A clinical tool to predict overall survival of elderly patients with soft tissue sarcoma after surgical resection.

With the aging world population, the incidence of soft tissue sarcoma (STS) in the elderly gradually increases and the prognosis is poor. The primary goal of this research was to analyze the relevant risk factors affecting the postoperative overall survival in elderly STS patients and to provide some guidance and assistance in clinical treatment. The study included 2,353 elderly STS patients from the Surveillance, Epidemiology, and End Results database. To find independent predictive variables, we employed the Cox proportional risk regression model. R software was used to develop and validate the nomogram model to predict postoperative overall survival. The performance and practical value of the nomogram were evaluated using calibration curves, the area under the curve, and decision curve analysis. Age, tumor primary site, disease stage, tumor size, tumor grade, N stage, and marital status, are the risk variables of postoperative overall survival, and the prognostic model was constructed on this basis. In the two sets, both calibration curves and receiver operating characteristic curves showed that the nomogram had high predictive accuracy and discriminative power, while decision curve analysis demonstrated that the model had good clinical usefulness. A predictive nomogram was designed and tested to evaluate postoperative overall survival in elderly STS patients. The nomogram allows clinical practitioners to more accurately evaluate the prognosis of individual patients, facilitates the progress of individualized treatment, and provides clinical guidance.

Breaking the Barriers of Therapy Resistance: Harnessing Ferroptosis for Effective Hepatocellular Carcinoma Therapy.

Ferroptosis is a type of cell death that relies on iron and is distinguished by the occurrence of lipid peroxidation and the buildup of reactive oxygen species. Ferroptosis has been demonstrated to have a significant impact on the advancement and resistance to treatment of hepatocellular carcinoma (HCC), thereby highlighting its potential as a viable therapeutic target. Ferroptosis was observed in HCC tissues in contrast to normal liver tissue. The inhibition of ferroptosis has been found to increase the viability of HCC cells and decrease their susceptibility to various anticancer therapies, including chemotherapy, radiotherapy, and immune checkpoint blockade. The administration of drugs that directly modulate ferroptosis regulators or induce excessive production of lipid-reactive oxygen species has demonstrated the potential to enhance the responsiveness of drug-resistant HCC cells to treatment. However, the precise mechanism underlying this phenomenon remains ambiguous. This review presents a comprehensive overview of the crucial role played by ferroptosis in enhancing the efficacy of treatment for hepatocellular carcinoma (HCC). The main aim of this study is to examine the feasibility of utilizing ferroptosis as a therapeutic approach to improve the efficacy of HCC treatment and overcome drug resistance.

Identification of Subtypes in Triple-negative Breast Cancer Based on Shared Genes Between Immunity and Cancer Stemness.

The correlation between triple-negative breast cancer (TNBC) and genes related to immunity and cancer stemness, particularly shared genes, remains unclear. This study aimed to investigate the correlation of immunity and cancer stemness with the molecular subtyping and survival rates in TNBC using bioinformatics approaches. Differential gene analysis was conducted to identify TNBC-associated differentially expressed genes (DEGs). Cancer stem cell (CSC)-related genes were obtained using weighted gene coexpression network analysis. Immune-related gene sets were retrieved from the literature. Venn analysis was performed to identify the shared DEGs between immunity and cancer stemness in TNBC. Cluster analysis and survival analysis based on the expression of these genes were conducted to identify TNBC subtypes with significant survival differences. A total of 5259 TNBC-associated DEGs, 2214 CSC-related genes, 1793 immune-related genes, and 44 shared DEGs between immunity and cancer stemness were obtained. Among them, 3 shared DEGs were closely associated with TNBC survival rates ( P <0.05). Cluster and survival analyses revealed that among 3 subtypes, cluster2 exhibited the best survival rate, and cluster3 showed the worst survival rate ( P <0.05). Dendritic cells were highly infiltrated in cluster2, while plasma cells and resting mast cells were highly infiltrated in cluster3 ( P <0.05). Genes shared by immunity and cancer stemness were capable of classifying TNBC samples. TNBC patients of different subtypes exhibited significant differences in immune profiles, genetic mutations, and drug sensitivity. These findings could provide new insights into the pathogenesis of TNBC, the immune microenvironment, and the selection of therapeutic targets for drug treatment.

The global, regional, and national disease burden of breast cancer attributable to tobacco from 1990 to 2019: a global burden of disease study.

OBJECTIVE: Tobacco has been identified as a significant contributory element to the development of breast cancer. Our objective was to evaluate the spatiotemporal trends of tobacco-related breast cancer at the global, regional, and national scales during 1990-2019. METHODS: We extracted data on mortality, disability adjusted of life years (DALYs), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR) from the Global Burden of Disease (GBD) study 2019. Estimated annual percentage change (EAPC) was computed to assess the temporal change in ASDR and ASMR. RESULTS: In 2019, the deaths and DALYs attributed to tobacco-related breast cancer were estimated to be 35,439 (95% UI: 22,179-48,119) and 1,060,590 (95% UI: 622,550-1,462,580), respectively. These figures accounted for 5.1% and 5.2% of the total burden of breast cancer. ASMR and ASDR increased in low SDI regions, remained stable in low-middle and middle SDI regions and declined in high and high-middle SDI regions. The burden of breast cancer attributable to tobacco varied notably among regions and nations. Oceania, Southern Latin America, and Central Europe were the GBD regions with the highest number of ASMR and DALYs. There was a positive relationship between age-standardized rate and SDI value in 2019 across 204 nations or territories. A negative association was observed between the EAPC in ASMR or ASDR and the human development index (HDI) in 2019 (R = -0.55, p < 0.01 for ASMR; R = -0.56, p < 0.01 for ASDR). CONCLUSION: Tobacco is one important and modifiable risk factor for breast cancer. The heterogeneity in both the spatial and temporal distribution can be attributed to factors such as aging, population growth, and SDI. These findings substantiate the necessity of expediting the enforcement of tobacco-free legislation in order to safeguard populations from the detrimental effects of tobacco.

The miR-146b-3p/TNFAIP2 axis regulates cell differentiation in acute myeloid leukaemia.

Our purpose is to verify that miR-146b-3p targets the downstream transcript TNFAIP2 in order to reveal the machinery underlying the miR-146b-3p/TNFAIP2 axis regulating acute myeloid leukaemia (AML) differentiation. Bioinformatics analyses were performed using multiple databases and R packages. The CD11b+ and CD14+ cell frequencies were detected using flow cytometry and immunofluorescence staining. The TNFAIP2 protein expression was evaluated using western blotting, immunocytochemistry and immunofluorescence staining. The qRT-PCR was conducted to detect the expression of TNFAIP2 and miR-146b-3p. TNFAIP2 and its correlated genes were enriched in multiple cell differentiation pathways. TNFAIP2 was upregulated upon leukaemic cell differentiation. miR-146b-3p directly targeted TNFAIP2, resulting in a decrease in TNFAIP2 expression. Forced expression of TNFAIP2 or knockdown of miR-146b-3p significantly induced the differentiation of MOLM-13 cells. In this study, we demonstrated that TNFAIP2 is a critical driver in inducing differentiation and that the miR-146b-3p/TNFAIP2 axis involves in regulating cell differentiation in AML.

Construction of a four-mRNA prognostic signature with its ceRNA network in CESC.

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) tumorigenesis involves a combination of multiple genetic alteration processes. Constructing a survival-associated competing endogenous RNA (ceRNA) network and a multi-mRNA-based prognostic signature model can help us better understand the complexity and genetic characteristics of CESC. In this study, the RNA-seq data and clinical information of CESC patients were downloaded from The Cancer Genome Atlas. Differentially expressed mRNAs, lncRNAs and miRNAs were identified with the edgeR R package. A four-mRNA prognostic signature was developed by multivariate Cox regression analysis. Kaplan-Meier survival with the log-rank tests was performed to assess survival rates. The relationships between overall survival (OS) and clinical parameters were evaluated by Cox regression analysis. A survival-associated ceRNA network was constructed with the multiMiR package and miRcode database. Kyoto encyclopedia of genes and genomes (KEGG) analysis and gene ontology analyses were used to identify the functional role of the ceRNA network in the prognosis of CESC. A total of 298 differentially expressed mRNAs, 8 miRNAs, and 29 lncRNAs were significantly associated with the prognosis of CESC. A prognostic signature model based on 4 mRNAs (OPN3, DAAM2, HENMT1, and CAVIN3) was developed, and the prognostic ability of this signature was indicated by the AUC of 0.726. Patients in the high-risk group exhibited significantly worse OS. The KEGG pathways, TGF-ß and Cell adhesion molecules, were significantly enriched. In this study, a CESC-associated ceRNA network was constructed, and a multi-mRNA-based prognostic model for CESC was developed based on the ceRNA network, providing a new perspective for cancer pathogenesis research.

Chinese Medicine Regulates DNA Methylation to Treat Haematological Malignancies: A New Paradigm of "State-Target Medicine".

Aberrant regulation of DNA methylation plays a crucial causative role in haematological malignancies (HMs). Targeted therapy, aiming for DNA methylation, is an effective mainstay of modern medicine; however, many issues remain to be addressed. The progress of epigenetic studies and the proposed theory of "state-target medicine" have provided conditions to form a new treatment paradigm that combines the "body state adjustment" of CM with targeted therapy. We discussed the correlation between Chinese medicine (CM) syndromes/states and DNA methylation in this paper. Additionally, the latest research findings on the intervention and regulation of DNA methylation in HMs, including the core targets, therapy status, CM compounds and active components of the Chinese materia medica were concisely summarized to establish a theoretical foundation of "state-target synchronous conditioning" pattern of integrative medicine for HMs, simultaneously leading a new perspective in clinical diagnosis and therapy.

Comprehensive analysis of the expression and prognosis for TNFAIPs in head and neck cancer.

Head and neck cancer (HNC) tumorigenesis involves a combination of multiple genetic alteration processes. Tumour necrosis factor-alpha-induced proteins (TNFAIPs) are involved in tumour development and progression, but few studies have been conducted on these factors in HNC. We aimed to analyse TNFAIPs and assess their potential as prognostic biomarkers and therapeutic targets using the Oncomine, UALCAN, Human Protein Atlas, LinkedOmics, cBioPortal, GeneMANIA, Enrichr, and Tumor IMmune Estimation Resource databases. We found that the transcript levels of TNFAIP1, TNFAIP3, EFNA1, TNFAIP6 and TNFAIP8 were increased, while those of TNFAIP8L3 and STEAP4 were reduced in HNC tissues versus normal tissues. The EFNA1, TNFAIP8 and TNFAIP8L3 expression levels were significantly correlated with the pathological stage. In HNC patients, high PTX3 and TNFAIP6 transcript levels were significantly associated with shorter overall survival (OS). Moreover, genetic alterations in TNFAIP1, TNFAIP6, and STEAP4 resulted in poorer disease-free survival, progression-free survival, and OS, respectively. TNFAIPs may mediate HNC tumorigenesis by regulating PI3K-Akt, Ras and other signalling pathways. TNFAIPs are also closely correlated with the infiltration of immune cells, including B cells, CD8+ T cells, CD4+ T cells, etc. The data above indicate that TNFAIPs may be potential biomarkers and therapeutic targets for HNC.

Cytotoxic T lymphocyte associated antigen 4 expression predicts poor prognosis in luminal B HER2-negative breast cancer.

Cytotoxic T lymphocyte associated antigen 4 (CTLA-4) serves an important role in inhibiting anti-tumor immune response in the majority of solid tumors. However, a limited number of studies reported the function of CTLA-4 in luminal B HER2-negative breast cancer. Immunohistochemistry was performed to evaluate the expression of tumor and interstitial CTLA-4 in luminal B HER2-negative breast cancer tissues. The percentage of patients with tumor and interstitial CTLA-4+ was 41.2% (42/102) and 46.1% (47/102), respectively. There was a positive association between tumor CTLA-4 expression and interstitial CTLA-4 expression (P<0.05). The disease-free survival (DFS) of the tumor CTLA-4+ group was significantly shorter compared with patients with tumor CTLA-4- (mean, 89.070 vs. 39.022 months; P<0.0001). Additionally, the DFS of interstitial CTLA-4+ group was shorter compared with the interstitial CTLA-4- group (mean, 85.526 vs. 46.574 months; P<0.0001). Tumor and interstitial CTLA-4 expression may have prognostic predicting value in luminal B HER2-negative breast cancer. The present study may provide the basis for the use of a CTLA-4 blocker in patients with luminal B HER2-negative breast cancer.

Correlation Between Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphisms and Pemetrexed Chemotherapy Efficacy/Toxicity in Non-Squamous Non-Small Cell Lung Cancer.

BACKGROUND In the present study, we aimed to retrospectively analyze the correlation between toxicity of pemetrexed (PEM) chemotherapy and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms in patients with advanced non-squamous non-small cell lung cancer (non-sq NSCLC). MATERIAL AND METHODS We used polymerase chain reaction, gene scanning, and restriction fragment length polymorphism to analyze MTHFR C677T in 51 patients with advanced non-sq NSCLC. The patients received chemotherapies with single-agent PEM (monotherapy group) or with PEM combined with cisplatin (joint group). The correlation between MTHFR C677T polymorphisms and chemotherapy efficacy/toxicity was also assessed. RESULTS There were 40 patients in the monotherapy group and 11 patients in the joint group. Among the 40 patients received single-agent PEM chemotherapy, those with the CT/TT genotype had higher incidence of leukopenia, neutropenia, nausea, and fatigue compared to patients with the with wild-type genotype CC (all P<0.05). However, polymorphisms of MTHFR C677T were not significantly associated with other adverse events and clinical outcomes. CONCLUSIONS Compared with genotype CC (the wild type), patients with the CT/TT genotype had higher incidence of leukopenia, neutropenia, nausea, and fatigue. Therefore, the MTHFR C677T polymorphism could be a predictive factor for leukopenia, neutropenia, nausea, and fatigue toxicities in non-sq NSCLC patients treated with single-agent PEM.