Occurrence Of Carcinoma Research Articles

Abnormal protein SUMOylation in liver disease: novel target for therapy.

SUMOylation is an important protein post-translational modification (PTM) process, in which the small ubiquitin-like modifier (SUMO) protein covalently binds to the target protein and regulates stability, subcellular localization, and protein-protein interaction of the target protein. Protein SUMOylation exerts crucial regulatory function in the liver, and its abnormalities are associated with various liver-related disease processes. This review focuses on the biological functions of protein SUMOylation in liver-related diseases in recent years, summarizes the molecular mechanisms of SUMOylation in the replication of hepatitis viruses and the occurrence of hepatocellular carcinoma, and discusses the significance of SUMOylation in liver-related disorders, which is essential for understanding liver biological processes and formulating therapeutic strategies.

Ascitic microbiota alteration is associated with portal vein tumor thrombosis occurrence and prognosis in hepatocellular carcinoma.

Portal vein tumor thrombosis (PVTT) frequently leads to malignant ascites (MA) in individuals with hepatocellular carcinoma (HCC), remaining a bottleneck in the treatment. This study aimed to explore the differences in microbes in paired groups and provide novel insights into PVTT and MA-related treatments. Formalin-fixed paraffin embedding ascite samples were collected from MA secondary to HCC and benign ascites (BA) secondary to liver cirrhosis (LC). Ascitic microbiota profiles were determined in the HCC and LC groups by 16S rRNA sequencing. Prognostic risk factors were screened using survival analysis. The correlation between the significantly different microbial signatures in the groups with PVTT (WVT) and non-PVTT (NVT) and clinical characteristics was explored. The expression of different immune cells was determined by labeling four markers in the MA tissue chips using multiplex immunohistochemistry. A total of 240 patients (196 with HCC with MA and 44 with LC with BA) were included in this study. Microbial profiles differed between the HCC and LC groups. PVTT and Barcelona Clinic Liver Cancer stage were shown to be prognostic risk factors. Significant differences in the alpha and beta diversities were observed between the WVT and NVT groups. Gammaproteobacteria and Acinetobacter were the most abundant in the HCC MA. Differences in microbial signatures between the WVT and NVT groups were correlated with the level of C-reactive protein and apolipoprotein A1. This study revealed the microbial differences in the tumor microenvironment of MA secondary to HCC and BA secondary to LC.IMPORTANCEFirst, we explored the alteration of the ascites ecosystem through the microbiota in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. Second, this is the first clinical study to investigate the differences between patients with HCC with and without portal vein tumor thrombosis via 16S rRNA sequencing. These results revealed a decreased microbial diversity and metabolic dysregulation in individuals with HCC and portal vein tumor thrombosis. Gammaproteobacteria and Acinetobacter were the most abundant in the HCC malignant ascitic fluid. Our study provides a new perspective on treating malignant ascites secondary to HCC.

Effect of Transarterial Chemotherapy on the Structure and Function of Gut Microbiota in New Zealand White Rabbits.

The gut microbiota (GM) are closely related to hepatocellular carcinoma (HCC) occurrence and development. Furthermore, patients with HCC who have received transcatheter arterial chemoembolization (TACE) treatment often experience adverse gastrointestinal reactions, which may be related to changes in the GM caused by the chemotherapeutic drugs used in TACE. Therefore, we conducted animal experiments to investigate these changes. We analyzed changes in the GM of New Zealand white rabbits treated with hepatic arterial chemotherapy by measuring the levels of serological and colonic tissue markers. Simultaneously, we evaluated the correlation between the GM and these markers to explore the mechanism by which chemotherapy affects the GM. Following transarterial chemotherapy with epirubicin, the Firmicutes abundance decreased, whereas that of Proteobacteria increased. The relative abundance of beneficial bacteria, such as Muribaculaceae, Enterococcus, Ruminococcus, and Clostridia, decreased in the experimental group compared with those in the control group. However, the relative abundance of harmful bacteria, such as Bacteroides and Escherichia (Shigella), was higher in the experimental group than in the control group. Following chemotherapy, the GM of rabbits showed a dynamic change over time, first aggravating and then subsiding. The changes were most notable on the fourth day after surgery and recovered slightly on the seventh day. The changes in the host's GM before and after arterial chemotherapy are evident. Hepatic arterial chemotherapy induces dysbiosis of the intestinal microbiota, disrupts intestinal barrier function, damages the integrity of the intestinal mucosa, increases intestinal permeability, facilitates excessive passage of harmful substances through the gut-liver axis communication between the liver and intestine, and triggers activation of inflammatory pathways such as LPS-TLR-4-pSTAT3, ultimately leading to an inflammatory response. This study provides a theoretical basis for combining TACE with targeted GM intervention to treat HCC and reduce adverse gastrointestinal reactions.

Research Progress of circRNAs during Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma

Hepatocellular carcinoma is prone to invasion and metastasis. It often receives a low diagnosis rate in the early stage but has an extremely high mortality rate. Epithelial-mesenchymal transformation (EMT) is a key factor in promoting tumor cell invasion and metastasis. Circular RNA (circRNA) is involved in regulating EMT in hepatocarcinoma cells through multiple pathways, thereby affecting the occurrence and progression of hepatocellular carcinoma. This article mainly reviews the research progress of circRNA related to EMT core transcription factors, circRNA that promotes EMT in liver cancer, and circRNA that inhibits EMT in liver cancer.

Early detection of nasopharyngeal carcinoma through machine-learning-driven prediction model in a population-based healthcare record database.

Early diagnosis and treatment of nasopharyngeal carcinoma (NPC) are vital for a better prognosis. Still, because of obscure anatomical sites and insidious symptoms, nearly 80% of patients with NPC are diagnosed at a late stage. This study aimed to validate a machine learning (ML) model utilizing symptom-related diagnoses and procedures in medical records to predict nasopharyngeal carcinoma (NPC) occurrence and reduce the prediagnostic period. Data from a population-based health insurance database (2001-2008) were analyzed, comparing adults with and without newly diagnosed NPC. Medical records from 90 to 360 days before diagnosis were examined. Five ML algorithms (Light Gradient Boosting Machine [LGB], eXtreme Gradient Boosting [XGB], Multivariate Adaptive Regression Splines [MARS], Random Forest [RF], and Logistics Regression [LG]) were evaluated for optimal early NPC detection. We further use a real-world data of 1 million individuals randomly selected for testing the final model. Model performance was assessed using AUROC. Shapley values identified significant contributing variables. LGB showed maximum predictive power using 14 features and 90 days before diagnosis. The LGB models achieved AUROC, specificity, and sensitivity were 0.83, 0.81, and 0.64 for the test dataset, respectively. The LGB-driven NPC predictive tool effectively differentiated patients into high-risk and low-risk groups (hazard ratio: 5.85; 95% CI: 4.75-7.21). The model-layering effect is valid. ML approaches using electronic medical records accurately predicted NPC occurrence. The risk prediction model serves as a low-cost digital screening tool, offering rapid medical decision support to shorten prediagnostic periods. Timely referral is crucial for high-risk patients identified by the model.

Impacts of glucagon-like peptide-1 receptor agonists on the risk of adverse liver outcomes in patients with metabolic dysfunction-associated steatotic liver disease cirrhosis and type 2 diabetes.

We examined the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) initiation on long-term Adverse Liver Outcomes (ALO) in patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) cirrhosis and type 2 diabetes using real-world data from the MarketScan database. We conducted a retrospective cohort study of patients with MASLD cirrhosis and type 2 diabetes between 2012 and 2020. Cox proportional hazard models examine the association between GLP-1RAs initiation, modelled as time-dependent, and the risk of ALO, a composite endpoint defined by the first occurrence of hepatic decompensation(s), portal hypertension, hepatocellular carcinoma (HCC) or liver transplantation (LT). We used Overlap Propensity Score Weighting (OPSW) to account for confounding. The study included 459 GLP-1RAs and 4837 non-GLP-1RAs patients. The non-GLP-1RAs patients presented with 1411 (29%) ALO over 7431.7 person years, while GLP-1RAs patients had 32 (7%) ALO over 586.6 person years - risk rate difference 13.5 (95% CI: 11.4-15.7) per 100 person-years. The OPSW-adjusted risk of ALO was reduced by 36% (hazard ratio [HR]: 0.64; 95% CI: 0.54-0.76) in patients with vs. without GLP-1RAs initiation. GLP-1RAs initiation was associated with significant reductions in the adjusted risk of hepatic decompensation (HR: 0.74; 95% CI: 0.61-0.88), portal hypertension (HR: 0.73; 95% CI: 0.60-0.88), HCC (HR: 0.37; 95% CI: 0.20-0.63) and LT (HR: 0.24; 95% CI: 0.12-0.43). The use of GLP-1RAs was associated with significant risk reductions in long-term adverse liver outcomes, including hepatic decompensation, portal hypertension, HCC and LT, in MASLD cirrhosis patients with type 2 diabetes.

Beneficial Effects of Traditional Chinese Medicine Fuzheng Huayu on the Occurrence of Hepatocellular Carcinoma in Patients with Compensated Chronic Hepatitis B Cirrhosis Receiving Entecavir: A Multicenter Retrospective Cohort Study.

The application of antifibrotic drugs to treat patients with chronic liver diseases who are receiving antiviral therapies for hepatocellular carcinoma (HCC) has not been established. Here, we aimed to assess the impact of the Traditional Chinese Medicine Fuzheng Huayu (FZHY) on the occurrence of HCC in patients with hepatitis B virus-related compensated cirrhosis receiving the antiviral drug entecavir (ETV). A multicenter retrospective cohort study was performed. Compensated liver cirrhosis patients were divided into the ETV+FZHY group or the ETV group according to treatment. The cumulative incidence of HCC was analyzed using Kaplan-Meier and log-rank tests. Propensity score matching was used for confounding factors. Stratified analysis and Cox regression were used to determine the effects of FZHY on the occurrence of HCC and liver function decompensation. Out of 910 chronic hepatitis B patients, 458 were in the ETV+FZHY group and 452 were in the ETV group. After propensity score matching, the 5-year cumulative incidence of HCC was 9.8% in the ETV+FZHY group and 21.8% in the ETV group (p<0.01). The adjusted hazard ratio for HCC was 0.216 (0.108, 0.432) when FZHY treatment was >36 months. Age, diabetes, alanine aminotransferase, γ-glutamyl transpeptidase, albumin, hepatitis B e-antigen, and fibrosis 4 score were associated with the occurrence of HCC. FZHY decreased the risk of HCC in patients aged >45 years with a hepatitis B virus DNA level of ≥2,000 IU/l. Adjunctive FZHY treatment reduced HCC occurrence in patients with hepatitis B virus cirrhosis who were treated with ETV, possibly due to the antifibrotic properties of FZHY.

Developing deep learning-based strategies to predict the risk of hepatocellular carcinoma among patients with nonalcoholic fatty liver disease from electronic health records

ObjectiveThe accuracy of deep learning models for many disease prediction problems is affected by time-varying covariates, rare incidence, covariate imbalance and delayed diagnosis when using structured electronic health records data. The situation is further exasperated when predicting the risk of one disease on condition of another disease, such as the hepatocellular carcinoma risk among patients with nonalcoholic fatty liver disease due to slow, chronic progression, the scarce of data with both disease conditions and the sex bias of the diseases. The goal of this study is to investigate the extent to which the aforementioned issues influence deep learning performance, and then devised strategies to tackle these challenges. These strategies were applied to improve hepatocellular carcinoma risk prediction among patients with nonalcoholic fatty liver disease. MethodsWe evaluated two representative deep learning models in the task of predicting the occurrence of hepatocellular carcinoma in a cohort of patients with nonalcoholic fatty liver disease (n = 220,838) from a national EHR database. The disease prediction task was carefully formulated as a classification problem while taking censorship and the length of follow-up into consideration. ResultsWe developed a novel backward masking scheme to deal with the issue of delayed diagnosis which is very common in EHR data analysis and evaluate how the length of longitudinal information after the index date affects disease prediction. We observed that modeling time-varying covariates improved the performance of the algorithms and transfer learning mitigated reduced performance caused by the lack of data. In addition, covariate imbalance, such as sex bias in data impaired performance. Deep learning models trained on one sex and evaluated in the other sex showed reduced performance, indicating the importance of assessing covariate imbalance while preparing data for model training. ConclusionsThe strategies developed in this work can significantly improve the performance of hepatocellular carcinoma risk prediction among patients with nonalcoholic fatty liver disease. Furthermore, our novel strategies can be generalized to apply to other disease risk predictions using structured electronic health records, especially for disease risks on condition of another disease.

Exploring the Role of PCDHGB4 in the Occurrence of Lung Squamous Cell Carcinoma Based on Bioinformatics Analysis

Lung squamous cell carcinoma (LUSC) is a subtypes of non-small cell lung cancer (NSCLC). It has been reported that members of the protocadherin γ family can regulate tumor cell growth by inhibiting the Wnt signaling pathway. Protocadherin-gamma subfamily B4 (PCDHGB4) as a family member in LUSC was rarely reported. The aim of this study was to investigate the role and potential prognostic value of PCDHGB4 in the development of LUSC using bioinformatics methods. The Cancer Genome Atlas (TCGA), cBioPortal and UALCAN databases were used to analyze the expression, prognosis, clinicopathological features, immune cell infiltration, immune regulatory genes, immune checkpoint inhibitors (ICIs), and methyltransferases of PCDHGB4 in LUSC. At the single cell level, we analyzed the clustering results of cell subtypes and the expression of PCDHGB4 in different immune cell subpopulations. In addition, we compared the promoter methylation levels of PCDHGB4 in LUSC tissues and normal tissues and performed protein-protein interaction and mutation analysis. Finally, enrichment analysis was performed based on the differentially expressed genes. Bioinformatics analysis results showed that the expression level of PCDHGB4 in LUSC tissues was lower than that in normal tissues. Survival analysis showed that increased PCDHGB4 expression was associated with poor prognosis. Single-cell sequencing analysis showed that PCDHGB4 was expressed in T cells, monocytes or macrophages, and dendritic cells. It was further found that PCDHGB4 played an important role in tumor immunity and confirmed that PCDHGB4 was associated with immune checkpoints, immune regulatory genes, and methyltransferases. Besides, enrichment analysis revealed that PCDHGB4 was involved in multiple cancer-related pathways. The expression of PCDHGB4 was low in LUSC. PCDHGB4 was related to the poor prognosis of patients, and PCDHGB4 was closely related to the infiltration and pathway of tumor immune cells. PCDHGB4 may be a potential prognostic marker and a new target for immunotherapy in LUSC.

Correlation of serum biomarker (LDH, CRP, IL-8) levels in pre-malignant and malignant lesions of head and neck

A precancerous lesion is often defined as morphologically altered tissue during which the occurrence of carcinoma is more likely than its normal counterpart. Head and neck cancers include cancers of the mouth and therefore the larynx, also as some rarer cancers like cancer of the sinuses, salivary glands, nose, and tympanic cavity. Head and neck cancers are often described as consistent with the sort of cell they begin with. A biomarker could be defined and interpreted as biological molecule which is mostly found in body fluids, blood or even tissues that indicates abnormalities of our body. Here we've taken three biomarkers (LDH, CRP, IL-8) to gauge their level rise in pre-malignant and malignant lesions which are present in our head and neck. Patients attending ENT OPD with primary symptoms indicating premalignant and malignant lesions in the region of head and neck had been included for the analytical study. Complete ENT examination followed by biopsy of the suspicious lesion and blood sample collection was done. A complete of 30 patients were included in each group of premalignant and malignant lesions. No mean serum rise of serum LDH was noted in premalignant and malignant lesions. A mean serum rise of serum CRP was noted in premalignant lesions but was not noted in malignant lesions. However, both premalignant and malignant lesions noted a mean serum rise of IL-8. From a future perspective serum evaluation of biomarkers can become a replacement diagnostic modality for the early evaluation of premalignant lesions and malignant lesions and for monitoring the prognosis of an equivalent.

Revealing distinct DNA methylation patterns in hepatic carcinoma through high-throughput sequencing

Abstract Objectives To study the relationship between DNA methylation and tumour development and provide experimental evidence for the personalized diagnosis and treatment of hepatic carcinoma. Methods The DNA of hepatic carcinoma tissue (Ca group) and adjacent normal tissue (T group) were extracted using the phenol-chloroform method and then treated with bisulfite. Twenty-five genes including 45 subtypes were amplified by PCR. The PCR products were sequenced via the Illumina 450k methylation array assay. The changes of methylated DNA performance were analysed through principal component analysis (PCA). Cluster analysis was used to evaluate the classification of methylated DNA regions. Haplotype abundance variation was tested for methylation differences. Statistical analysis was performed using the chi-square (χ2) test or Fisher’s exact test. Results Sequencing discoveries indicated CG-type methylation pervading all amplicons. However, CHG-type and CHH-type methylations were confined to only four amplicons (or nine subtypes). The methylation ratios of three specific amplicons (DAB2IP, PRDM14-1, Rab31-1) out of 45 amplicon subtypes in the Ca group significantly increased (over 10 %) compared to the T group (p&lt;0.05). Nineteen amplicons demonstrated minor distinction (methylation pattern variations between 1 and 10 %), with the remaining 23 amplicons showing only minimal disparities (under 1 %). PCA and cluster analysis unveiled a marked difference in methylation levels between cancerous and healthy tissues (p&lt;0.05). Conclusions The changes in haplotypes and methylation sites could serve as a biomarker for the clinical diagnosis of hepatic carcinoma. Methylation patterns might play an important role in the occurrence and development of hepatic carcinoma.

Liver Stiffness Values to Predict Occurrence and Recurrence of Hepatocellular Carcinoma.

Globally, liver cancer is the third most frequent etiology of cancer death, with the rates of occurrence of both new cases and mortality estimated to increase. Given the availability of multiple treatments, interdisciplinary management of the patient is crucial. Moreover, the diagnostic assessment of patients with severe liver fibrosis is essential for the staging of HCC and liver cirrhosis and early diagnosis of HCC. In this context, non-invasive evaluation plays a critical role in identifying prognostic factors of clinical application for the surveillance of the occurrence or recurrence of HCC. The new frontiers of transient elastography have become a useful tool to assess the risk of HCC occurrence and recurrence. There has been a major increase in studies investigating the cutoff liver stiffness value that best predicts the need for monitoring for the onset of HCC. Therefore, this review discusses the new advances that have occurred in the last four years on HCC, highlighting the new frontiers of non-invasive evaluation of HCC subjects, with particular attention regarding the clinical application of liver stiffness assessment for de novo HCC and predicting recurrence in patients with chronic HCV achieving sustained virological response after treatment with direct antiviral agents.

Carcinoma basocelular: incidencia y tendencias en Valencia (España)

BackgroundThere is a need for epidemiological and incidence data on the occurrence of basal cell carcinoma (BCC) in Spain. ObjectivesOur study was designed to retrospectively retrieve cases from our computer databases from 2010 through 2016 to provide updated data on the actual incidence of BCC in Valencia, eastern Spain. Material and methodsThis was an epidemiological study on basal cell carcinoma conducted in Valencia, eastern Spain. We analyzed a total of 2171 patients and 4047 tumors, and gathered data to estimate the actual incidence of BBC in our region. Results and conclusionsOur study confirmed that the incidence of BCC is much higher than previously reported. We calculated a crude incidence of 410.38 BCCs/100 000 person-years, an adjusted rate for the European population of 256.98 BCCs/100 000 person-years, and an adjusted rate for the world population of 196.26 BCCs/100 000 person-years. Risk is up to 29.49% higher for men (464.07 cases/100 000 person-years vs 358.40 cases/100 000 person-years for women). Incidence also increases by an annual 3.91% (a significantly higher annual incidence of 8.28% in women vs a 0.92% annual incidence in men). Overall, the lifetime risk for developing a BCC is 5.8% (5.02% in women and 7% in men).

Reduced Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Receiving Long-Term Besifovir Therapy.

No information is available regarding the influence of besifovir (BSV), a new nucleotide analogue, on the occurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study evaluated the reduced risk of HCC in patients undergoing BSV treatment. A total of 188 patients with CHB were treated with BSV for up to 8 years. We prospectively assessed the incidence of HCC compared with the risk from prediction models. During the follow-up, 5 patients developed HCC: 1 of 139 patients with non-cirrhotic CHB, and 4 of 49 patients with liver cirrhosis. We compared the HCC incidence in non-cirrhotic and cirrhotic patients with the predicted number derived from the REACH-B (risk estimation for HCC in CHB) model and GAG-HCC (guide with age, gender, HBV DNA, core promotor mutation, and cirrhosis) model, respectively. The standardized incidence ratio (SIR) was 0.128 (p = 0.039) at 7 years in non-cirrhotic CHB patients, and the SIR was 0.371 (p = 0.047) at 7.5 years in cirrhotic patients, suggesting a significantly decreased HCC incidence in both groups. HCC prediction was available for BSV-treated patients using existing models. In conclusion, BSV decreased the risk of HCC in patients with CHB, and prediction models were applicable. Clinical trial registry website and trial number: ClinicalTrials.gov no: NCT01937806.

Mechanism of intestinal microbiota disturbance promoting the occurrence and development of esophageal squamous cell carcinoma——based on microbiomics and metabolomics

Esophageal squamous cell carcinoma (ESCC) is a high-risk malignant tumor that has been reported in China. Some studies indicate that gut microbiota disorders can affect the occurrence and development of ESCC, but the underlying mechanism remains unclear. In this study, we aimed to explore the possible underlying mechanisms using microbiomics and metabolomics. Fifty ESCC patients and fifty healthy controls were selected as the study subjects according to sex and age, and fecal samples were collected. 16S rDNA sequencing and LC‒MS were used for microbiomics and nontargeted metabolomics analyses. We found significant differences in the composition of the gut microbiota and metabolites between the ESCC patients and control individuals (P < 0.05). ESCC patients exhibited increased abundances of Fusobacteriaceae and Lactobacillus, increased levels of GibberellinA34 and decreased levels of 12-hydroxydodecanoic acid; these metabolites could be diagnostic and predictive markers of ESCC. An increase in the abundance of Enterobacteriaceae and Lactobacillus significantly reduced the content of L-aspartate and pantothenic acid, which may be involved in the occurrence and development of ESCC by downregulating the expression of proteins in the pantothenate and coenzyme A biosynthesis pathways. An imbalance in the intestinal flora may decrease the number of eosinophils in peripheral blood, resulting in the activation of an inflammatory response and immune dysfunction, leading to ESCC deterioration. We hypothesize that this imbalance in the gut microbiota can cause an imbalance in intestinal metabolites, which can activate carcinogenic metabolic pathways, affect inflammation and immune function, and play a role in the occurrence and development of ESCC.

Increased matrix stiffness enhances pro-tumorigenic traits in a physiologically relevant breast tissue- monocyte 3D model

High mammographic density, associated with increased tissue stiffness, is a strong risk factor for breast cancer per se. In postmenopausal women there is no differences in the occurrence of ductal carcinoma in situ (DCIS) depending on breast density. Preliminary data suggest that dense breast tissue is associated with a pro-inflammatory microenvironment including infiltrating monocytes. However, the underlying mechanism(s) remains largely unknown. A major roadblock to understanding this risk factor is the lack of relevant in vitro models. A biologically relevant 3D model with tunable stiffness was developed by cross-linking hyaluronic acid. Breast cancer cells were cultured with and without freshly isolated human monocytes. In a unique clinical setting, extracellular proteins were sampled using microdialysis in situ from women with various breast densities. We show that tissue stiffness resembling high mammographic density increases the attachment of monocytes to the cancer cells, increase the expression of adhesion molecules and epithelia-mesenchymal-transition proteins in estrogen receptor (ER) positive breast cancer. Increased tissue stiffness results in increased secretion of similar pro-tumorigenic proteins as those found in human dense breast tissue including inflammatory cytokines, proteases, and growth factors. ER negative breast cancer cells were mostly unaffected suggesting that diverse cancer cell phenotypes may respond differently to tissue stiffness. We introduce a biological relevant model with tunable stiffness that resembles the densities found in normal breast tissue in women. The model will be key for further mechanistic studies. Additionally, our data revealed several pro-tumorigenic pathways that may be exploited for prevention and therapy against breast cancer. Statement of significanceWomen with mammographic high-density breasts have a 4–6-fold higher risk of breast cancer than low-density breasts. Biological mechanisms behind this increase are not fully understood and no preventive therapeutics are available. One major reason being a lack of suitable experimental models. Having such models available would greatly enhance the discovery of relevant targets for breast cancer prevention. We present a biologically relevant 3D-model for studies of human dense breasts, providing a platform for investigating both biophysical and biochemical properties that may affect cancer progression. This model will have a major scientific impact on studies for identification of novel targets for breast cancer prevention.

Cribriform-morular Thyroid Carcinoma Arising in a Medulloblastoma Survivor: Two Metachronous Tumors Shared with the Activation of the Wnt Signaling Pathway.

Wnt signaling pathway activation is involved in the pathogenesis of a series of malignant tumors and is characterized by the nuclear accumulation of β-catenin protein. The occurrence of two or more Wnt pathway-associated tumors in a single individual is uncommon and generally attributed to inherited cancer syndrome, especially familial adenomatous polyposis (FAP). Herein, we presented a rare case of a child who suffered from the occurrence of Wnt-activated medulloblastoma and cribriform-morular thyroid carcinoma (CMTC) within a 9-year interval. She had no history of FAP and harbored an unexpected somatic mutation of the APC gene in the CMTC tumor. The potential agents involved in the pathogenesis of the two molecular-linked tumors other than FAP were discussed in this report.

Application of metabolomics in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a prevalent malignancy affecting the head and neck region. The prognosis for OSCC patients remains unfavorable due to the absence of precise and efficient early diagnostic techniques. Metabolomics offers a promising approach for identifying distinct metabolites, thereby facilitating early detection and treatment of OSCC. This review aims to provide a comprehensive overview of recent advancements in metabolic marker identification for early OSCC diagnosis. Additionally, the clinical significance and potential applications of metabolic markers for the management of OSCC are discussed. This review summarizes metabolic changes during the occurrence and development of oral squamous cell carcinoma and reviews prospects for the clinical application of characteristic, differential metabolites in saliva, serum, and OSCC tissue. In this review, the application of metabolomic technology in OSCC research was summarized, and future research directions were proposed. Metabolomics, detection technology that is the closest to phenotype, can efficiently identify differential metabolites. Combined with statistical data analyses and artificial intelligence technology, it can rapidly screen characteristic biomarkers for early diagnosis, treatment, and prognosis evaluations.

LC-MS/MS method for the quantification of cortisol of hepatocellular carcinoma.

The imbalance of steroid hormones is closely related to the occurrence and development of hepatocellular carcinoma (HCC). However, most research has focused on steroid hormone receptors, and reports about the relationship between the serum concentration of cortisol and the development of HCC are rare. The aim of this research was to establish a simple, specific, sensitive and reliable liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method for the quantitation of cortisol in human serum and to compare the level of cortisol in serum between 221 HCC patients and 183 healthy volunteers. The results showed that the correlation coefficients of the linear regression with a weighing factor of 1/x2 ranged from 0.9933 to 0.9984 over the range of 2-1,000 ng/ml. The inter- and intra-day precision and accuracy were <10%. The matrix effect and recovery of cortisol were 94.9-102.5% and 96.3-99.8%, respectively. The concentration of cortisol in HCC patients was significantly higher than that in healthy volunteers (p < 0.05) and was not affected by sex, age, menopause or α-fetoprotein (AFP) level. The present study reveals that elevated cortisol might promote the progression of HCC.

The IGF2BP2-lncRNA TRPC7-AS1 axis promotes hepatocellular carcinoma cell proliferation and invasion

Hepatocellular carcinoma(HCC) is one of the most common tumors in the world. Human insulin-like growth factor 2(IGF2) mRNA binding protein 2(IGF2BP2) plays an important role in the progression of hepatocellular carcinoma. Additionally, long non-coding RNA(lncRNA) has been confirmed as a key regulator of hepatocellular carcinoma occurrence. However, the function of TRPC7-AS1 has not been verified in hepatocellular carcinoma. The research results revealed that high IGF2BP2 expression was associated with a decreased survival rate in patients with hepatocellular carcinoma. Furthermore, IGF2BP2 knockdown inhibited and IGF2BP2 overexpression promoted the cell proliferation and invasion of hepatocellular carcinoma cells. The research illuminated that IGF2BP2 regulated the expression of TRPC7-AS1, and a correlation was observed between IGF2BP2 and TRPC7-AS1 expression. TRPC7-AS1 silencing repressed and its overexpression promoted the progression of hepatocellular carcinoma. After silencing or overexpressing TRPC7-AS1, the expression of the high-mobility group AT-hook 2 (HMGA2) gene decreased or increased, respectively. IGF2BP2 enhanced the expression of TRPC7-AS1 and thus affected the expression of HMGA2, thereby promoting hepatocellular carcinoma progression.