tRNA-derived small RNAs in human cancers: roles, mechanisms, and clinical application.

Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are a new type of non-coding RNAs (ncRNAs) produced by the specific cleavage of precursor or mature tRNAs. tsRNAs are involved in various basic biological processes such as epigenetic, transcriptional, post-transcriptional, and translation regulation, thereby affecting the occurrence and development of various human diseases, including cancers. Recent studies have shown that tsRNAs play an important role in tumorigenesis by regulating biological behaviors such as malignant proliferation, invasion and metastasis, angiogenesis, immune response, tumor resistance, and tumor metabolism reprogramming. These may be new potential targets for tumor treatment. Furthermore, tsRNAs can exist abundantly and stably in various bodily fluids (e.g., blood, serum, and urine) in the form of free or encapsulated extracellular vesicles, thereby affecting intercellular communication in the tumor microenvironment (TME). Meanwhile, their abnormal expression is closely related to the clinicopathological features of tumor patients, such as tumor staging, lymph node metastasis, and poor prognosis of tumor patients; thus, tsRNAs can be served as a novel type of liquid biopsy biomarker. This review summarizes the discovery, production, and expression of tsRNAs and analyzes their molecular mechanisms in tumor development and potential applications in tumor therapy, which may provide new strategies for early diagnosis and targeted therapy of tumors.

Exosomal non-coding RNAs in colorectal cancer metastasis.

Colorectal cancer (CRC) is a type of gastrointestinal cancer with high morbidity and mortality rates, and is often accompanied by distant metastases. Metastasis is a major cause of shortened survival time and poor treatment outcomes for patients with CRC. However, the molecular mechanisms underlying the metastasis of CRC remain unclear. Exosomes are a class of small extracellular vesicles that originate from almost all human cells and can transmit biological information (e.g., nucleic acids, lipids, proteins, and metabolites) from secretory cells to target recipient cells. Recent studies have revealed that non-coding RNAs (ncRNAs) can be released by exosomes into the tumour microenvironment or specific tissues, and play a pivotal role in tumorigenesis by regulating a series of key molecules or signalling pathways, particularly those involved in tumour metastasis. Exosomal ncRNAs have potential as novel therapeutic targets for CRC metastasis, and can also be used as liquid biopsy biomarkers because of their specificity and sensitivity. Therefore, further investigations into the biological function and clinical value of exosomal ncRNAs will be of great value for the prevention, early diagnosis, and treatment of CRC metastasis.

Prognostic value and therapeutic potential of IAP family in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) ranks as the eighth most prevalent malignancy globally and has the eighth greatest fatality rate when compared to all other forms of cancer. The inhibitor of apoptosis protein (IAP) family comprises a collection of apoptosis-negative modulators characterized by at least one single baculovirus IAP repeat (BIR) domain in its N-terminal region. While the involvement of the IAP family is associated with the initiation and progression of numerous tumours, its specific role in HNSCC remains poorly understood. Thus, this study aimed to comprehensively examine changes in gene expression, immunomodulatory effects, prognosis, and functional enrichment of HNSCC utilising bioinformatics analysis. Elevated levels of distinct IAP family members were observed to varying degrees in HNSCC, with high BIRC2 expression indicating a worse prognosis. Additionally, Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to probe the enrichment of gene expression and biological processes related to the IAP family in HNSCC. The infiltration levels of immune cells were shown to be strongly associated with the IAP gene expression, as determined by subsequent analysis. Hence, BIRC2 could be an effective immunotherapy target for HNSCC. Collectively, novel knowledge of the biological roles and prognostic implications of IAP family members in HNSCC is presented in this study.

Experimental prognostic model integrating N6-methyladenosine-related programmed cell death genes in colorectal cancer.

Colorectal cancer (CRC) intricacies, involving dysregulated cellular processes and programmed cell death (PCD), are explored in the context of N6-methyladenosine (m6A) RNA modification. Utilizing the TCGA-COADREAD/CRC cohort, 854 m6A-related PCD genes are identified, forming the basis for a robust 10-gene risk model (CDRS) established through LASSO Cox regression. qPCR experiments using CRC cell lines and fresh tissues was performed for validation. The CDRS served as an independent risk factor for CRC and showed significant associations with clinical features, molecular subtypes, and overall survival in multiple datasets. Moreover, CDRS surpasses other predictors, unveiling distinct genomic profiles, pathway activations, and associations with the tumor microenvironment. Notably, CDRS exhibits predictive potential for drug sensitivity, presenting a novel paradigm for CRC risk stratification and personalized treatment avenues.

Exosome derived from tumor-associated macrophages: biogenesis, functions, and therapeutic implications in human cancers.

Tumor-associated macrophages (TAMs), one of the most abundant immune cell types in the tumor microenvironment (TME), account for approximately 50% of the local hematopoietic cells. TAMs play an important role in tumorigenesis and tumor development through crosstalk between various immune cells and cytokines in the TME. Exosomes are small extracellular vesicles with a diameter of 50-150 nm, that can transfer biological information (e.g., proteins, nucleic acids, and lipids) from secretory cells to recipient cells through the circulatory system, thereby influencing the progression of various human diseases, including cancer. Recent studies have suggested that TAMs-derived exosomes play crucial roles in malignant cell proliferation, invasion, metastasis, angiogenesis, immune responses, drug resistance, and tumor metabolic reprogramming. TAMs-derived exosomes have the potential to be targeted for tumor therapy. In addition, the abnormal expression of non-coding RNAs and proteins in TAMs-derived exosomes is closely related to the clinicopathological features of patients with cancer, and these exosomes are expected to become new liquid biopsy markers for the early diagnosis, prognosis, and monitoring of tumors. In this review, we explored the role of TAMs-derived exosomes in tumorigenesis to provide new diagnostic biomarkers and therapeutic targets for cancer prevention.

Comprehensive analysis of prognostic value and immune infiltration of IAPs family in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality rates. The inhibitors of apoptosis (IAP) family act as oncogenes in various tumor types; however, their functions in HCC remain unclear. Here, we used integrated bioinformatics analysis and experimental verification to assess the expression and the prognostic and clinical value of the IAP family in HCC. Using the University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) and the Tumor Immune Estimation Resource (TIMER), we analyzed the expression profiles of IAP family members in HCC tissue, normal tissues, and in patients with different stages and grades of HCC. We further verified the expression level of BIRC2 in 25 HCC samples and matched adjacent normal tissues using quantitative real-time PCR (qRT-PCR), and analyzed its correlation with the marker gene of T-helper type 1 cells (Th1)-STAT1. Meanwhile, the association between BIRC2 and the immunotherapeutic response or immunomodulators was confirmed using the Biomarker Exploration of Solid Tumors (BEST) database. The results showed that NAIP, BIRC2, BIRC3, XIAP, BIRC5, and BIRC6 mRNAs were overexpressed in HCC. The clinical stages, pathological grades, and other clinicopathological features of HCC were closely related to the expression levels of the IAP family members, especially the BIRC2 and BIRC5, which were found to be potential prognostic biomarkers for HCC. Expression of the IAPs was strongly associated with immune cell infiltration. Based on the infiltrative status of various immune cells, HCC patients with high BIRC2 and BIRC5 expression demonstrated poor overall survival (OS) rates. In patients with HCC, BIRC2 expression was noticeably elevated. Concurrently, the expression levels of BIRC2 and STAT1 showed a favorable correlation. BEST database analysis revealed that BIRC2 was a negative predictor of responsiveness to anti-programmed cell death ligand 1 (PD-L1)/cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) inhibitor treatment in HCC, and BIRC2 mRNA expression levels were positively correlated with the expression levels of the immune checkpoint genes programmed cell death protein 1 (PD-1), PD-L1, and CTLA-4 in HCC. Consequently, the IAP family may play a role in carcinogenesis and cancer-immune system interactions in HCC. Our results demonstrate that IAP family members may be viable predictive biomarkers and therapeutic targets for HCC.

Immunological role and prognostic value of somatostatin receptor family members in colon adenocarcinoma.

Colon adenocarcinoma (COAD) is among the most prevalent cancers worldwide, ranking as the third most prevalent malignancy in incidence and mortality. The somatostatin receptor (SSTR) family comprises G-protein-coupled receptors (GPCRs), which couple to inhibitory G proteins (Gi and Go) upon binding to somatostatin (SST) analogs. GPCRs are involved in hormone release, neurotransmission, cell growth inhibition, and cancer suppression. However, their roles in COAD remain unclear. This study used bioinformatics to investigate the expression, prognosis, gene alterations, functional enrichment, and immunoregulatory effects of the SSTR family members in COAD. SSTR1-4 are differentially downregulated in COAD, and low SSTR2 expression indicates poor survival. Biological processes and gene expression enrichment of the SSTR family in COAD were further analyzed using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology. A strong correlation was observed between SSTR expression and immune cell infiltration. We also quantified SSTR2 expression in 25 COAD samples and adjacent normal tissues using quantitative real-time polymerase chain reaction. We analyzed its correlation with the dendritic cell-integrin subunit alpha X marker gene. The biomarker exploration of the solid tumors portal was used to confirm the correlation between SSTR2 with immunomodulators and immunotherapy responses. Our results identify SSTR2 as a promising target for COAD immunotherapy. Our findings provide new insights into the biological functions of the SSTR family and their implications for the prognosis of COAD.

Novel role of immune-related non-coding RNAs as potential biomarkers regulating tumour immunoresponse via MICA/NKG2D pathway.

Major histocompatibility complex class I related chain A (MICA) is an important and stress-induced ligand of the natural killer group 2 member D receptor (NKG2D) that is expressed in various tumour cells. Given that the MICA/NKG2D signalling system is critically embedded in the innate and adaptive immune responses, it is particularly involved in the surveillance of cancer and viral infections. Emerging evidence has revealed the important roles of non-coding RNAs (ncRNAs) including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in different cancer types. We searched for all relevant publications in the PubMed, Scopus and Web of Science database using the keywords ncRNA, MICA, NKG2D, cancer, and miRNAs. All relevant studies published from 2008 to the 2023 were retrieved and collated. Notably, we found that miRNAs can target to NKG2D mRNA and MICA mRNA 3'-untranslated regions (3'-UTR), leading to translation inhibition of NKG2D and MICA degradation. Several immune-related MICA/NKG2D pathways may be dysregulated in cancer with aberrant miRNA expressions. At the same time, the competitive endogenous RNA (ceRNA) hypothesis holds that circRNAs, lncRNAs, and mRNAs induce an abnormal MICA expression by directly targeting downstream miRNAs to mediate mRNA suppression in cancer. This review summarizes the novel mechanism of immune escape in the ncRNA-related MICA/NKG2D pathway mediated by NK cells and cancer cells. Moreover, we identified the miRNA-NKG2D, miRNA-MICA and circRNA/lncRNA/mRNA-miRNA-mRNA/MICA axis. Thus, we were particularly concerned with the regulation of mediated immune escape in the MICA/NKG2D pathway by ncRNAs as potential therapeutic targets and diagnostic biomarkers of immunity and cancer.

Integrative evaluation and experimental validation of the immune-modulating potential of dysregulated extracellular matrix genes in high-grade serous ovarian cancer prognosis.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is a challenging malignancy characterized by complex interactions between tumor cells and the surrounding microenvironment. Understanding the immune landscape of HGSOC, particularly the role of the extracellular matrix (ECM), is crucial for improving prognosis and guiding therapeutic interventions. METHODS AND RESULTS: Using univariate Cox regression analysis, we identified 71 ECM genes associated with prognosis in seven HGSOC populations. The ECMscore signature, consisting of 14 genes, was validated using Cox proportional hazards regression with a lasso penalty. Cox regression analyses demonstrated that ECMscore is an excellent indicator for prognostic classification in prevalent malignancies, including HGSOC. Moreover, patients with higher ECMscores exhibited more active stromal and carcinogenic activation pathways, including apical surface signaling, Notch signaling, apical junctions, Wnt signaling, epithelial-mesenchymal transition, TGF-beta signaling, and angiogenesis. In contrast, patients with relatively low ECMscores showed more active immune-related pathways, such as interferon alpha response, interferon-gamma response, and inflammatory response. The relationship between the ECMscore and genomic anomalies was further examined. Additionally, the correlation between ECMscore and immune microenvironment components and signals in HGSOC was examined in greater detail. Moreover, the expression of MGP, COL8A2, and PAPPA and its correlation with FAP were validated using qRT-PCR on samples from HGSOC. The utility of ECMscore in predicting the prospective clinical success of immunotherapy and its potential in guiding the selection of chemotherapeutic agents were also explored. Similar results were obtained from pan-cancer research. CONCLUSION: The comprehensive evaluation of the ECM may help identify immune activation and assist patients in HGSOC and even pan-cancer in receiving proper therapy.

The NT5DC family: expression profile and prognostic value in pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is a malignant tumor with high morbidity and mortality rates. The NT5DC family is an evolutionarily-conserved family of 5'-nucleosidases that catalyze the intracellular hydrolysis of nucleotides. Although the NT5DC family has been linked to the initiation and growth of several cancers, its function in PAAD remains unclear. A series of bioinformatic analyses was used to ascertain the expression, prognosis, gene changes, functional enrichment, and immune regulatory functions of the NT5DC family in PAAD. NT5C2 and NT5DC1/2 mRNA and protein levels are increased in PAAD. Furthermore, the high mRNA expressions of NT5C2, NT5DC2, and NT5DC4 indicate a poor prognosis in patients with PAAD. The enrichment of biological processes and gene expression in the NT5DC family in PAAD were investigated using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses. Further investigations into immune infiltration revealed a close relationship between NT5DC gene expression and immune cell infiltration. These findings provide new insights into the biological function and prognostic value of the NT5DC gene family in PAAD.

miR-18a expression correlates with ATM and p53 levels and poor prognosis in lymphomas.

microRNAs (miRNAs) are non-coding, endogenous, small-molecule RNAs. They are involved in cell proliferation, differentiation, apoptosis, and metabolism. Additionally, they play an essential role in the development and progression of various malignancies. Recent research has revealed that miR-18a plays an important role in cancer development. However, its role in lymphoma is not yet fully understood. In this study, we investigated the clinicopathological characteristics and potential functional roles of miR-18a in lymphomas. First, we predicted the potential downstream genes of miR-18a using miRTarBase software and subjected these downstream genes to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to determine the potential mechanisms of action of these genes. We found that these target genes were closely related to cellular senescence, the p53 signaling pathway, and other signaling pathways. From the predicted downstream target genes, ATM and p53 were selected as the target genes; their deletion in patients with lymphoma was detected using the fluorescence in situ hybridization technique. The results showed that some patients with lymphoma have a deletion of the ATM and p53 genes. In addition, the deletion rates of ATM and p53 were positively correlated with the expression of miR-18a. Next, the expression levels of miR-18a and the deletion rates of ATM and p53 were used for correlation and prognostic analyses with patient clinical information. The findings revealed a significant difference in disease-free survival (DFS) between patients with lymphoma with ATM deletion and those with a normal ATM gene expression (p < 0.001). Moreover, a significant difference in overall survival (OS) and DFS between patients with p53 deletion and those with normal p53 expression was observed (p < 0.001). The results indicate that the deletion of ATM and p53 downstream of miR-18a is closely associated with the development of lymphoma. Thus, these biomarkers may serve as key prognostic biomarkers for lymphomas.

Emerging role of ferroptosis-related circular RNA in tumor metastasis.

Tumor metastasis is an important factor that contributes to the poor prognosis of patients with tumors. Therefore, to solve this problem, research on the mechanism of metastasis is essential. Ferroptosis, a new mode of cell death, is characterized by membrane damage due to lipid peroxidation caused by iron overload. Many studies have shown that excessive ferroptosis can affect tumor metastasis and thus inhibit tumor progression. Recently, circular RNA (circRNA), a type of non-coding RNA, has been shown to be associated with the progression of ferroptosis, thus influencing tumor development. However, the specific mechanisms by which circRNAs affect the progression of ferroptosis and their roles in tumor metastasis are not known. In this review, we systematically discuss the role of circRNAs in regulating tumor ferroptosis and their mechanism of action through sponging miRNAS in various tumors, thereby impacting metastasis. This review helps elucidate the relationship and role of ferroptosis-related circRNAs in tumor metastasis and may provide future researchers with new ideas and directions for targeted therapies.

Crosstalk between N6-methyladenosine (m6A) modification and noncoding RNA in tumor microenvironment.

N6-methyladenosine (m6A) is the most abundant RNA modification in eukaryotes, and it participates in the regulation of pathophysiological processes in various diseases, including malignant tumors, by regulating the expression and function of both coding and non-coding RNAs (ncRNAs). More and more studies demonstrated that m6A modification regulates the production, stability, and degradation of ncRNAs and that ncRNAs also regulate the expression of m6A-related proteins. Tumor microenvironment (TME) refers to the internal and external environment of tumor cells, which is composed of numerous tumor stromal cells, immune cells, immune factors, and inflammatory factors that are closely related to tumors occurrence and development. Recent studies have suggested that crosstalk between m6A modifications and ncRNAs plays an important role in the biological regulation of TME. In this review, we summarized and analyzed the effects of m6A modification-associated ncRNAs on TME from various perspectives, including tumor proliferation, angiogenesis, invasion and metastasis, and immune escape. Herein, we showed that m6A-related ncRNAs can not only be expected to become detection markers of tumor tissue samples, but can also be wrapped into exosomes and secreted into body fluids, thus exhibiting potential as markers for liquid biopsy. This review provides a deeper understanding of the relationship between m6A-related ncRNAs and TME, which is of great significance to the development of a new strategy for precise tumor therapy.

lncRNA cytoskeleton regulator RNA (CYTOR): Diverse functions in metabolism, inflammation and tumorigenesis, and potential applications in precision oncology.

Long non-coding RNAs (lncRNAs) are a novel class of non-coding RNA (ncRNA), that have been studied extensively in the field of tumor research in recent years. In the case of tumor-associated lncRNAs, lncRNA cytoskeleton regulator RNA (CYTOR) displays extensive functions in tumorigenesis, including invasion, metastasis, malignant proliferation, glycolysis, and inflammatory response. Moreover, the dysregulation of CYTOR is closely related to clinicopathological characteristics, such as tumor stage, lymph node metastasis and infiltration, and poor prognosis of tumor patients. In this review, we provide a novel strategy to summarize the biological functions and clinical value of CYTOR in tumors through an overview of the literature combined with gene set enrichment analysis. A deeper understanding of the role of CYTOR in tumorigenesis may provide new diagnostic, prognostic and therapeutic markers for human tumors.

Efficient Therapy of Inflammatory Bowel Disease (IBD) with Highly Specific and Durable Targeted Ta2 C Modified with Chondroitin Sulfate (TACS).

Non-invasive localization of lesions and specific targeted therapy are still the main challenges for inflammatory bowel disease (IBD). Ta, as a medical metal element, has been widely used in the treatment of different diseases because of its excellent physicochemical properties but is still far from being explored in IBD. Here, Ta2 C modified with chondroitin sulfate (CS) (TACS) is evaluated as a highly targeted therapy nanomedicine for IBD. Specifically, TACS is modified with dual targeting CS functions due to IBD lesion-specific positive charges and high expression of CD44 receptors. Thanks to the acid stability, sensitive CT imaging function, and strong reactive oxygen species (ROS) elimination ability, oral TACS can accurately locate and delineate IBD lesions through non-invasive CT imaging, and specifically targeted treat IBD effectively because high levels of ROS are a central factor in the progression of IBD. As expected, TACS has much better imaging and therapeutic effects than clinical CT contrast agent and first-line drug 5-aminosalicylic acid, respectively. The mechanism of TACS treatment mainly involves protection of mitochondria, elimination of oxidative stress, inhibiting macrophage M1 polarization, protection of intestinal barrier, and restoration of intestinal flora balance. Collectively, this work provides unprecedented opportunities for oral nanomedicines to targeted therapy of IBD.

Prognostic value of sirtuin family members and experimental verification identify SIRT5 as diagnostic biomarkers in clear cell renal cell carcinoma.

Background: The sirtuins (SIRTs) family is a nicotinamide adenine dinucleotide (NAD+) family of dependent deacetylases, which includes SIRT1-7. This family is related to the development and progression of various tumors. However, a comprehensive analysis of the role of SIRTs in clear cell renal cell carcinoma (ccRCC) is still lacking, and there are few reports on the inhibitory role of SIRT5 in ccRCC. Methods: We used immunohistochemical analysis, and several bioinformatic databases to perform an integrated analysis of the expression and prognostic value of SIRT5 and other SIRT family members in ccRCC along with the associated immune cell infiltration. These databases include TIMER, THPA, cell culture, UALCAN, cBioPortal, WebGestalt, Metascape, DiseaseMeth, STRING database, and Cytoscape. Results: The protein expression of SIRT1, 2, 3, 6, and 7 were upregulated in ccRCC for the Human Protein Atlas database, whereas the expression of SIRT4 and SIRT5 was decreased. The expression based on tumor stage, and grade followed a similar trend. Kaplan-Meier analysis showed that high SIRT4 and SIRT5 expression was positively related to better overall survival (OS), whereas SIRT6 and SIRT7 expression was positively related to worse OS. Further, high SIRT3 expression was related to worse relapse-free survival (RFS), whereas high SIRT5 expression was related to better RFS. To explore the mechanism underlying the function of SIRTs in ccRCC, we also used several databases to perform the functional enrichment analysis and explore the relationship between infiltrating immune cells and seven SIRT family members in ccRCC. The results showed that several SIRT family members, and particularly SIRT5, are correlated with the infiltration of some important immune cells. The protein expression of SIRT5 was significantly lower in tumor tissue compared to normal tissue and was negatively related to the age of the patient ccRCC individual tumor stages, and grades. In human ccRCC samples, strong IHC staining expression of SIRT5 was displayed in adjacent normal tissue than in tumor tissues. Conclusion: SIRT5 may be a prognostic marker and a novel strategy for the treatment of ccRCC.

Machine learning-based integration develops an immune-related risk model for predicting prognosis of high-grade serous ovarian cancer and providing therapeutic strategies.

Background: High-grade serous ovarian cancer (HGSOC) is a highly lethal gynecological cancer that requires accurate prognostic models and personalized treatment strategies. The tumor microenvironment (TME) is crucial for disease progression and treatment. Machine learning-based integration is a powerful tool for identifying predictive biomarkers and developing prognostic models. Hence, an immune-related risk model developed using machine learning-based integration could improve prognostic prediction and guide personalized treatment for HGSOC. Methods: During the bioinformatic study in HGSOC, we performed (i) consensus clustering to identify immune subtypes based on signatures of immune and stromal cells, (ii) differentially expressed genes and univariate Cox regression analysis to derive TME- and prognosis-related genes, (iii) machine learning-based procedures constructed by ten independent machine learning algorithms to screen and construct a TME-related risk score (TMErisk), and (iv) evaluation of the effect of TMErisk on the deconstruction of TME, indication of genomic instability, and guidance of immunotherapy and chemotherapy. Results: We identified two different immune microenvironment phenotypes and a robust and clinically practicable prognostic scoring system. TMErisk demonstrated superior performance over most clinical features and other published signatures in predicting HGSOC prognosis across cohorts. The low TMErisk group with a notably favorable prognosis was characterized by BRCA1 mutation, activation of immunity, and a better immune response. Conversely, the high TMErisk group was significantly associated with C-X-C motif chemokine ligands deletion and carcinogenic activation pathways. Additionally, low TMErisk group patients were more responsive to eleven candidate agents. Conclusion: Our study developed a novel immune-related risk model that predicts the prognosis of ovarian cancer patients using machine learning-based integration. Additionally, the study not only depicts the diversity of cell components in the TME of HGSOC but also guides the development of potential therapeutic techniques for addressing tumor immunosuppression and enhancing the response to cancer therapy.

Deciphering comprehensive features of tumor microenvironment controlled by chromatin regulators to predict prognosis and guide therapies in uterine corpus endometrial carcinoma.

Background: Dysregulation of chromatin regulators (CRs) can perturb the tumor immune microenvironment, but the underlying mechanism remains unclear. We focused on uterine corpus endometrial carcinoma (UCEC) and used gene expression data from TCGA-UCEC to investigate this mechanism. Methods: We used weighted gene co-expression network analysis (WGCNA) and consensus clustering algorithm to classify UCEC patients into Cluster_L and Cluster_H. TME-associated CRs were identified using WGCNA and differential gene expression analysis. A CR risk score (CRRS) was constructed using univariate Cox and LASSO-Cox regression analyses. A nomogram was developed based on CRRS and clinicopathologic factors to predict patients' prognosis. Results: Lower CRRS was associated with lower grade, more benign molecular subtypes, and improved survival. Patients with low CRRS showed abundant immune infiltration, a higher mutation burden, fewer CNVs, and better response to immunotherapy. Moreover, low CRRS patients were more sensitive to 24 chemotherapeutic agents. Conclusion: A comprehensive assessment of CRRS could identify immune activation and improve the efficacy of UCEC treatments.

Expression profile and prognostic values of GATA family members in kidney renal clear cell carcinoma.

To investigate the possible diagnostic and prognostic biomarkers of kidney renal clear cell carcinoma (KIRC), an integrated study of accumulated data was conducted to obtain more reliable information and more feasible measures. Using the Tumor Immune Estimation Resource (TIMER), University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN), Human Protein Atlas (HPA), Kaplan-Meier plotter database, Gene Expression Profiling Interactive Analysis (GEPIA2) database, cBioPortal, and Metascape, we analyzed the expression profiles and prognoses of six members of the GATA family in patients with KIRC. Compared to normal samples, KIRC samples showed significantly lower GATA2/3/6 mRNA and protein expression levels. KIRC's pathological grades, clinical stages, and lymph node metastases were closely related to GATA2 and GATA5 levels. Patients with KIRC and high GATA2 and GATA5 expression had better overall survival (OS) and recurrence-free survival (RFS), while those with higher expression of GATA3/4/6 had worse outcomes. The role and underlying mechanisms of the GATA family in cell cycle, cell proliferation, metabolic processes, and other aspects were evaluated based on Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses. Furthermore, we found that infiltrating immune cells were highly correlated with GATA expression profiles. These results showed that GATA family members may serve as prognostic biomarkers and therapeutic targets for KIRC.