS (HR 2.51, 95% CI 1.28–4.93; p = 0.007), and DMFS (HR 2.74, 95% CI 1.39–5.41; p = 0.004). LNR showed significant prognostic performance for DFS (HR 2.35, 95% CI 1.23–4.50; p = 0.010), and DMFS (HR 2.26, 95% CI 1.17–4.35; p = 0.015). N stage showed significant prognostic performance in DFS (HR 1.55 for pN1; p = 0.243 and HR 4.31 for pN2; p = 0.003), DMFS (HR 1.46 for pN1; p = 0.323 and 4.59 for pN2; p = 0.002). LODDS and the presence of LN metastasis, did not demonstrate significant prognostic value across survival outcomes.ConclusionsLN parameters showed good long-term predictive performance in AoV adenocarcinoma patients treated with curative resection and adjuvant treatments. Among LN parameters, LNN ≥ 2 showed better prognostic value than others. Further large-scale studies are needed to validate the clinical usefulness of various LN parameters.

Surgical resection following chemoradiotherapy for thoracic SMARCA4-deficient undifferentiated tumor: a report of two cases

BackgroundThoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a high-grade malignant neoplasm with a poor prognosis. Most cases of SMARCA4-UT have extensive chest wall and mediastinum involvement. The efficacy of surgical resection has not been clearly established. Here, we report two surgical cases of SMARCA4-UT with chest wall invasion after chemoradiotherapy.Case presentationThe first patient was a 40-year-old man with back pain. Computed tomography revealed a 6.8 cm mass in contact with the thoracic vertebrae near the intervertebral foramen, which was suspected to involve the third to fifth ribs. The patient was diagnosed with SMARCA4-UT with clinical T3N0M0 stage IIB. The tumor shrank after chemoradiotherapy, and conversion surgery combined with partial vertebrectomy was performed. Histopathological findings revealed 30% residual tumor in the tumor bed. Thirty-six days after surgery, the patient developed multiple liver metastases and peritoneal dissemination. Chemotherapy combined with immune checkpoint inhibitor treatment was performed, resulting in tumor shrinkage. However, peritoneal dissemination recurred within a short interval. The patient died 5 months postoperatively. The second patient was a 74-year-old man with chest pain. Computed tomography revealed a 7.4-cm mass in the left upper lobe with invasion of the third and fourth ribs. The patient was initially diagnosed with non-small cell lung cancer with clinical T4N1M0 stage IIIA. The tumor shrank after induction chemoradiotherapy, and a left upper lobectomy combined with the chest wall resection was performed. Based on histopathological findings, the patient was diagnosed with SMARCA4-UT. The residual tumor percentage was 3%. The patient was followed up for 12 months postoperatively without recurrence.ConclusionsWe performed the complete resection of SMARCA4-UT following chemoradiotherapy. The two surgical cases had different postoperative courses. Radical surgery after chemoradiotherapy is effective for local control. However, its long-term prognostic efficacy remains unclear. Multidisciplinary approaches and further investigations of novel therapeutic options are required.

Plasma COL10A1 Level, a Potential Diagnostic and Prognostic Biomarker for Pancreatic Ductal Adenocarcinoma.

COL10A1 expression was up-regulated and could promote tumor development in pancreatic cancer. As a secreted protein, plasma COL10A1 level was proven to have certain diagnostic efficacy in gastric cancer, breast cancer, and colorectal cancer. It is still unknown whether it has a biomarker role for pancreatic cancer. To explore and analyze the diagnostic and prognostic value of plasma COL10A1 level in pancreatic ductal adenocarcinoma (PDAC). The RNA-seq dataset of PDAC from The Cancer Genome Atlas (TCGA) and six expression profiling microarray datasets from Gene Expression Omnibus (GEO) were downloaded to analyze the expression of COL10A1 in tissues. Thirty-six patients with PDAC and eighteen healthy volunteers were enrolled to measure COL10A1 levels in tissues and plasmas, and the relationship between clinical characteristics and the COL10A1 levels was analyzed. The diagnostic and prognostic efficacy of plasma COL10A1 levels were calculated. Aspects of COL10A1 expression level in tissues, COL10A1 expression was significantly higher in PDAC tissue than adjacent normal tissue. The expression of COL10A1 was correlated with T, M, and AJCC stages. Patients with high COL10A1 expression had worse recurrence-free survival (RFS) and overall survival (OS) than those with low expression. Aspects of COL10A1 expression levels in plasma, its diagnostic area under the curve (AUC) for PDAC was 0.926 (95% CI 0.853-0.999), diagnostic sensitivity was 81% (95% CI 64-92%), and specificity was 100% (95% CI 81-100%). The time-dependent AUCs at 1-year and 3-year were 0.71 (95% CI 0.51-0.90) and 0.74 (95% CI 0.48-1.00), respectively. In PDAC, plasma COL10A1 levels showed certain diagnostic and prognostic efficacy. COL10A1 may be a diagnostic and prognostic biomarker for PDAC and play a role in liquid biopsy of this disease.

Predictive Prognostic Model for Hepatocellular Carcinoma Based on Seven Genes Participating in Arachidonic Acid Metabolism.

The occult onset and rapid progression of hepatocellular carcinoma (HCC) lead to an unsatisfactory overall survival (OS) rate. Established prognostic predictive models based on tumor-node-metastasis staging and predictive factors do not report satisfactory predictive efficacy. Arachidonic acid plays pivotal roles in biological processes including inflammation, regeneration, immune modulation, and tumorigenesis. We, therefore, constructed a prognostic predictive model based on seven genes linked to arachidonic acid metabolism, using samples of HCC patients from databases to analyze the genomic profiles. We also assessed the predictive stability of the constructed model. Sample data of 365 patients diagnosed with HCC were extracted from The Cancer Genome Atlas (TCGA, training set) and HCCDB18, GSE14520, and GSE76427 databases (validation sets). Patient samples were clustered using ConsensusClusterPlus analysis based on the expression levels of 12 genes involved in arachidonic acid metabolism that were significantly associated with HCC prognosis. Differentially expressed genes (DEGs) within different clusters were distinguished and compared using WebGestaltR. Immunohistochemistry (IHC) analysis was performed using a human HCC tissue microarray (TMA). Tumor immune microenvironment assessment was performed using ESTIMATE, ssGSEA, and TIDE. Samples of patients with HCC were classified into three clusters, with significant differences in OS. Cluster 2 showed the best prognosis, whereas cluster 1 presented the worst. The three clusters showed significant differences in immune infiltration. We then performed Cox and LASSO regression analyses, which revealed CYP2C9, G6PD, CDC20, SPP1, PON1, TRNP1, and ADH4 as prognosis-related hub genes, making it a simplified prognostic model. TMA analysis for the seven target genes showed similar results of regression analyses. The high-risk group showed a significantly worse prognosis and reduced immunotherapy efficacy. Our model showed stable prognostic predictive efficacy. This seven-gene-based model showed stable outcomes in predicting HCC prognosis as well as responses to immunotherapy.

Cancer cell-extrinsic STING shapes immune-active microenvironment and predicts clinical outcome in gastric cancer.

The activation of cGAS-STING pathway can be triggered by cytosolic double-stranded DNA (dsDNA) in tumor and non-tumor compartments. We aim to assess the constitutive expression of dsDNA-cGAS-STING axis in different cellular contexts and compare their relative contribution to clinical outcomes. A cohort of 154 cases of patients with newly diagnosed gastric cancer were enrolled in this study to evaluate the histo-score of cytosolic dsDNA, cGAS, and STING via immunohistochemistry as well as the types and densities of tumor-infiltrating immune cells. Kaplan-Meier method, multivariable regression, and receiver operating characteristic curve were implemented to analyze the prognostic efficacy of dsDNA-cGAS-STING axis in distinct compartments. The supra-normal concentration of cytosolic dsDNA correlated with the constitutive expression of cGAS-STING pathway in tumor compartments. In contrast to the lack of STING within cancer cells, the higher STING expression in non-tumor compartments indicated a transcellular cGAS-STING activation. Cancer cell-extrinsic STING was supported to potentiate nucleic acid immunity by sensing tumor-derived dsDNA fragments. Compartmental analyses also confirmed that the level of STING expressed in non-tumor cells was associated with the infiltration of protective immune cells, leading to the prolonged overall survival. Multivariate analysis further identified the independent prognostic value of cancer cell-extrinsic STING and its predictive accuracy could be significantly improved in combination with the immune cell infiltration. Cancer cell-extrinsic STING facilitates the remodeling of immune-active tumor microenvironment and acts as an independent prognostic factor in gastric cancer.

Necroptosis-based glioblastoma prognostic subtypes: implications for TME remodeling and therapy response

Background Glioblastoma (GBM) is an aggressive primary brain tumor with a high recurrence rate and poor prognosis. Necroptosis, a pathological hallmark of GBM, is poorly understood in terms of its role in prognosis, tumor microenvironment (TME) alteration, and immunotherapy. Methods & Results We assessed the expression of 55 necroptosis-related genes in GBM and normal brain tissues. We identified necroptosis-stratified clusters using Uni-Cox and Least Absolute Shrinkage and Selection Operator (LASSO) regression to establish the 10-gene Glioblastoma Necroptosis Index (GNI). GNI demonstrated significant prognostic efficacy in the TCGA dataset (n = 160) and internal validation dataset (n = 345) and in external validation cohorts (n = 591). The GNI-high subgroup displayed a mesenchymal phenotype, lacking the IDH1 mutation, and MGMT methylation. This subgroup was characterized by significant enrichment in inflammatory and humoral immune pathways with prominent cell adhesion molecules (CD44 and ICAM1), inflammatory cytokines (TGFB1, IL1B, and IL10), and chemokines (CX3CL1, CXCL9, and CCL5). The TME in this subgroup showed elevated infiltration of M0 macrophages, neutrophils, mast cells, and regulatory T cells. GNI-related genes appeared to limit macrophage polarization, as confirmed by immunohistochemistry and flow cytometry. The top 30% high-risk score subset exhibited increased CD8 T cell infiltration and enhanced cytolytic activity. GNI showed promise in predicting responses to immunotherapy and targeted treatment. Conclusions Our study highlights the role of necroptosis-related genes in glioblastoma (GBM) and their effects on the tumor microenvironment and patient prognosis. TheGNI demonstrates potential as a prognostic marker and provides insights into immune characteristics and treatment responsiveness.

The LIVERAID (LIVER And Infectious Diseases)-ICU score predicts in-hospital mortality in liver cirrhosis patients with infections in the intensive care unit

ObjectivesThe admission of patients with liver cirrhosis to the intensive care unit (ICU) due to infections is a frequent occurrence, often leading to complications such as hepatic encephalopathy, renal failure...

Novel multifactor predictive model for postoperative survival in gallbladder cancer: a multi-center study

BackgroundGallbladder cancer (GBC) is a highly aggressive malignancy, with limited survival profiles after curative surgeries. This study aimed to develop a practical model for predicting the postoperative overall survival (OS) in GBC patients.MethodsPatients from three hospitals were included. Two centers (N = 102 and 100) were adopted for model development and internal validation, and the third center (N = 85) was used for external testing. Univariate and stepwise multivariate Cox regression were used for feature selection. A nomogram for 1-, 3-, and 5-year postoperative survival rates was constructed accordingly. Performance assessment included Harrell's concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves. Kaplan-Meier curves were utilized to evaluate the risk stratification results of the nomogram. Decision curves were used to reflect the net benefit.ResultsEight factors, TNM stage, age-adjusted Charlson Comorbidity Index (aCCI), body mass index (BMI), R0 resection, blood platelet count, and serum levels of albumin, CA125, CA199 were incorporated in the nomogram. The time-dependent C-index consistently exceeded 0.70 from 6 months to 5 years, and time-dependent ROC revealed an area under the curve (AUC) of over 75% for 1-, 3-, and 5-year survival. The calibration curves, Kaplan-Meier curves and decision curves also indicated good prognostic performance and clinical benefit, surpassing traditional indicators TNM staging and CA199 levels. The reliability of results was further proved in the independent external testing set.ConclusionsThe novel nomogram exhibited good prognostic efficacy and robust generalizability in GBC patients, which might be a promising tool for aiding clinical decision-making.

Evaluation of prognostic efficacy of liver immune status index in predicting postoperative outcomes in hepatocellular carcinoma patients: A multi-institutional retrospective study.

Hepatocellular carcinoma (HCC) ranks third in cancer-related deaths globally. Despite treatment advances, high post-hepatectomy recurrence rates (RR), especially with liver fibrosis and hepatitis C virus infection, remain challenging. Key prognostic factors include vascular invasion and perioperative blood loss, impacting extrahepatic recurrence. Natural killer (NK) cells are crucial in countering circulating tumor cells through TRAIL-mediated pathways. The aim of this study was to validate the liver immune status index (LISI) as a predictive tool for liver NK cell antitumor efficiency, particularly in HCC patients with vascular invasion. A retrospective analysis of 1337 primary HCC hepatectomies was conducted by the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO). Clinicodemographic data were extracted from electronic medical records. Prognostic indices (FIB-4, ALBI, ALICE, GNRI, APRI, and LISI) were evaluated using area under the receiver operating characteristic curve values. Survival analyses employed Kaplan-Meier estimations and log-rank tests. LISI significantly correlated with other prognostic markers and stratified patients into risk groups with distinct overall survival (OS) and RR. It showed superior predictive performance for 2-year OS and RR, especially in patients with vascular invasion. Over longer periods, APRI and FIB-4 index reliabilities improved. The HISCO-HCC score, combining LISI, tumor burden score, and alpha-fetoprotein levels, enhanced prognostic accuracy. LISI outperformed existing models, particularly in HCC with vascular invasion. The HISCO-HCC score offers improved prognostic precision, guiding immunotherapeutic strategies and individualized patient care in HCC.