Independent Prognostic Risk Factor Research Articles

Knockdown of integrin β1 inhibits proliferation and promotes apoptosis in bladder cancer cells.

Bladder cancer (BC) is the most common urinary tract malignancy. Identifying biomarkers that predict prognosis and immune function in patients with BC can enhance our understanding of its pathogenesis and provide valuable guidance for diagnosis and treatment. Our findings indicate that increased ITGB1 expression is associated with higher clinical grade and stage, establishing ITGB1 as an independent prognostic risk factor for BC. Enrichment analysis revealed that the function of ITGB1 in BC was linked to the extracellular matrix. The experimental results showed that ITGB1 knockdown in the BC cell lines 5637 and RT112 reduced their proliferation, migration, and invasion. Furthermore, ITGB1 suppression promotes apoptosis in BC cells by inhibiting the PI3K-AKT pathway. A prognostic risk model incorporating CES1, NTNG1, SETBP1, and AIFM3 was developed based on ITGB1, this model can accurately predict patient prognosis based on immunological status. In conclusion, this study shows that knockdown of ITGB1 can restrain the migratory and invasive capabilities of BC cells and accelerate apoptosis, and this role might be associated with PI3K-AKT, highlighting its potential as a diagnostic marker and therapeutic target for BC.

PFAS promotes colorectal cancer progression via regulating RIG-I-mediated innate immune signalling

ObjectivePhosphoribosylformylglycinamidine synthase (PFAS) is a critical enzyme in de novo synthesis of purine. Innate immunity recognizes tumor derived damage-associated molecular patterns (DAMPs) and initiates the anti-tumor adaptive responses. While the function of PFAS catalyzed de novo synthesis of purine is well proved, its effect on innate immune evasion in cancer is unclear and needs to be further explored. The purpose of this study was to investigate the specific mechanisms by which PFAS inhibits RIG-I receptor (RLR) -mediated NF-κB axis in CRC. Materials and Methodsquantitative real-time PCR (qRT-PCR), Immunohistochemical (IHC) staining and western blotting were conducted to study the expression of PFAS in CRC tissues. Survival analysis, COX regression analysis and receiver operating characteristic (ROC) curve analysis were respectively conducted to assess correlation between the PFAS expression and clinicopathological characteristics, investigate the percent survival based on PFAS level in different clinical CRC groups, identify factors influencing the prognosis of CRC, and illustrate the diagnostic ability of PFAS in CRC patients. Furthermore, the CCK8 and transwell assays were carried out to study CRC cell function affected by PFAS. Mechanistically, plaque assay was used to assess the regulation of PFAS on innate immune signalling. The inhibition of PFAS on RIG-I-mediated innate immune signalling was further investigated by qRT-PCR and reporter assays in thepresence of lentiviral-mediated PFAS stably knocking down and stably overexpressing. Lastly, the interaction between PFAS and RIG-I was verified by co-immunoprecipitation assay. ResultsThe expression of PFAS in CRC tissue was higher than in adjacent normal colorectal tissue. The level of PFAS expression was significantly associated with stage-AJCC, regional lymph nodes metastasis and recurrence in CRC. Low expression of gene PFAS caused better survival than high expression in CRC patients. PFAS could be considered as an independent prognostic risk factor of CRC. PFAS promote cell proliferation and invasion of CRC cell lines. According to ROC curve analysis, PFAS could be used as a diagnostic biomarker in CRC. Mechanistically, PFAS inhibit interferon-β (IFN-β) gene and interferon-stimulated gene 56 (ISG56) expression. Furthermore, we confirmed that PFAS target RIG-I to inhibit RIG-I-mediated innate immune signalling.

KRT80 in hepatocellular carcinoma plays oncogenic role via epithelial-mesenchymal transition and PI3K/AKT pathway.

Hepatocellular carcinoma (HCC), a globally prevalent form of cancer, is featured by aggressive growth and early metastasis. Elucidating the underlying mechanism and identifying the effective therapy are critical for advanced HCC patients. In the study, we detect that KRT80 was upregulated in HCC samples. HCC patients with higher KRT80 are associated with worse overall survival after surgery. Gain-of and loss-of function studies show that KRT80 enhanced HCC cells proliferation, migration, invasion, and angiogenesis, whereas its silencing abolishes the effects in vivo and in vitro. Mechanistic investigation shows that KRT80 may function as an independent prognostic risk factor and act as an oncogene by influencing EMT and modulating the PI3K/AKT signaling pathway. Together, these findings suggest that KRT80 may be a potential oncogene and a good indicator in predicting prognosis. Targeting KRT80 can offer new insights into the prevention and treatment of HCC.

Ratio of red blood cell distribution width to albumin level and risk of mortality in sarcopenic obesity

The aim of this study was to investigate the relationship between red blood cell distribution width and albumin ratio (RAR) levels and mortality in adult patients with sarcopenic obesity in the United States. The study included 1,361 adult patients with sarcopenic obesity from the National Health and Nutrition Examination Survey (1999–2006). The X-tile was used to determine the optimal subgroup thresholds for RAR values, and propensity score matching (PSM) was employed to reduce baseline bias. Cox regression analysis, Kaplan-Meier survival curves, and restricted cubic spline analysis were utilized to assess the relationship between RAR levels and all-cause and cardiovascular mortality. Subgroup analysis and the Subpopulation Treatment Effect Pattern Plot were employed to determine survival advantages across different subgroups. Time-dependent ROC analysis to evaluate the accuracy of RAR level in predicting survival outcomes at different time points. Post-PSM multifactorial Cox regression analyses revealed that RAR was a significant independent predictor of all-cause mortality (HR 1.487, 95% CI: 1.259–1.756) and an independent risk factor for cardiovascular mortality (HR 1.487, 95% CI: 1.260–1.758) in patients with sarcopenic obesity. The survival advantage was consistent across subgroups. Restricted cubic spline analysis indicated an approximate S-shaped association between RAR levels and mortality. Time-dependent ROC curves demonstrate that the areas under the all-cause mortality curves at the RAR level for 1-year, 3-year, 5-year, and 10-year are 0.79, 0.66, 0.64, and 0.63, respectively. The areas under the cardiovascular mortality curve are 0.80, 0.70, 0.66, and 0.61, respectively. Moreover, in comparison to the baseline model lacking covariates, the AUC values of the joint model exhibited heightened levels at various time points. Therefore, We demonstrated that the RAR level is an independent prognostic factor for mortality risk in the American population with sarcopenic obesity, and it is reasonable to consider the RAR level as a simple and effective risk prediction tool.

LOXL1 promotes gastric cancer progression by β-catenin-cyclinD mediated proliferation

Although much progress has been made in chemotherapy or target therapy for advanced gastric cancer, the prognosis is still poor. It is necessary to screen biomarkers for early diagnosis and prognosis prediction. However, the prognostic value of LOX family in gastric cancer and the underlying molecular mechanisms for promoting the progression of gastric cancer remains unclear. Among five members of LOX family, LOXL1 was the unique independent prognostic risk factor. The nomogram established based on the expression of LOXL1 and other clinical parameters could predict the overall survival rate of gastric cancer. Knockdown (KD) of LOXL1 decreased cell proliferation and led to G1 phase arrest in gastric cells. According to GSEA analysis that LOXL1 was positively correlated with the WNT signaling pathway, in vitro experiment proved that LOXL1-KD reduced the phosphorylation level of β-catenin and the expression of the downstream G1 phase checkpoint CCND1. In conclusion, LOXL1 has been identified as a potential risk prognostic biomarker for gastric cancer by promoting gastric cancer proliferation via WNT/β-catenin/cyclinD1 pathway.

Prognostic significance of collagen content in solitary fibrous tumors of the central nervous system.

We aimed to explore the prognostic significance of collagen content in solitary fibrous tumors (SFTs) of the central nervous system (CNS) and preliminarily investigate its relationship with magnetic resonance imaging (MRI) features of SFTs. Collagen content was identified using Masson's trichrome staining, and quantitatively assessed. Radiomic methods were applied to extract quantitative MRI features of SFTs, which were then analyzed in relation to collagen content. The collagen content in CNS SFTs was categorized into high- and low-content groups, with a cutoff value of 6%. Survival analysis indicated a positive correlation between collagen content and overall survival (OS). In multivariate Cox regression analysis, incorporating factors such as mitosis, necrosis, Ki67, and collagen content and other indicators, collagen content emerged as an independent prognostic factor. Collagen content demonstrated a negative correlation with tumor histological phenotype, Ki67, WHO grade, mitosis, necrosis, and brain invasion. Additionally, the signal intensity of SFTs on T2-weighted imaging (T2WI) decreased with increasing collagen content. Radiomics analysis identified 1,702 features from each patient's region of interest, with 12 features showing significant differences between the high and low collagen content groups. Among the quantitative parameters and radiomic models, the combined T1- and T2WI models exhibited the highest diagnostic performance. These findings suggest that collagen content is an independent prognostic risk factor for OS. Furthermore, combined radiomic models based on T1-and T2WI sequences may offer a more comprehensive, objective, and accurate assessment of collagen content in CNS SFTs.

Abstract 4129533: Phenotypes and clinical outcome of heart failure with preserved ejection fraction (HFpEF) patients in China: Findings from the Chinese Cardiovascular Association Database-Heart Failure Center Registry

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogenous syndrome with 5 phenotypes. We aimed to evaluate the clinical outcome of HFpEF patients with various phenotypes in China. Methods and Results: Data from the Chinese Cardiovascular Association (CCA) Database-HF Center Registry between January 2017 and December 2021 were analyzed, 51,466 hospitalized HFpEF patients with 1-year follow-up results were included in this analysis. The patients were categorized into five phenotypes based on published phenotyping method. Clinical characteristics and 1-year outcome and related risk factors of HFpEF patients with various phenotypes were explored. Results demonstrated significant differences in baseline characteristics and clinical outcomes among the phenotypes, patients with phenotype-3 (right heart and pulmonary-related HFpEF), phenotype-4 (valvular- and rhythm-related HFpEF) and phenotype-5 (extracardiac disease-related HFpEF) exhibited high incidence of adverse outcomes. Phenotype-3 and -4 exhibited high risk of heart failure rehospitalization, whereas phenotype-5 showed high cardiovascular mortality. The independent prognostic risk factors varied across different phenotypes as well. Conclusion: One-year outcome differs among HFpEF patients with various phenotyping. Future studies are warranted to validate if personalized treatment strategies based on HFpEF phenotypes could improve the individual outcome of HFpEF patients, especially for phenotype-3, -4 and -5 HFpEF patients. Keywords: Heart failure with preserved ejection fraction, phenotype, prognosis, population study, risk factors.

Pan-cancer landscape analysis of NOP58 and its oncogenic driving role in lung adenocarcinoma

Despite improvements in treatment in recent years, patients with lung adenocarcinoma (LUAD) still face poor prognoses. In this study, we elucidated the potential role of NOP58 ribonucleoprotein in pan-cancer and validated its oncogenic significance in LUAD using bioinformatics and in vitro and in vivo functional assays. NOP58 was found to be overexpressed in various types of tumors. It had great precision for predicting 20 distinct cancer types using receiver operating characteristic curve (ROC) as well as significant connections with the prognoses in particular cancers. In LUAD, NOP58 expression was correlated substantially with the TNM stage, pathologic stage, smoking status, and effectiveness endpoints, when we analyzed its association with clinical characteristics in LUAD. Elevated NOP58 expression was shown as connected with Th2 cell infiltration while also negatively linked with infiltrating other immune cells, such as CD8 T, cytotoxic, and Th1. By inhibiting NOP58 within the LUAD cells, we found a decrease in cells’ capability to proliferate, migrate, and invade. Knockdown of NOP58 inhibited tumor growth in mouse xenograft models. Furthermore, the tissue microarray study indicated that there was a greater expression of NOP58 in the tumor tissues compared to adjacent normal tissues in LUAD. Our findings revealed that NOP58 could be an outstanding bio-index for pan-cancer diagnosis and prognosis and an independent prognostic risk factor in LUAD.

Effect of MPP2 and its DNA methylation levels on prognosis of colorectal cancer patients

Colorectal cancer is one of the common malignant tumors with poor prognosis, which is partly due to the lack of an effective biomarker. The purpose of this study is to explore the impact of membrane palmitoylated protein (MPP2) on the prognosis of colorectal cancer patients. We obtained transcriptome data and DNA methylation data of 380 colorectal cancer patients from the Cancer Genome Atlas (TCGA). Then we used a series of bioinformatics analysis methods to reveal the relationship between MPP2 expression, DNA methylation sites, prognosis, immune checkpoint and clinical characteristics of patients. Finally, in vitro experiment and the meta-analysis of thousands of patients further confirmed the impact of MPP2 on the prognosis of colorectal cancer patients and cell migration and proliferation. The expression level of MPP2 is negatively regulated by its DNA methylation sites, which leads to its low expression in colorectal cancer. High expression of MPP2 is an independent prognostic risk factor, which may be a biomarker for colorectal cancer. Moreover, the expression of MPP2 shows a close relationship with immune checkpoint or immune cells infiltration, especially CD4+T cells. In addition, meta-analysis involving 1584 patients from four different data further confirmed that MPP2 was a risk factor for colorectal cancer. Finally, knockdown of MPP2 could significantly inhibit the proliferation of SW480 cells via mTOR signaling pathway. This study was the first to suggest that MPP2 may become a promising biomarker, and has an important role in immune checkpoint or immune cell infiltration in colorectal cancer.

Bioinformatic analysis constructs an optimal prognostic index for survival-related variables (OPISV) based on whole-genome expression data in Glioblastoma

PurposeUsing clinical information and transcriptomic sequencing data from glioblastoma (GBM) patients in the TCGA database to perform gene-by-gene analysis that is aligned with individual patient characteristics and develop an optimal prognostic index of survival-related variables (OPISV) through iterative machine learning techniques to predict the prognosis of GBM patients. Study designThe TCGA dataset was utilized as the training dataset, while two GEO datasets served as independent validation cohorts. Initially, survival analysis (p < 0.001***), differential gene expression analysis (p < 0.05*), and univariate Cox regression analysis (p < 0.05*) were employed to identify genes that are highly correlated with patient prognosis and exhibit significant differences in survival status. Subsequently, incorporating the non-excludable variable of age, a multivariate Cox regression analysis was performed in a stepwise manner to construct the OPISV. Finally, logistic and LASSO regressions were used to validate the association between the identified genes and patient survival. The OPISV performance is evaluated and its potential mechanisms are explored. ResultsAge, CTSD, PTPRN, PTPRN2, NSUN5, DNAJC30 and SOX21 emerged as the optimal variables through multivariate Cox regression iterations. Further analysis characterized Age, PTPRN and DNAJC30 as independent prognostic risk factors for constructing OPISV, which is validated with external GEO datasets and GEPIA database. In OPISV_high populations, significantly upregulated GABAergic synapse function was exposed. Differential genes identified from gene clustering of the GABAergic synapse pathway and gene module highly correlated with GABAergic synapse in the WGCNA analysis are pointing unequivocally to the glioma progress. ConclusionOPISV is feasible for predicting patient survival, as it may serve as a potential mechanism underlying the involvement of GABAergic synapses in the progression of GBM.

Mobile stroke units based on rural emergency medical stations for pre-hospital intravenous thrombolysis of stroke in remote areas

ABSTRACT Objectives To explore a novel model of mobile stroke units (MSUs) integrated with rural emergency medical stations for pre-hospital care of stroke patients in remote areas. Methods We used MSUs + Ambulance mode, where both the MSUs and conventional ambulances are sent to the patient’s location. The conventional ambulance coordinates with the MSUs to choose the fastest route to meet and transfer the patient at the point along the way. We collected data from 149 patients from March 2022 to April 2023, including National Institutes of Health Stroke Scale (NIHSS) scores (on admission, 24 hours, day 7), 90-day modified Rankin Scale (mRS) scores, and other clinical variables. We performed propensity score matching (PSM) to balance the potential confounding variables between groups. Results We found that the MSUs + Ambulance mode (OR = 12.507, 95% confidence interval [CI] [3.633, 43.061], p < 0.001) and admission NIHSS score (OR = 0.583, 95% CI [0.493, 0.690], p < 0.001) were independent prognostic risk factors for stroke patients. The MSUs + Ambulance mode reduced NIHSS scores 7 days prior to admission (OR = 0.679, 95% CI [0.563, 0.819], p < 0.001). After PSM, patients who received MSUs + Ambulance mode had a better prognosis (χ2 = 9.573, p = 0.004), as well as a lower mRS score at 90 days (Z = -3.371, p = 0.001). Conclusions MSUs integrated with rural emergency medical stations show the feasibility and potential benefits of pre-hospital intravenous thrombolysis for stroke patients in geographically distant regions.

Development of a modified nutritional index model based on nutritional status and sarcopenia to predict long-term survival and chemotherapy benefits in elderly patients with advanced gastric cancer

BackgroundElderly patients with advanced gastric cancer have poor prognoses. This study aims to develop a prediction model for long-term survival after radical surgery and to identify patients who may benefit from chemotherapy. MethodsData from 555 elderly patients with advanced gastric cancer admitted to two medical centers from 2009 to 2018 were retrospectively analyzed. Sarcopenia was combined with the Controlling Nutritional Status (CONUT) score to create a modified nutritional index (mCONUT). Cox regression analyses were used to develop a novel nomogram prediction model (mCNS) that combined mCONUT, pN, and tumor size, and its performance was further verified both internally and externally. ResultsMultivariate Cox analysis revealed that tumor size, pN, and mCONUT were independent prognostic risk factors for overall survival (OS). The mCNS model showed good fit and high predictive value (AUC: training set 0.711; validation set 0.707), outperforming the pTNM model (p<0.05). To further investigate the association between the model and adjuvant chemotherapy, we categorized the model into two risk groups : a high-risk group and a low-risk group. Further analysis revealed that, in the low-risk group, the OS and recurrence-free survival(RFS) for patients receiving adjuvant chemotherapy was significantly better than that of those who did not receive chemotherapy (p=0.047,p=0.019). In the high-risk group, this result was not observed (p=0.120, p=0.053). ConclusionThe mCNS model has high predictive value in predicting long-term survival of elderly patients with advanced gastric cancer. Patients with mCNS-L were able to benefit from chemotherapy after laparoscopic radical gastrectomy.

M6A-related genes ALKBH5 and RBMX as prognostic and progression biomarkers in Chinese oral squamous cell carcinoma patients

ObjectiveN6-methyladenosine (m6A) RNA dysregulation is crucial for cancer development. The study aimed to explore the effects of m6A modification in oral squamous cell carcinoma (OSCC) and its potential as a biomarker and therapeutic target. DesignWe first analyzed m6A-related gene expression and its impact on OSCC prognosis and progression using the TCGA database. Subsequently, a Chinese cohort of 134 samples was used for validation. Bioinformatics analysis was conducted with TCGA data, and m6A levels were measured in the validation cohort using a quantification kit. Survival analysis was performed to study the relationship between m6A-related genes and OSCC prognosis in the Chinese population. The expression of m6A-related genes was assessed by using quantitative real-time PCR, Western blot analysis, and immunohistochemistry. ResultsIn the TCGA database, we found dysregulated expressions of METTL14, ALKBH5, YTHDF2, HNRNPC, LRPPRC, HNRNPA2B1, IGF2BP2, and RBMX in OSCC. Based on this, we observed significantly elevated total m6A content in OSCC tissues compared to normal controls in the validation cohort. Among the m6A candidate genes, only ALKBH5 and RBMX upregulation were found to be independent prognostic risk factors for poor OSCC survival in the Chinese population. And the inclusion of these two genes had a higher area under the curve for 3-year (0.705, 0.826), and 5-year (0.715, 0.788) overall survival compared to the model that only considered clinical parameters. ConclusionsWe found the upregulation of m6A status in OSCC, of which, ALKBH5 and RBMX may serve as promising diagnostic and prognostic biomarkers for Chinese patients with OSCC.

The impact of cathepsins on liver hepatocellular carcinoma: Insights from genetic and functional analyses

Liver Hepatocellular Carcinoma (LIHC), ranked as the second deadliest cancer globally, poses a major health challenge because of its widespread occurrence and poor prognosis. The mechanisms underlying LIHC development and progression remain unclear. Cathepsins are linked to tumorigenesis in other cancers, but their role in LIHC is underexplored. This study employed integrative analyses, including Mendelian Randomization (MR), bulk RNA-sequencing (bulk-seq), single-cell RNA sequencing (scRNA-seq), immunohistochemical (IHC) analysis, and cellular experiments with siRNA technology, to investigate the role of cathepsin E (CTSE) in LIHC. MR analysis identified CTSE as a factor associated with increased LIHC risk. Prognostic analysis using TCGA data showed that higher CTSE levels are linked to poorer survival, establishing CTSE as an independent prognostic risk factor. Integrative transcriptome analysis revealed close relation of CTSE to the extracellular matrix. scRNA-seq from TISCH2 demonstrated that CTSE is predominantly expressed in malignant LIHC cells. IHC confirmed higher CTSE expression in LIHC tissues compared to peritumoral tissues. Functional assays, such as qRT-PCR, Western blot, cell proliferation, and colony formation experiments, demonstrated that siRNA-mediated CTSE knockdown in HepG2 and Huh7 cell lines notably suppressed cell proliferation and altered the FAK/Paxillin/Akt signaling cascade. This research enhances our comprehension of LIHC development, emphasizing CTSE as a promising prognostic marker and potential therapeutic target. Inhibiting CTSE could slow the progression of LIHC, presenting novel opportunities for therapeutic approaches.

Prognostic value of neutrophil-to-lymphocyte ratio and cardiac troponin I in patients with immune checkpoint inhibitors-related myocarditis

Abstract Background Over the past decade, immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment. However, ICIs inevitably may cause a spectrum of immune-related adverse events, among which cardiovascular toxicity, particularly myocarditis, while infrequent, has garnered increasing attention due to its high fatality rate. Purpose We executed a multicenter study aimed at characterizing ICI-related myocarditis and risk factors influencing its prognosis. Methods The study included patients with ICIs-associated myocarditis at four medical centers in China from January 28, 2019 to June 15, 2023. Logistic regression was performed to explore the risk factors for the development of severe myocarditis. Receiver operating characteristic curves were conducted to assess the diagnostic abilities of biomarkers to distinguish severe myocarditis, and the performance and calibration were evaluated using Hosmer-Lemeshow test. Cox regression analysis was employed to investigate the influential risk factors affecting the prognosis of ICI-related myocarditis. Kaplan-Meier survival curve analyses were conducted to assess the differences in survival times among different myocarditis groups. Results 35 ICIs-associated myocarditis patients were identified. 21 patients (60%) were classified as severe myocarditis, and they presented higher cardiac troponin I (cTnI) levels (P=0.013), higher N-terminal pro-B-type natriuretic peptide levels (P=0.031), higher creatine kinase (CK) levels (P=0.018), higher CK-MB levels (P=0.026), and higher neutrophil to lymphocyte ratio (NLR) levels (P=0.016) compared to non-severe myocarditis patients. Multivariate logistic regression showed that cTnI (adjusted odds ratio: 1.021, 95% confidence interval (CI): 1.002-1.039, P=0.03) and NLR (adjusted odds ratio: 1.890, 95% CI: 1.026-3.483, P=0.041) were the independent risk factors of ICI-associated severe myocarditis. The receiver operating characteristic curve showed an area under curve of 0.765 (95% CI: 0.601 to 0.929, P=0.013) for cTnI, and 0.773 for NLR (95% CI: 0.597 to 0.948, P=0.016). Multivariate COX regression showed that NLR (adjusted hazard ratio: 1.189, 95% CI: 1.028-1.376, P=0.020) and pneumonitis (adjusted hazard ratio: 8.142, 95% CI: 1.191-55.651, P=0.032) were the independent prognostic risk factor associated ICI- related myocarditis. Further Kaplan-Meier survival curve analysis showed that the survival rate among patients without pneumonitis and with low level of NLR significantly outstripped that of patients with pneumonitis (P=0.015) and high level of NLR (P=0.024). Conclusions As independent risk factors for the development of ICI-associated severe myocarditis, cTnI and NLR demonstrated a promising predictive utility for the identification of ICI-associated severe myocarditis. NLR and the presence of pneumonitis were identified as independent risk factors that significantly impacted the prognosis of ICI-related myocarditis.

Intraoperative radiotherapy might not serve as a standard therapy for retroperitoneal liposarcoma: insights from a population-based propensity score-matched study.

Difficulty in achieving complete resection leads to a poor prognosis for retroperitoneal soft tissue sarcoma, hence emphasizing the significance of adjuvant treatment. The benefit of preoperative radiotherapy for retroperitoneal liposarcoma was initially demonstrated by the STRASS trial. However, the impact of intraoperative radiotherapy (IORT) on retroperitoneal liposarcoma remains unexplored. Patients with retroperitoneal liposarcoma were identified in the Surveillance, Epidemiology, and End Results (SEER) database, treated between 2000 and 2019. Subsequently, a 1:1 propensity score-matched (PSM) analysis was conducted based on variables identified from a multivariate analysis. T-tests were used to assess differences in normally distributed continuous variables, while the rank-sum test was applied to variables that did not follow a normal distribution. The chi-squared test was utilized to evaluate differences in categorical variables. Ultimately, survival analysis was performed using SPSS to evaluate patient prognosis. A total of 2129 patients with retroperitoneal liposarcoma were included in our study. Age, sex, histology, grading, chemotherapy, and tumor size as independent prognostic risk factors for these patients through multivariate Cox regression analysis. Subsequently, 66 patients were included in the survival analysis through PSM, with 33 patients receiving IORT. Finally, the survival analysis revealed that there was no difference in overall survival among patients with retroperitoneal liposarcoma, regardless of whether they received IORT or not (p= 0.711). As an exploratory study, our findings suggest that patients may not derive benefit from intraoperative radiotherapy. These observations are intended to lay the groundwork for future prospective clinical studies.

DNA methylation-driven gene FAM3D promotes colorectal cancer growth via the ATF4-SESN2-mTORC1 pathway.

Globally, colorectal cancer (CRC) is the malignant tumor with the highest mortality rate after lung cancer. Abnormal DNA methylation drives dysregulated gene expression, thereby promoting CRC progression and leading to poor prognosis. We identified a 3-CpG methylation signature that is independently associated with CRC prognosis. The model consists of three methylation-driven genes: FAM3 Metabolism Regulating Signaling Molecule D (FAM3D), DAPP1, and PIGR. However, the prognostic significance, biological function, and related mechanisms of the individual methylation-driven gene FAM3D in CRC have not been studied. Here, we discovered that FAM3D expression was reduced in CRC tissues and cells, and that high methylation and low expression of FAM3D were independent prognostic risk factors for CRC. In addition, FAM3D promoted the growth and movement of CRC cells in vitro and the proliferation in nude mice, mainly by inhibiting ATF4 transcription and downregulating SESN2 expression, and ultimately activating mTORC1. Furthermore, FAM3D resulted in reduced sensitivity of CRC cells to oxaliplatin, cisplatin, and 5-fluorouracil. Our study showed that FAM3D activates the mTORC1 pathway through the ATF4-SESN2 axis and promotes the malignant progression of CRC, which contributes to predict CRC prognosis and guide individualized treatment.

Grading carcinoembryonic antigen levels can enhance the effectiveness of prognostic stratification in patients with colorectal cancer: a single-centre retrospective study.

This study developed a refined carcinoembryonic antigen (CEA) grading system using CEA cut-off points of 5, 20 and 50 ng/mL and to explore the prognostic value of CEA grading in predicting the progression-free survival (PFS) and overall survival (OS) of colorectal cancer (CRC) patients. A retrospective cohort study. First Affiliated Hospital of Guangxi Medical University. 1107 CRC patients who received surgical treatment. Survival analysis was conducted using the Kaplan-Meier method and compared using the log-rank test. A Cox regression model with a 95% CI was used to evaluate the independent prognostic risk factors for CRC. Prognostic nomograms were constructed to predict the 1-5-year PFS/OS. Elevated serum CEA levels are often indicative of recurrence and death in CRC patients. Higher CEA levels were significantly associated with more aggressive tumour phenotypes. The CEA grading system was an independent predictor of prognosis in CRC patients and effectively stratified PFS (62.0% vs 51.2% vs 33.7% vs 20.2%, p<0.001) and OS (64.7% vs 54.4% vs 36.6% vs 22.5%, p<0.001) in CRC patients. As the CEA grade increased, the risk of poor prognosis gradually increased in a gradient manner, with an approximately 10% difference in risk grade between each CEA grade. The internal validation cohort further confirmed that CEA grade remains an effective prognostic factor for the survival of CRC patients. Prognostic nomograms, which integrate individual characteristics, tumour features and CEA grading, provide a more comprehensive prognostic evaluation for CRC patients. The CEA grading system is an independent predictor of prognosis for CRC patients and can effectively stratify PFS and OS.

Impact of dynamic changes of tumor marker in neoadjuvant chemotherapy-treated triple-negative gastric cancer patients: a multi-center study

BackgroundIndependent and valid prognostic predictors for locally advanced gastric cancer (LAGC) patients with non-elevated serum tumor markers (Triple-negative: CA199 < 37U/ml, CEA < 5 µg/ml and CA125 < 35U/ml) before and after neoadjuvant chemotherapy (NACT) remain unclear.MethodsA total of 352 LAGC patients treated with NACT(NLAGC) from two centers were included. Of the 156 were Triple-negative patients. CA72-4 trajectory groupings was defined as longitudinal changes in CA72-4 levels before and after NACT to identify different potential subgroups and to compare recurrence-free survival (RFS) and overall survival (OS) among subgroups. The predictive performance of the nomogram-trajectory was evaluated using the area under the receiver operating characteristic curve(AUC), decision curve analysis, and C-index.ResultsIn the Triple-negative patients, the Stable group had significantly worse 3-year OS than the Normal, Elevated, and Descend groups(3-year OS: 53.9% vs. 77.9% vs. 73.5% vs. 87.7%;P = 0.002). Cox multivariate analysis showed that CA72-4 trajectory groupings (Stable group: HR:3.442, 95%CI[1.574–7.528], P = 0.002) was an independent prognostic risk factor. In addition, the C-index and AUC values based on the nomogram-trajectory were significantly higher than those of ypTNM staging (C-index: 0.788 vs. 0.719,P < 0.001;AUC: 0.800 vs. 0.667,P < 0.001). Furthermore, The survival analysis revealed that the 3-year OS of the Low-Risk group of nomogram scores was significantly better than that of the High-Risk group(3-year OS:84.7% vs. 29.1%). And the Low-Risk group had the lower cumulative risk of recurrence (P < 0.001).ConclusionThe CA72-4 trajectory groupings were an independent prognostic factor for NLAGC Triple-negative patients. The predictive efficacy of the Nomogram-trajectory was significantly better than the ypTNM.

Impact of sarcopenia on the prognosis of patients with advanced non-small cell lung cancer treated with antiangiogenic therapy: A propensity score matching analysis.

Limited information is available regarding the impact of sarcopenia on the prognosis of antiangiogenic therapy in individuals with advanced non-small cell lung cancer (NSCLC). This study primarily sought to examine the prognostic significance of sarcopenia in individuals with advanced NSCLC undergoing antiangiogenic therapy. We retrospectively enrolled all patients who met the inclusion and exclusion criteria from 2019 to 2021 at Nantong University Hospital. Patients were grouped according to the presence or absence of sarcopenia. After propensity score matching (PSM), progression-free survival (PFS), overall survival (OS), and adverse event rates were compared between the two groups. Factors associated with prognosis were screened using univariate and multivariate analyses. A total of 267 patients were included, with a total of 201 matched at baseline after PSM (77 in the sarcopenia group and 124 in the non-sarcopenia group). The sarcopenia group had lower PFS (p = 0.043) and OS (p = 0.011) than the non-sarcopenia group and a higher incidence of adverse events (p = 0.044). Multivariate analysis suggested that sarcopenia is an independent prognostic risk factor for OS in advanced NSCLC patients receiving antiangiogenic therapies (p = 0.009). Results of subgroup analyses showed some differences in the impact of sarcopenia on survival prognosis in populations with different characteristics. Patients with advanced NSCLC with comorbid sarcopenia exhibit a worse prognosis when treated with antiangiogenic therapy, and preventing and ameliorating sarcopenia may lead to better survival outcomes in patients with advanced NSCLC.