Cox Regression Analysis Research Articles

Prognostic value of serum complement cleavage factor Bb in idiopathic membranous nephropathy and establishment of nomogram model

Complement activation is involved in idiopathic membranous nephropathy (IMN). We aimed to investigate the relationship of serum complement cleavage factor Bb with IMN progression, and to establish a model for early prediction of kidney outcomes. We measured serum factor Bb in a retrospective cohort of 449 IMN patients at the time of kidney biopsy. Cox regression analysis showed that higher levels of serum factor Bb were independently associated with IMN progression event defined as end-stage renal disease or ≥ 40% decline in estimated glomerular filtration rate. Patients in the middle and highest tertiles of serum factor Bb had respectively 2.1-, and 2.6-fold higher risk for disease progression compared with those in the lowest tertile. We developed an optimized prognostic nomogram model incorporating age, log serum anti-PLA2R antibody, log serum Bb, proteinuria and tubular atrophy/interstitial fibrosis. The model demonstrated good predictive ability with a concordance index of 0.77 (bootstrap-corrected of 0.76) for predicting 3-, and 5-year kidney survival. Calibration curves and decision curve analysis confirmed the model’s good calibration and clinical utility. Our findings suggest that serum factor Bb may serve as an essential prognostic indicator of IMN. The novel nomogram model may offer important guidance on the management of this patient population.

Mean platelet volume/platelet count ratio can predict the recurrence-free survival rate of patients after complete resection of gastrointestinal stromal tumors

PurposeThe aim of this study is to compare mean platelet volume/platelet count ratio (PVPR) and other indicators’ predictive abilities. Simultaneously, a new nomogram for predicting recurrence-free survival (RFS) after gastrointestinal stromal tumors (GISTs) R0 resection was developed.MethodsFrom January 2010 to July 2019, 295 patients with GIST who were operated on at Harbin Medical University Cancer Hospital were retrospectively reviewed. With a 4-year RFS as the end point, using the Kaplan–Meier methods and log rank test, and then conducting Cox regression analysis, we compared and identified meaningful indicators for predicting prognosis. Finally, a nomogram was developed and validated using calibration curves.ResultsThe receiver operating characteristic curve indicated that a cutoff point of 0.044 was the ideal threshold for PVPR, and patients were divided into a high-PVPR group (≤0.044) and a low-PVPR group (>0.044). Kaplan–Meier curves suggested that PVPR>0.044 had obvious associations with better RFS (p < 0.001). In accordance with multivariate analysis, PVPR (>0.044 vs. ≤0.044) (p = 0.005), National Institutes of Health (NIH) risk category (p < 0.001), and Ki-67 (p = 0.005) were the independent prognostic indicators of RFS. Tumor size, gastrointestinal bleeding, mitotic index, NIH risk category, CD34, and Ki-67 all exhibited an obvious correlation with PVPR (all p < 0.05). The nomogram’s probability of concordance was 0.823, indicating that the nomogram predictions were well calibrated.ConclusionIn GISTs, RFS can be independently predicted by PVPR. Patients with higher PVPR have better RFS. The nomogram including PVPR could be used to assist clinical treatment decision-making.

Pressure Injuries and the Waterlow Subscales in the Intensive Care Unit: A Multicentre Study

ABSTRACTBackgroundPressure injuries (PIs) impose a significant burden on patients in the intensive care unit (ICU) and the healthcare system. Assessing the risk of developing PIs is crucial for prevention. However, it is unclear whether all subscales of the Waterlow scale can be used to assess PIs risk in ICU.ObjectivesTo assess whether all subscales of the Waterlow scale can predict PIs risk in ICU.DesignMulticentre prospective study.MethodsA total of 18,503 patients from ICUs in 40 tertiary‐level hospitals in Gansu province of China were enrolled from April 2021 to August 2023. The incidence and characteristics of PIs were recorded. Univariate Cox regression analyses were performed for each subscale as a predictor of PIs development, followed by multivariate Cox regression with covariates for each subscale separately.ResultsOut of 17,720 patients included, the incidence of PIs was 1.1%. Multivariate analysis revealed skin type (HR: 1.468, 95% CI: 1.229, 1.758), sex (HR: 0.655, 95% CI: 0.472, 0.908), advanced age (HR: 1.263, 95% CI: 1.106, 1.442), continence (HR: 1.245, 95% CI: 1.052, 1.473), tissue malnutrition (HR: 1.070, 95% CI: 1.007, 1.136) and neurological deficit (HR: 1.153, 95% CI: 1.062, 1.251) were independently predictive of PIs development for all participants. Skin type (HR: 2.326, 95% CI: 1.153, 3.010) (HR: 2.217, 95% CI: 1.804, 2.573) independently predicted PIs occurrence for high‐risk and very high‐risk group, respectively, while sex (HR: 0.634, 95% CI: 0.431, 0.931) and age (HR: 1.269, 95% CI: 1.083, 1.487) predicted PIs development for very high‐risk group.ConclusionsThis study found that not all subscales of the Waterlow scale are associated with the PIs development in patients in ICU, highlighting the importance of the skin type subscale in predicting PI risk across all patient groups.Implications for Clinical PracticeNurses need to focus on patient's skin and related (moisture, pain and pressure) conditions and take measures to promote skin health and avoid the occurrence of PI.Patient or Public ContributionNone.

Comprehensive analysis of GPN1 in human cancer and its effects on the migration of hepatocellular carcinoma cells

To investigate the prognostic value of GPN1 in cancer and its role in the migration of hepatocellular carcinoma (HCC or LIHC) cells, we used several databases to assess GPN1 expression levels and effects in human tumors. Furthermore, experiments were conducted to verify changes in GPN1 expression in HCC cell lines and explore its biological function. We found that GPN1 gene and protein expression were significantly increased in several tumor tissues. Higher GPN1 expression was associated with unfavorable overall survival. Additionally, there was a strong association between GPN1 expression and several clinicopathological features, according to multivariate Cox regression analysis. Moreover, GPN1 gene mutation and methylation were present in some tumors. A relationship was also found between GPN1 expression and immune infiltration. Notably, immune checkpoint analysis showed that GPN1 expression was correlated with PD-1/PDL-1 and CTLA-4, suggesting it may serve as a biomarker for predicting immune subtypes and response to immunotherapy in HCC. Enrichment analysis in HCC indicated that GPN1 is primarily involved in RNA metabolism. Additionally, drug sensitivity analysis revealed that GPN1 appeared to be responsive to 16 drugs. Finally, GPN1 upregulation was confirmed to promote the migration of HCC cells. This study provides a comprehensive overview of GPN1 in human cancer and demonstrates that GPN1 contributes to the migration of HCC cells, potentially serving as a prognostic and immunotherapy biomarker.

Health-related quality of life and survival of older adults in Campinas, São Paulo, Brazil: A retrospective analysis from 2008 to 2018

As the average life expectancy continues to rise, the prevalence of multimorbidity is also expected to increase, potentially leading to outcomes such as functional decline, a higher risk of premature death, and adverse effects on overall health and well-being. This study aimed to estimate the survival rates of older adults with varying levels of health-related quality of life (HRQoL) and to assess the association between the domains and components of the 36-item Short Form Health Survey and all-cause mortality over a 10-year period in Brazil. We conducted a retrospective longitudinal study using baseline data from 1,520 elders (aged 60 years and older) who participated in the Health Care Survey of the Municipality of Campinas, São Paulo, Brazil (ISACamp 2008/2009). A linkage was established between the ISACamp databases and the Mortality Information System. An active search was performed for individuals whose data could not be paired to confirm the death status. Survival functions were calculated using the Kaplan–Meier method, while hazard ratios (with 95% confidence intervals) were determined using Cox regression analysis. All HRQoL domains showed proportional hazards and statistically significant differences (p < 0.05) between survival curves, except for the bodily pain domain. In the multivariate analysis, lower scores in physical functioning and role-physical were associated with a 74% and 42% increased risk of death, respectively. In addition, impairments in role-emotional, mental health, and general health heightened the risk of mortality by approximately 36%. Notably, the lowest score in the physical component emerged as a significant predictor of mortality, increasing the probability of death by 47%, while the mental component showed no significant association. Our findings provide compelling evidence of the predictive capacity of HRQoL in evaluating mortality risk among older people in low- and middle-income countries.

Evaluating the Diagnosis of Malnutrition Based on Global Leadership Initiative on Malnutrition (GLIM) Criteria in Community-Dwelling Older Adults (Singapore Longitudinal Aging Study)

Background: A minority of studies using the GLIM criteria for malnutrition diagnosis have performed formal empirical validation. Objectives: To evaluate the concurrent and predictive validity of GLIM criteria with and without prior screening among community-dwelling older adults in Singapore. Method: In the Singapore Longitudinal Aging Study (SLAS-2, n = 2477), malnutrition was diagnosed using single-step and two-step GLIM procedures using the Mini Nutritional Assessment Short Form (MNA-SF) and Elderly Nutritional Index for Geriatric Malnutrition Assessment (ENIGMA) for initial screening. Criterion validity was evaluated using MNA-Full Form (MNA-FF) as reference malnutrition diagnosis. Prognostic validity was evaluated using logistic and Cox regression analyses with respect to impaired quality of life (QoL) and 10-year mortality. Results: GLIM malnutrition with and without MNA-SF or ENIGMA screening showed significant associations with known clinical correlates; single-step GLIM malnutrition: sensitivity = 80%, specificity = 83%; two-step MNA-SF-GLIM malnutrition: sensitivity = 80%, specificity = 85%; two-step ENIGMA-GLIM malnutrition: sensitivity = 74%, specificity = 88%; positive predictive values of around 20% and negative predictive values above 98%. Cohen’s kappa values of agreement were uniformly low (0.26 to 0.32). All showed significant associations with about 50% increased odds of impaired QoL and 10-year mortality, adjusted for age, sex, ethnicity, education levels, and housing type, with the ENIGMA-GLIM malnutrition showing the highest risk estimates. Compared to MNA-FF malnutrition prevalence of 4.1%, GLIM-based malnutrition increased prevalence (14.6% to 19.7%) estimates. Conclusions: The GLIM criteria showed good construct and criterion validity. It increased the number of individuals diagnosed with malnutrition. The agreement between diagnoses of malnutrition was low. Diagnostic and prognostic accuracy vary with the screening instrument used. Early identification of malnutrition using appropriate tools can provide opportunities to delay or prevent the risk of important adverse outcomes such as impaired QoL and mortality.

Is Adjuvant Therapy Necessary for Stage IB Gastric Cancer: A Retrospective Cohort Study.

The benefit of adjuvant therapy for patients with IB gastric cancer (GC) is a topic of debate. This study aimed to evaluate the benefit of adjuvant therapy for patients with IB GC. Overall, the study selected 510 IB GC patients after gastrectomy at the First Medical Center of the Chinese PLA General Hospital, Beijing, China between 2005 and 2018. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method and the log-rank test. Cox regression analyses were used to confirm the independent prognostic factors. Patients who received postoperative adjuvant therapy had a longer 5-year OS (92.9 %) than those who received surgery alone (86.7 %; P < 0.05), but the 5-year DFS did not differ significantly between the two groups (92.6 vs. 95.0 %; P > 0.05). Moreover, DFS did not differ between monotherapy, and combination therapy. Uni- and multivariate analyses showed that older age was a significant risk factor for tumor recurrence. Subgroup analyses also failed to identify suitable candidates for chemotherapy. Because adjuvant therapy did not demonstrate any benefits in terms of tumor recurrence or DFS, these treatment strategies may be unnecessary for IB GC patients after gastrectomy. Further studies are required to identify subgroups of IB GC patients who may benefit from adjuvant treatments.

Sex-Specific Impact of Serum Calcium Levels on Acute Coronary Syndrome Risk: A 19-Year Cohort Study in Korea.

Background: This study aims to investigate the association between serum calcium levels and acute coronary syndrome (ACS) risk, examining whether this relationship differs by sex, given the known differences in calcium metabolism and hormonal influences between males and females. Methods: Utilizing the Korean Genome Epidemiology Study (KoGES) prospective cohort data, our primary exposure variables were serum calcium level and sex. The incidence of ACS served as the main outcome of interest. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression analysis. An interaction analysis was conducted to assess the interaction effect of calcium level and sex on ACS incidence. Results: After adjusting for confounding variables, high calcium intake did not significantly increase ACS incidence, with a hazard ratio (HR) of 1.07 (95% CI: 0.90-1.26). There was also no significant difference in ACS risk between females and males (HR: 0.81, 95% CI: 0.61-1.04). However, interaction effect analysis revealed that higher calcium levels were associated with an increased risk of ACS only in females (HR: 1.24, 95% CI: 1.07-1.58), whereas the association in males was not statistically significant (HR: 0.90, 95% CI: 0.71-1.15). Conclusion: Our study results indicate that elevated serum calcium levels alone did not independently increase the risk of ACS; however, high serum calcium levels were associated with an increased risk of ACS in females but not in males, underscoring the importance of sex-specific factors in assessing and managing ACS risk and highlighting the necessity for personalized medical approaches to improve cardiovascular health outcomes for women.

The prognostic significance of stress hyperglycemia ratio for all-cause and cardiovascular mortality in metabolic syndrome patients: prospective cohort study.

The stress hyperglycemia ratio (SHR) is a new biomarker indicating acute hyperglycemia and predicting adverse outcomes in different conditions. Yet, its impact on metabolic syndrome (MetS) has not been studied. We explored the link between SHR and long-term all-cause and cardiovascular disease (CVD) mortality in MetS patients. We conducted a large prospective cohort study involving 9438 participants diagnosed with MetS, drawn from the 1999-2018 NHANES. MetS diagnosis was based on NCEP-ATPIII criteria. Participants were categorized into three groups based on SHR tertiles: T1 (SHR ≤ 0.890), T2 (SHR 0.890-0.992), and T3 (SHR ≥ 0.992). Cox regression and Kaplan-Meier curve analyses assessed the correlation between SHR and mortalities. Non-linear correlations were explored using restricted cubic splines, and stratification analysis was performed. Out of 9438 MetS patients, 1929 deaths occurred during an average follow-up of 107 ± 64 months, including 541 CVD deaths. All-cause and CVD mortality rates were significantly higher with elevated SHR values (T3) than lower tertiles (23.4% vs. 19.5% and 18.3%, P < 0.001; 6.8% vs. 5.3% and 5.1%, P = 0.007, respectively). A U-shaped relationship was observed between SHR and all-cause and CVD mortality (all P for non-linear < 0.001). Kaplan-Meier analysis indicated higher SHR values associated with increased risk of all-cause and CVD mortality (all log-rank P < 0.001). After adjusting for confounders, multivariate Cox regression showed SHR remained associated with a 1.256-fold and 1.023-fold risk of all-cause and CVD mortality. SHR independently correlates with all-cause and CVD mortality in MetS patients, displaying a U-shaped relationship with clinical endpoints.

Recurrent Hospitalizations for Fluid Overload in Diabetes with Kidney Failure Treated with Dialysis.

Background &amp; Aims Diabetes Mellitus is the most common cause of end-stage kidney disease (ESKD) in Singapore. ESKD patients have high disease burden and are at increased risk of recurrent hospitalizations, including fluid overload. This study aimed to characterize the risk factors associated with readmissions for fluid overload that will identify high-risk hospitalizations for interventions to reduce readmissions. Methods Retrospective cohort study of all hospitalizations for fluid overload in adults with diabetes and ESKD on dialysis in SingHealth hospitals between 2018 and 2021. Fluid overload was defined by discharge codes for fluid overload, heart failure, pulmonary edema, and generalized edema until 30th December 2022. Multivariable Cox regression analysis using the Prentice, Williams and Peterson Total Time (PWP-TT) model was performed for the outcomes of readmissions for fluid overload within 30 days and 90 days of discharge. Results Among 3234 hospitalizations for fluid overload, readmission for fluid overload within 30-day and 90-day occurred in 585 (18.1%) and 967 (29.9%) hospitalizations, respectively. Ischemic heart disease, peripheral vascular disease and lower hemoglobin level were independently associated with readmissions for fluid overload within 30 and 90 days. Additionally, heart failure, hemodialysis (compared to peritoneal dialysis) and lack of statin at discharge were associated with increased 90-day readmission risk. Conclusion Modifiable (hemoglobin level, statin use) and non-modifiable factors (ischemic heart disease, peripheral vascular disease and heart failure) influenced the risk of readmission for fluid overload. These results may guide risk stratification and inform targeted interventions to reduce avoidable, unplanned readmissions for recurrent fluid overload among individuals with diabetes and ESKD.

The association of preoperative serum free fatty acid levels with survival in breast cancer patients

Background and objectivesSerum free fatty acids (FFA) are associated with various types of cancer. However, the prognostic value of preoperative serum FFA levels and breast cancer (BC) remains unclear. This study aimed to elucidate the specific relationship between FFA levels and BC outcomes.MethodsA retrospective review was conducted on 4133 patients with BC admitted to Sun Yat-sen Memorial Hospital from January 2015 to October 2021. Preoperative serum FFA levels were detected by the enzymatic endpoint method. The relationship between serum FFA levels and clinical characteristics was analyzed based on FFA interquartile range. Restricted cubic splines and multivariate Cox regression analyses were used to assess the relationship between preoperative serum FFA levels and overall survival (OS) in patients with BC. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated.ResultsAccording to the FFA interquartile range, FFA levels were significantly correlated with OS (years) (p < 0.001). Restricted cubic spline analysis might reveal a U-shaped relationship between preoperative serum FFA levels and OS, after adjusting for other variables. According to the cutoff points for FFAs, multivariate Cox regression analyses showed that patients with low FFA levels (≤ 250 µmol/L) had higher rates of all-cause mortality and cancer-specific mortality than those with high FFA levels (530–700 µmol/L) in the total population and patients with a BMI of 18.5–24.0 kg/m2. A trend was observed indicating that elevated FFA levels (≥ 715 µmol/L) were associated with worse prognosis; however, this association failed to reach statistical significance.ConclusionsThere might be a nonlinear U-shaped relationship between preoperative serum FFA levels and survival in breast cancer patients, with lower FFA levels associated with worse OS. The effect of elevated FFA levels on prognosis requires further investigation.

Development of a nomogram for predicting pancreatic portal hypertension in patients with acute pancreatitis: a retrospective study

IntroductionPancreatic portal hypertension (PPH) is a rare complication of acute pancreatitis (AP) that can lead to severe gastrointestinal bleeding. The risk factors associated with PPH, as well as the overall...

Individualised prediction of chemotherapy benefit in early-onset colorectal cancer

PurposesWhether patients with early-onset colorectal cancer (EOCRC) receive chemotherapy has been controversial, so our study aimed to screen patients with EOCRC who benefit from chemotherapy.MethodsA total of 2166 EOCRC patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were divided into chemotherapy and non-chemotherapy groups, propensity score matching (PSM) was performed to balance the differences between the groups, and the Kaplan–Meier method was used to calculate the cancer-specific survival (CSS) of EOCRC patients. Multifactorial COX regression analysis was used to identify independent prognostic factors for CSS and to construct a nomogram for predicting CSS in EOCRC patients. The overall risk score was calculated based on Nomogram, and EOCRC patients were classified into high-risk and low-risk groups to assess further chemotherapy's therapeutic effect on patients with different risk stratification.ResultsBefore PSM, patients in the chemotherapy group had poorer CSS (p < 0.001). After PSM, there was no significant difference in patient CSS between the two groups (p = 0.057). Independent prognostic factors (Race, Grade, Pathology, AJCC.N, AJCC.M, CEA, Marital. Status) were screened according to multifactorial COX regression analyses and included in the Nomogram predicting CSS in EOCRC patients. A risk stratification system for EOCRC patients was further developed, and the results showed that chemotherapy had no significant effect on CSS in the low-risk group of patients, but in the high-risk group, chemotherapy significantly improved CSS in EOCRC patients.ConclusionsWe developed a clinical risk model by combining different risk factors, which can accurately screen those with high-risk EOCRC for benefit from chemotherapy. For low-risk EOCRC patients, our results did not observe a better survival benefit from chemotherapy, and more prospective studies are needed in the future to prove our conclusions.

Assessing the validity of METS-IR for predicting the future onset of diabetes: an analysis using time-dependent receiver operating characteristics

BackgroundThe Metabolic Insulin Resistance Score (METS-IR) is a non-invasive proxy for insulin resistance (IR) that has been newly developed in recent years and has been shown to be associated with diabetes risk. Our aim was to assess the predictive value of METS-IR for the future development of diabetes and its temporal differences in people of different sex, age, and body mass index (BMI).MethodsThe current study included 15,453 baseline non-diabetic subjects in the NAGALA cohort and then grouped according to the World Health Organization’s (WHO) recommended criteria for age and BMI. Multivariate Cox regression and time-dependent receiver operator characteristics (ROC) curves were used to analyze the value of METS-IR in assessing and predicting the risk of diabetes in people of different sexes, ages, and BMIs.Results373 individuals developed diabetes during the observation period. By multivariate COX regression analysis, the development of future diabetes was significantly associated with increased METS-IR, and this positive association was stronger in women than in men and in individuals < 45 years than in individuals ≥ 45 years; while no significant differences were observed between non-obese and overweight/obesity individuals. Using time-dependent ROC analysis we also assessed the predictive value of METS-IR for future diabetes at a total of 11-time points between 2 and 12 years. The results showed that METS-IR had a higher predictive value for the future development of diabetes in women or individuals < 45 years of age compared to men or individuals ≥ 45 years of age for almost the entire follow-up period. Furthermore, across different BMI categories, we also found that in the short term (3–5 years), METS-IR had a higher predictive value for the development of diabetes in individuals with overweight/obesity, while in the medium to long term (6–12 years), METS-IR was more accurate in predicting the development of diabetes in non-obese individuals.ConclusionsOur study showed that METS-IR was independently associated with the development of future diabetes in a non-diabetic population. METS-IR was a good predictor of diabetes, especially for women and individuals < 45 years old for predicting the future risk of developing diabetes at all times.

Association Between Direct Oral Anticoagulant Score and Bleeding Events in Patients With Atrial Fibrillation Following Transcatheter Aortic Valve Replacement: A Retrospective Multicenter Cohort Study.

The Direct Oral Anticoagulant (DOAC) Score can predict bleeding risk in patients with atrial fibrillation taking DOACs; however, it lacks external validation. Therefore, this study aimed to assess the association between the DOAC Score and bleeding events in patients with atrial fibrillation who underwent transcatheter aortic valve replacement. This retrospective multicenter cohort study included patients with atrial fibrillation who underwent transcatheter aortic valve replacement, as registered in a Japanese multicenter registry. The primary end point was the incidence of bleeding. Patients were categorized based on their DOAC Score: low and moderate- (≤7 points), high- (8-9 points), and very high-risk (≥10 points) groups. Among 1230 patients (mean age 84.6±5.1 years; 457 men), 465 (37.8%) received a vitamin K antagonist, and the remaining patients received DOACs. The low and moderate-, high-, and very high-risk groups included 380 (30.1%), 497 (40.4%), and 353 patients (28.7%), respectively. The 3-year cumulative incidence of all bleeding events was significantly different among the 3 groups (low and moderate risk: 6.6%, high risk: 6.9%, and very high risk: 14.0%; P<0.01). Multivariable Cox regression analysis revealed that significant increments in the DOAC Score were associated with a risk of all bleeding events at 3 years in the overall cohort (hazard ratio [HR], 1.22 [95% CI, 1.08-1.38]; P<0.01), in the DOAC cohort (HR, 1.20 [95% CI, 1.01-1.42]; P=0.04), and in the vitamin K antagonist cohort (HR, 1.25 [95% CI, 1.04-1.50]; P=0.02). The DOAC Score was significantly associated with bleeding events in patients with atrial fibrillation after transcatheter aortic valve replacement, aiding in clinical decision-making for anticoagulant management. URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023585; Unique identifier: UMIN000020423.

Molecular characterization of PANoptosis-related genes associated with immune infiltration and prognosis in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic pulmonary disease with unknown pathogenesis and poor prognosis. PANoptosis, a newly identified form of inflammatory programmed cell death, has been implicated in various inflammatory lung diseases. This study aimed to identify differentially expressed PANoptosis-related genes (PRDEGs) associated with immune infiltration and prognosis in IPF, while also establishing a novel prognostic prediction model. A total of 63 PRDEGs were identified from GSE110147 dataset, with 31 exhibiting consistent expression trends in GSE213001. Enrichment analysis indicated that the majority of these PRDEGs were enriched in inflammatory and immune-related pathways. Three key PRDEGs—NLRP3, ATM, and VEGFA—were selected through univariate and multivariable Cox regression analyses. The prognostic prediction model developed from these key PRDEGs demonstrated robust predictive performance. Furthermore, the expression of most PRDEGs was positively correlated with pro-inflammatory immune cells, including macrophages, neutrophils, and CD4+ T cells. Validation of the expression levels of these key PRDEGs was conducted in fibrotic mouse lung tissue. This study suggests that PANoptosis plays a role in IPF, potentially linked to the infiltration of pro-inflammatory immune cells, and may influence disease progression through the regulation of inflammatory immune signaling pathway. A new prognostic prediction model for IPF based on PRDEGs was successfully developed.

Targeting LLT1 as a potential immunotherapy option for cancer patients non-responsive to existing checkpoint therapies in multiple solid tumors

BackgroundHigh levels of LLT1 expression have been found in several cancers, where it interacts with CD161 on NK cells to facilitate tumor immune escape. Targeting LLT1 could potentially relieve this inhibitory signal and enhance anti-tumor responses mediated through NK cells. Using the ‘The Cancer Genome Atlas’ (TCGA) database, we investigated the role of LLT1 in the tumor microenvironment (TME) across various cancers. Identifying such biomarkers could create new therapeutic options for patients in addition to complementing existing immunotherapies.MethodsLLT1 expression was evaluated in 33 cancers using TCGA transcriptome data. Univariate Cox regression analysis was employed to assess the correlation of LLT1 expression with patient survival. The relationship between LLT1 expression with immune infiltrates, immune gene signatures, and cancer genomic biomarkers (TMB, MSI, and MMR) was also investigated. Immunofluorescence studies were conducted to validate LLT1 expression in tumors. Furthermore, using the CRI iAtlas data, we evaluated LLT1 distribution and its correlation with other immune checkpoint genes in patients non-responsive to existing immune checkpoint therapies across multiple solid cancers.ResultsHigh expression of LLT1 was observed in 12 cancers, including BRCA, CHOL, ESCA, GBM, HNSC, KIRC, KIRP, LIHC, LUAD, STAD, SARC, and PCPG. In certain cancers like COAD, KICH, and KIRC, high LLT1 expression was associated with poor prognosis. Further analysis revealed that upregulated LLT1 was associated with an abundance of NK and T cell infiltrates in the TME, as well as exhaustive immune biomarkers, and inversely associated with pro-inflammatory and tumor suppressor signatures. High LLT1 expression is also positively correlated with genomic biomarkers in certain cancers. Immunofluorescence studies confirmed moderate to high LLT1 expression in immune-resistant prostate cancer, glioma, ovarian cancer, and immune-sensitive liver cancer cell lines. An independent assessment of clinical cohorts from CRI iAtlas showed a correlation of upregulated LLT1 with multiple immunosuppressive genes in patients non-responsive to current ICIs.ConclusionsThe biomarker analysis revealed a clear association between elevated LLT1 expression and an immunosuppressive TME in patient cohorts from TCGA and clinical databases. Therefore, this study provides a foundation for utilizing LLT1 as a potential target to improve clinical responses in ICI non-responsive patients with upregulated LLT1.

Complement C1S is a potential prognostic biomarker and associated with M2 macrophage infiltration in gliomas: From bioinformatics to comprehensive experimental validation

Glioma is the most common malignant tumor of the central nervous system, and the ability of traditional clinical treatment to prolong the survival of glioma patients is limited. A substantial body of evidence underscores the pivotal role of the immune system in eradicating malignant cells and impeding tumor metastasis. Consequently, tumor immunotherapy has become a promising avenue to address the clinical conundrum faced by glioma patients. The complement system is a natural immune system that is an important line of defense in the immune response. C1S plays a key role in activating the classical complement system. Nevertheless, few studies have focused on the role of C1S in glioma tumorigenesis and progression. In this study, we demonstrated that C1S was upregulated in GBM (Grade IV) and low-grade gliomas (LGG, Grade II-III) by combining glioma cohorts from multiple public databases with our internal independent cohorts and that increased C1S expression levels predict a poor prognosis for gliomas. Cox regression analysis identified C1S as an important prognostic indicator for glioma patients. In addition, gene functional enrichment analysis demonstrated that C1S was involved in cellular immunity, T-cell activation, macrophage differentiation, and cell proliferation. Further experiments demonstrated that C1S facilitates tumor cell proliferation, cell migration and intracranial tumor growth in nude mice. More importantly, we evaluated the role of C1S in immune infiltration. These results suggested that C1S was closely related to a variety of immune cell types in glioma, especially M2 macrophages. Our findings were further validated via glioma tissue microarray immunohistochemical analysis and an M2 macrophage infiltration assay. Together, these findings revealed the underlying critical role of C1S in glioma tumorigenesis, progression, and the tumor immune microenvironment, contributing to further understanding of glioma pathogenesis and guiding immunotherapy.

Biochemical recurrence after open radical prostatectomy in a single-center cohort with a minimum follow-up of 10 years

Purpose: To investigate the long-term oncological outcomes and report biochemical recurrence (BCR)-free survival for men who underwent open radical prostatectomy at a single center. Materials and methods: A total of 360 patients who underwent open radical prostatectomy at our institution between 2003 and 2011 were included in this study. The BCR-free survival rates were calculated by Kaplan-Meier method and log-rank analysis. Multivariable Cox regression models were used to test the effect of other factors such as age, preoperative prostate-specific antigen (PSA), Gleason score, and surgical margins on BCR. Results: Median patient age was 65.4 years, with a median preoperative PSA level of 6.21 ng/ml. Operating time had a median duration of 155.1 minutes, ranging from 104 to 301 minutes. Nerve-sparing surgery was achievable in 48.1% of patients, including 34.2% undergoing bilateral procedures and 13.9% unilateral. In terms of surgical precision and outcomes, the overall rate of positive surgical margins was 23.6%, which decreased significantly to 11.1% in patients with localized prostate cancer. Lymph node involvement occurred in 3.6% of cases. Postoperative care statistics revealed a median catheterization duration of 9.1 days (range: 4–30 days) and a low rate of significant complications (4.4%). The early continence rate in a standardized pad test was 80.6%. At a median follow-up of 150.5 months, the 5-year and 10-year BCR-free survival rates for the entire cohort were 91.4% and 77.5%, respectively. The 10-year BCR-free survival rates were 84.8%, 81.5%, and 68.5% for low-, intermediate-, and high-risk patients, respectively. Furthermore, the 10-year BCR-free survival rates were 78.8% and 62.8% for localized and locally advanced prostate cancer, respectively. Preoperative PSA &gt;20 ng/ml, postoperative Gleason sum ≥3 + 4, and positive surgical margins were associated with increased risk of BCR on multivariable Cox regression analysis. Conclusion: Our long-term oncological results match or exceed those previously published in similar contemporary cohorts with long follow-up.

Liquid-Liquid Phase Separation in the Prognosis of Lung Adenocarcinoma: An Integrated Analysis.

Lung adenocarcinoma (LUAD) is a highly lethal malignancy. Liquid-Liquid Phase Separation (LLPS) plays a crucial role in targeted therapies for lung cancer and in the progression of lung squamous cell carcinoma. However, the role of LLPS in the progression and prognosis of LUAD remains insufficiently explored. This study employed a multi-step approach to identify LLPS prognosis-related genes in LUAD. First, differential analysis, univariate Cox regression analysis, Random Survival For-est (RSF) method, and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regres-sion analysis were utilized to identify five LLPS prognosis-related genes. Subsequently, LASSO Cox regression was performed to establish a prognostic score termed the LLPS-related progno-sis score (LPRS). Comprehensive analyses were then conducted based on the LPRS, including survival analysis, clinical feature analysis, functional enrichment analysis, and tumor microenvi-ronment assessment. The LPRS was integrated with additional clinicopathological factors to de-velop a prognostic nomogram for LUAD patients. Immunohistochemical validation was per-formed on clinical tissue samples to further validate the findings. Finally, the relationship be-tween KRT6A, one of the identified genes, and epidermal growth factor receptor (EGFR) muta-tions was investigated. The LPRS was established using five LLPS-related genes: IGF2BP1, KRT6A, LDHA, PKP2, and PLK1. Higher LPRS was closely associated with poor survival outcomes, gender, progression-free survival (PFS), and advanced TNM stage. Furthermore, LPRS emerged as an independent prognostic factor for LUAD. A nomogram integrating LPRS, TNM stage, and age demonstrated remarkable predictive accuracy for prognosis among patients with LUAD. LLPS likely influences LUAD prognosis through the activity of IGF2BP1, KRT6A, LDHA, PKP2, and PLK1. KRT6A exhibits significant upregulation in LUAD, particularly in patients with EGFR mutations. This study introduces a novel LPRS model that demonstrates high accuracy in pre-dicting the clinical prognosis of LUAD. Moreover, the findings suggest that KRT6A may play a critical role in the LLPS-mediated malignant progression of LUAD.