Predictive Value and Immunological Role of the HSPA5 Gene in Cervical Cancer.

Cervical cancer (CC) ranks fourth among women's malignancies worldwide and seriously affects women's health. HSPA5 is a heat shock protein, also known as glucose regulatory protein 78 (GRP78). Upregulation of HSPA5 has been reported to be closely associated with multiple types of tumors. However, the specific role of HSPA5 in cervical cancer has not been discovered. In our study, we explored the prognostic value of HSPA5 in CC. Here, we analyzed the (TCGA) and (UCSC) databases, the analysis of HSPA5 in many tumors types was conducted with the "wilcox. test" method. A False Discovery Rate (FDR) value < 0.05 and Log2 | (fold change, FC) |> 1 were set as the cutoffs. "*", "**", and "***" indicate FDR < 0.05, < 0.01, and < 0.001, respectively, and further used human cervical cancer cells for q-PCR and western blotting detection. q-PCR and western blotting results showed that HSPA5 was highly expressed in cervical cancer cells, while it was expressed at low levels in normal cells (P < 0.05).We also analyzed the immunohistochemical data. immunohistochemical analysis results showed that HSPA5 was highly expressed in human cervical cancer, while it was expressed at low levels in normal tissues (P < 0.05). Analysis in TCGA-UCSC showed that the proportion of G3 in the group with high expression of HSPA5 was relatively high (P < 0.05). Enrichment analysis and survival analysis showed that the increased expression of HSPA5 in cervical cancer was related to the survival of CC and was involved in the regulation of biological behavior and molecular signaling pathways of cervical cancer. The correlation analysis of immune checkpoint and immune infiltration showed that HSPA5 was involved in the regulation of immune process of cervical cancer (P < 0.05). Drug sensitivity correlation analysis showed that HSPA5 was a sensitive target for tumor drugs (P < 0.05). In brief, those results suggest that HSPA5 can act as an oncogene of CC development and can serve as an effective predictive biomarker in cervical cancer.

Esophageal cancer screening, early detection and treatment: Current insights and future directions.

Esophageal cancer ranks among the most prevalent malignant tumors globally, primarily due to its highly aggressive nature and poor survival rates. According to the 2020 global cancer statistics, there were approximately 604000 new cases of esophageal cancer, resulting in 544000 deaths. The 5-year survival rate hovers around a mere 15%-25%. Notably, distinct variations exist in the risk factors associated with the two primary histological types, influencing their worldwide incidence and distribution. Squamous cell carcinoma displays a high incidence in specific regions, such as certain areas in China, where it meets the cost-effectiveness criteria for widespread endoscopy-based early diagnosis within the local population. Conversely, adenocarcinoma (EAC) represents the most common histological subtype of esophageal cancer in Europe and the United States. The role of early diagnosis in cases of EAC originating from Barrett's esophagus (BE) remains a subject of controversy. The effectiveness of early detection for EAC, particularly those arising from BE, continues to be a debated topic. The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses. In areas with higher incidences, such as China and Japan, early diagnosis is more common, which has led to the advancement of endoscopic methods as definitive treatments. These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality. Early screening, prompt diagnosis, and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.

Uncovering the flip side of immune checkpoint inhibitors: a comprehensive review of immune-related adverse events and predictive biomarkers.

Immune checkpoint inhibitors (ICIs) have generated considerable excitement as a novel class of immunotherapeutic agents due to their remarkable efficacy in treating various types of cancer. However, the widespread use of ICIs has brought about a number of safety concerns, especially the development of immune-related adverse events (irAEs). These serious complications could result in treatment discontinuation and even life-threatening consequences, making it critical to identify high-risk groups and predictive markers of irAEs before initiating therapy. To this end, the current article examines several potential predictive markers of irAEs in important organs affected by ICIs. While retrospective studies have yielded some promising results, limitations such as small sample sizes, variable patient populations, and specific cancer types and ICIs studied make it difficult to generalize the findings. Therefore, prospective cohort studies and real-world investigations are needed to validate the potential of different biomarkers in predicting irAEs risk. Overall, identifying predictive markers of irAEs is a crucial step towards improving patient safety and enhancing the management of irAEs. With ongoing research efforts, it is hoped that more accurate and reliable biomarkers will be identified and incorporated into clinical practice to guide treatment decisions and prevent the development of irAEs in susceptible patients.

Intestinal barrier in inflammatory bowel disease: A bibliometric analysis.

The primary objective of this investigation was to examine the evolving trajectories and pivotal focal points within the domain of research on intestinal barriers with regard to inflammatory bowel disease (IBD). Publications germane to the intestinal barrier in the context of IBD were procured from the Science Citation Index Expanded within the Web of Science Core Collection database. Bibliometric scrutiny and visualization were executed employing the R package "bibliometrix" through the R software platform (version: 4.3.0). A comprehensive compilation of 7344 English-language articles spanning from January 1, 2001 to December 31, 2021 was meticulously identified and included in the analysis. Remarkably, China emerged as the preeminent force in the realm of intestinal barrier research in relation to IBD. The significance of the intestinal barrier in the context of IBD has been progressively and comprehensively acknowledged. This recognition has ushered in a fresh therapeutic perspective that offers the promise of enhancing the management of inflammation and prognostication.

Angelica polysaccharides relieve blood glucose levels in diabetic KKAy mice possibly by modulating gut microbiota: an integrated gut microbiota and metabolism analysis.

BACKGROUND: Angelica polysaccharides (AP) have numerous benefits in relieving type 2 diabetes (T2D). However, the underlying mechanisms have yet to be fully understood. Recent many reports have suggested that altering gut microbiota can have adverse effects on the host metabolism and contribute to the development of T2D. Here, we successfully established the T2D model using the male KKAy mice with high-fat and high-sugar feed. Meanwhile, the male C57BL/6 mice were fed with a normal feed. T2D KKAy mice were fed either with or without AP supplementation. In each group, we measured the mice's fasting blood glucose, weight, and fasting serum insulin levels. We collected the cecum content of mice, the gut microbiota was analyzed by targeted full-length 16S rRNA metagenomic sequencing and metabolites were analyzed by untargeted-metabolomics. RESULTS: We found AP effectively alleviated glycemic disorders of T2D KKAy mice, with the changes in gut microbiota composition and function. Many bacteria species and metabolites were markedly changed in T2D KKAy mice and reversed by AP. Additionally, 16 altered metabolic pathways affected by AP were figured out by combining metagenomic pathway enrichment analysis and metabolic pathway enrichment analysis. The key metabolites in 16 metabolic pathways were significantly associated with the gut microbial alteration. Together, our findings showed that AP supplementation could attenuate the diabetic phenotype. Significant gut microbiota and gut metabolite changes were observed in the T2D KKAy mice and AP intervention. CONCLUSIONS: Administration of AP has been shown to improve the composition of intestinal microbiota in T2D KKAy mice, thus providing further evidence for the potential therapeutic application of AP in the treatment of T2D.

Copper in cancer: from limiting nutrient to therapeutic target.

As an essential nutrient, copper's redox properties are both beneficial and toxic to cells. Therefore, leveraging the characteristics of copper-dependent diseases or using copper toxicity to treat copper-sensitive diseases may offer new strategies for specific disease treatments. In particular, copper concentration is typically higher in cancer cells, making copper a critical limiting nutrient for cancer cell growth and proliferation. Hence, intervening in copper metabolism specific to cancer cells may become a potential tumor treatment strategy, directly impacting tumor growth and metastasis. In this review, we discuss the metabolism of copper in the body and summarize research progress on the role of copper in promoting tumor cell growth or inducing programmed cell death in tumor cells. Additionally, we elucidate the role of copper-related drugs in cancer treatment, intending to provide new perspectives for cancer treatment.

Single-cell RNA-seq and bulk RNA-seq explore the prognostic value of exhausted T cells in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains a worldwide health problem. Mounting evidence indicates that exhausted T cells play a critical role in the progress and treatment of HCC. Therefore, a detailed characterisation of exhausted T cells and their clinical significance warrants further investigation in HCC. Based on the GSE146115, we presented a comprehensive single-cell Atlas in HCC. Pseudo-time analysis revealed that tumour heterogeneity progressively increased, and the exhausted T cells gradually appeared during tumour progression. Functional enrichment analysis revealed that the evolutionary process of exhausted T cells mainly contained the pathway of cadherin binding, proteasome, cell cycle, and T cell receptor regulation of apoptosis. In the International Cancer Genome Consortium database, we divided patients into three clusters with the T cell evolution-associated genes. We found that the exhausted T cells are significantly related to poor outcomes through immunity and survival analysis. In The Cancer Genome Atlas database, the authors enrolled weighted gene co-expression network analysis, univariate Cox analysis, and Lasso Cox analysis, then screened the 19 core genes in T cells evolution and built a robust prognostic model. This study offers a fresh view on evaluating the patients' outcomes from an exhausted T cells perspective and might help clinicians develop therapeutic systems.

Prognostic and Immunological Significance of the Molecular Subtypes and Risk Signatures Based on Cuproptosis in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) remains a challenging medical problem. Cuproptosis is a novel form of cell death that plays a crucial role in tumorigenesis, angiogenesis, and metastasis. However, it remains unclear whether cuproptosis-related genes (CRGs) influence the outcomes and immune microenvironment of HCC patients. Method: From The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we obtained the mRNA expression file and related clinical information of HCC patients. We selected 19 CRGs as candidate genes for this study according to previous literature. We performed a differential expression analysis of the 19 CRGs between malignant and precancerous tissue. Based on the 19 CRGs, we enrolled cluster analysis to identify cuproptosis-related subtypes of HCC patients. A prognostic risk signature was created utilizing univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. We employed independent and stratification survival analyses to investigate the predictive value of this model. The functional enrichment features, mutation signatures, immune profile, and response to immunotherapy of HCC patients were also investigated according to the two molecular subtypes and the prognostic signature. Results: We found that 17 CRGs significantly differed in HCC versus normal samples. Cluster analysis showed two distinct molecular subtypes of cuproptosis. Cluster 1 is preferentially related to poor prognosis, high activity of immune response signaling, high mutant frequency of TP53, and distinct immune cell infiltration versus cluster 2. Through univariate and LASSO Cox regression analyses, we created a cuproptosis-related prognostic risk signature containing LIPT1, DLAT, MTF1, GLS, and CDKN2A. High-risk HCC patients were shown to have a worse prognosis. The risk signature was proved to be an independent predictor of prognosis in both the TCGA and ICGC datasets, according to multivariate analysis. The signature also performed well in different stratification of clinical features. The immune cells, which included regulatory T cells (Treg), B cells, macrophages, mast cells, NK cells, and aDCs, as well as immune functions containing cytolytic activity, MHC class I, and type II IFN response, were remarkably distinct between the high-risk and low-risk groups. The tumor immune dysfunction and exclusion (TIDE) score suggested that high-risk patients had a higher response rate to immune checkpoint inhibitors than low-risk patients. Conclusion: This research discovered the potential prognostic and immunological significance of cuproptosis in HCC, improved the understanding of cuproptosis, and may deliver new directions for developing more efficacious therapeutic techniques for HCC patients.

A bibliometric analysis of ferroptosis, necroptosis, pyroptosis, and cuproptosis in cancer from 2012 to 2022.

This study aims to visualize research hotspots and trends of "ferroptosis in cancer", "necroptosis in cancer", "pyroptosis in cancer", and "cuproptosis in cancer" through a bibliometric analysis to facilitate understanding of future developments in basic and clinical research and to provide a new perspective on cancer treatment. From January 1, 2012 to October 31, 2022, in the field of "ferroptosis in cancer", a total of 2467 organizations from 79 different countries published 3302 articles. 2274 organizations from 72 different countries published 2233 articles in the field of " necroptosis in cancer". 1366 institutions from 58 different countries contributed 1445 publications in the field of "pyroptosis in cancer". In the field of " cuproptosis in cancer", the number of articles published in the last 10 years is relatively low, with a total of 109 articles published by 116 institutions from four different countries. In the field of "ferroptosis in cancer", Tang Daolin had published 66 documents, ranked the first, while Dixon SJ is the most cited author, cited 3148 times; In the fields of "necroptosis in cancer", Vandenabeele peter had published 35 papers and Degterev had been cited 995 times, ranked the first, respectively; Kanneganti thirumala-devi had published 24 papers, is the highest number of publications in the fields of "pyroptosis in cancer", while Shi JJ was the most cited author with being cited 508 times. Both Huang Yan and Wang Tao published three papers and tied for first place and Tsvetkov p ranks first with being cited 107 times in "cuproptosis in cancer". "Cell", "Cell", "Nature", and "Science" was the most frequently co-cited journal on "ferroptosis in cancer", "necroptosis in cancer", "pyroptosis in cancer", and "cuproptosis in cancer", respectively. Further exploration of inhibitors of different Programmed cell death (PCD) and their targeted therapies are potential treatment options for cancer, but more direct clinical evidence as well as higher level clinical trials remain to be explored. Further clarification of the mechanisms of crosstalk between these PCDs may provide effective cancer treatments. And the role of different types of PCDs, especially the novel ones discovered, in cancer can be expected to remain a hot topic of research in the cancer field for quite some time to come.

Prognostic role of ring finger and WD repeat domain 3 and immune cell infiltration in hepatocellular carcinoma.

We have found that the expression of ring finger and WD repeat domain 3 (RFWD3) is significantly higher in unpaired and paired hepatocellular carcinoma (HCC) tissues than in normal tissues. Moreover, this expression has a significant correlation with the infiltration level of 14 immune cell types and when the detected RFWD3 expression levels were grouped as high and low, a prominent difference was revealed for overall survival, disease-specific survival, and progression-free interval. Through statistical analysis (univariate Cox), we were also able to identify RFWD3 as an independent prognostic element for HCC, with RFWD3 having an ability to accurately predict HCC prognosis (area under the curve of 0.863). Finally, we have generated prognostic nomograms for probabilities of 1-, 3- and 5-year overall survival in HCC via integrating the factors of age, pathologic stage, alpha-fetoprotein level, and RFWD3 expression.

Prognostic significance of epidermal growth factor receptor and programmed cell death-ligand 1 co-expression in esophageal squamous cell carcinoma.

Our study aimed to observe the correlation between epidermal growth factor receptor (EGFR) and programmed cell death-ligand 1 (PD-L1) expression and evaluate prognostic potential of their co-expression in esophageal squamous cell carcinoma (ESCC) patients. EGFR and PD-L1 expression were evaluated by immunohistochemical analysis. We revealed that there was a positive correlation between EGFR and PD-L1 expression in ESCC (P = 0.004). According to the positive relationship between EGFR and PD-L1, all patients were divided into four groups: EGFR (+)/PD-L1 (+), EGFR (+)/PD-L1 (-), EGFR (-)/PD-L1 (+), and EGFR (-)/PD-L1 (-). In 57 ESCC patients without surgery, we found that EGFR and PD-L1 co-expression were statistically correlated with a lower objective response rate (ORR) (p = 0.029), overall survival (OS) (p = 0.018) and progression-free survival (PFS) (p = 0.045) than those with one or none positive protein. Furthermore, PD-L1 expression has a significant positive correlation with infiltration level of 19 immune cells, EGFR expression was significantly correlated with infiltration level of 12 immune cells. The infiltration level of CD8 T cell and B cell were negatively correlated with EGFR expression. On the contrary with EGFR, the infiltration level of CD8 T cell, and B cell were positively correlated with PD-L1 expression. In conclusion, EGFR and PD-L1 co-expression could predict poor ORR and survival in ESCC without surgery, indicating a subset of patients who may benefit from a combination of targeted therapy against EGFR and PD-L1, which may expand the population benefiting from immunotherapy and reduce the occurrence of hyper progressive diseases.

Prognosis-related metabolic genes in the development of colorectal cancer progress and perspective.

Colorectal cancer (CRC) is one of the most commonplace malignant tumors in the world. The occurrence and development of CRC are involved in numerous events. Metabolic reprogramming is one of the hallmarks of cancer and is convoluted and associated with carcinogenesis. Lots of metabolic genes are involved in the occurrence and progression of CRC. Study methods combining tumor genomics and metabolomics are more likely to explore this field in depth. In this mini-review, we make the latest progress and future prospects into the different molecular mechanisms of seven prognosis-related metabolic genes, we screened out in previous research, involved in the occurrence and development of CRC.

Construction and Validation of a Protein-associated Prognostic Model for Gastrointestinal Cancer.

Background Gastrointestinal cancer (GIC) is a prevalent and lethal malignant tumor. It is obligatory to investigate innovative biomarkers for the diagnosis and prognosis. Proteins play a crucial role in regulating the occurrence and progression of GIC. However, the prognostic value of proteins is unclear in GIC. OBJECTIVE: This paper aims to identify the hub prognosis-related proteins (PAPs) and construct a prognosis model for GIC patients for clinical application. METHODS: Protein expression data of GIC was obtained from The Cancer Proteome Atlas (TCPA) and downloaded the clinicopathological data from The Cancer Genome Atlas database (TCGA). Besides, hub proteins were filtrated via univariate and multivariate Cox regression analysis. Moreover, survival analysis and nomogram were used to predict overall survival (OS). We used the calibration curves to assess the consistency of predictive and actual survival rates. The consistency index (C-index) was used to evaluate the prognostic ability of the predictive model. Furthermore, functional enrichment analysis and protein co-expression of PAPs were used to explore their roles in GIC. RESULTS: Finally, a prognosis model was conducted based on ten PAPs (CYCLIND1, DVL3, NCADHERIN, SYK, ANNEXIN VII, CD20, CMET, RB, TFRC, and PREX1). The risk score calculated by the model was an independent prognostic predictor. Compared with the high-risk subgroup, the low-risk subgroup had better OS. In the TCGA cohort, the area under the curve value of the receiver operating characteristic curve of the prognostic model was 0.692. The expression of proteins and risk score had a significant association with the clinicopathological characteristics of GIC. Besides, a nomogram based on GIC clinicopathological features and risk scores could properly predict the OS of individual GIC patients. The C-index is 0.71 in the TCGA cohort and 0.73 in the GEO cohort. CONCLUSION: The results indicate that the risk score is an independent prognostic biomarker and is related to the malignant clinical features of GIC patients. Besides, several PAPs associated with the survival and clinicopathological characteristics of GIC might be potential biomarkers for GIC diagnosis and treatment.