Exploration of the Correlation Between GRHL1 Expression and Tumor Microenvironment in Endometrial Cancer and Immunotherapy.

Introduction: GRHL1 belongs to the family of Grainyhead-like (GRHL). Previous studies have shown that dysregulation of growth and survival pathways is associated with the GRHL family of gene cancers. Immunotherapy with checkpoint inhibitors has changed the treatment paradigm for many tumors, including endometrial cancer (EC). However, the effect of GRHL1 on immunotherapy in EC and its relationship with immune cell infiltration are poorly understood. Methods: Differential expression of GRHL1 between EC and normal EC tissues was analyzed by searching the TCGA database, and the results were verified utilizing immunohistochemistry analyses. Next, the relationship between GRHL1, CD8+ T cells and tumor microenvironment (TME) was also investigated, and the effect of GRHL1 expression on immunotherapy in EC was evaluated. Results: According to the findings, EC tissues had elevated expression levels of GRHL1 relative to normal tissues. Patients with EC who expressed GRHL1 at high levels experienced worse overall survival (OS) and Progression-free survival (PFS) than those whose expression was lower. In addition, GRHL1 expression was negatively correlated with CD8+ T cells, and patients with high GRHL1 expression were less effective in receiving immunotherapy. Conclusion: The expression of GRHL1 was high in EC patients, and high expression of GRHL1 inhibits the proliferation of CD8+ T cells in the tumor microenvironment of EC and affect the efficacy of immunotherapy.

Prognostic Model and Tumor Immune Microenvironment Analysis of Complement-Related Genes in Gastric Cancer.

Introduction: The complement system is integral to the innate and adaptive immune response, helping antibodies eliminate pathogens. However, the potential role of complement and its modulators in the tumor microenvironment (TME) of gastric cancer (GC) remains unclear. Methods: This study assessed the expression, frequency of somatic mutations, and copy number variations of complement family genes in GC derived from The Cancer Genome Atlas (TCGA). Lasso and Cox regression analyses were conducted to develop a prognostic model based on the complement genes family, with the training and validation sets taken from the TCGA-GC cohort (n=371) and the International Gene Expression Omnibus (GEO) cohort (n=433), correspondingly. The nomogram assessment model was used to predict patient outcomes. Additionally, the link between immune checkpoints, immune cells, and the prognostic model was investigated. Results: In contrast to patients at low risk, those at high risk had a less favorable outcome. The prognostic model-derived risk score was shown to serve as a prognostic marker of GC independently, as per the multivariate Cox analysis. Nomogram assessment showed that the model had high reliability for predicting the survival of patients with GC in the 1, 3, 5 years. Additionally, the risk score was positively linked to the expression of immune checkpoints, notably CTLA4, LAG3, PDCD1, and CD274, according to an analysis of immune processes. The core gene C5aR1 in the prognostic model was found to be upregulated in GC tissues in contrast to adjoining normal tissues, and patients with elevated expressed levels of C5aR1 had lower 10-year overall survival (OS) rates. Conclusion: Our work reveals that complement genes are associated with the diversity and complexity of TME. The complement prognosis model help improves our understanding of TME infiltration characteristics and makes immunotherapeutic strategies more effective.

Receptor-interacting protein kinase 1 (RIPK1) regulates cervical cancer cells via NF-κB-TNF-α pathway: An in vitro study.

INTRODUCTION: Cervical cancer (CC) is associated with high morbidity and mortality rates in women. Members of the receptor-interacting protein kinase (RIPK) family are important regulators of inflammation and cell death. However, the characteristics, molecular functions, and expression mechanisms of RIPK1 in CC remain unclear. MATERIAL AND METHODS: To determine whether RIPK1 can be used for targeted therapy of CC, we assessed the clinical importance, biological function, and potential impact of RIPK1 in CC in 50 patients with CC. We utilized immunohistochemical staining, transfection, western blotting, cell counting kit-8 assay, colony formation assay, and wound healing assays among others, to elucidate the role of RIPK1 in CC. RESULTS: RIPK1 expression was higher in tumor tissues than in paracancerous tissues. Poor prognosis of CC was linked to RIPK1 upregulation. Furthermore, silencing RIPK1 significantly inhibited the proliferation, migration, and invasion of CC cells in vitro. We also established that RIPK1 increased cell migration, invasion, and multiplication by regulating nuclear factor kappa-B (NF-κB) and tumor necrosis factor (TNF). DISCUSSION: RIPK1 activates NF-κB and regulates TNF release to enhance the proliferation and spread of CC cells while suppressing their apoptosis. Therefore, RIPK1 plays a key role in the formation and progression of CC and is a potential target for CC treatment.

Exploring the Correlation Between GPR176, a Potential Target Gene of Gastric Cancer, and Immune Cell Infiltration.

Introduction: GPR176, an orphan G protein-coupled receptor (GPCR), is essential for the progression of gastrointestinal cancers. However, it is still unclear how GPR176 affects tumor immunity and patient prognosis in gastric cancer (GC). Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were searched in this investigation to assess the expression patterns of GPR176 in GC tissues and normal gastric mucosa. The findings were further verified using immunohistochemical tests and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). The Kaplan-Meier method, univariate logistic regression, and Cox regression were then used to investigate the relationship between GPR176 and clinical traits. Additionally, the potential correlation between GPR176, immune checkpoint genes, and immune cell infiltration levels was investigated. Results: As per the research findings, GC tissues had higher levels of GPR176 than normal tissues. Additionally, individuals with high expression of GPR176 had a worse 10-year overall survival (OS), in contrast with those having a low expression of GPR176 (p < 0.001). The OS of GC can be predicted using a validated nomogram model. The expression of GPR176 demonstrated a negative correlation with CD8+ T cells. When compared to the low-expression group of GPR176, Tumor Immune Dysfunction and Exclusion (TIDE) analysis demonstrated that the high-expression group had a considerably higher risk of immune evasion. A remarkable difference (variation) was observed in the levels of GPR176 expression across both groups, ie, low and high-risk groups, as determined by the immune phenomenon scores (IPS) immunotherapy assessment. Conclusion: By examining GPR176 from various biological perspectives, it was determined that GPR176 can act as a predictive biomarker for poor patient prognosis in GC. Additionally, it was observed that GPR176 is capable of suppressing the proliferation of CD8+ T cells and facilitating immune evasion.

Clinicopathological and prognosis significance of RIPK1 in patients with cervical squamous cell carcinoma: a retrospective cohort study.

Background: Cervical cancer is one of the most common types of carcinoma in women and has high morbidity and mortality rates worldwide. Recurrent and metastatic disease remains difficult to treat. Receptor interacting protein kinase 1 (RIPK1) is a key molecule in mediating apoptosis, necroptosis, and inflammatory pathways downstream of death receptors and pattern recognition receptors. This study sought to explore the clinicopathological and prognosis significance of RIPK1 expression in cervical squamous cell carcinoma (CSCC). Methods: The data of 100 CSCC patients who underwent curative surgery from 2019 to 2020 were retrospectively included in this study. We collected the clinicopathological information of the patients and detected RIPK1 protein expression using immunohistochemistry. The Chi-square test and a 1-way analysis of variance were used to make comparisons between groups stratified by RIPK1 expression. A Pearson linear correlation analysis was used to evaluate the association between RIPK1 expression and the clinicopathological characteristics of the patients. A Cox regression analysis and Kaplan-Meier curves were used to analyze overall survival (OS) and progression-free survival (PFS). A multivariable regression analysis was conducted to identify the risk factors for an impaired prognosis in CSCC. Results: RIPK1 was found to be overexpressed in the CSCC tissues. RIPK1 expression was significantly associated with age, the preoperative serum squamous cell carcinoma antigen (SCC-Ag) level, lymph node metastasis, invasion depth, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, PFS, and OS (P<0.05). The PFS and OS differed significantly among patients with RIPK1 expression (P<0.05). The multivariate analysis showed that RIPK1 was not independent risk factors for PFS and OS in CSCC patients (P>0.05). Conclusions: The expression of RIPK1 was significantly upregulated in CSCC and was associated with the clinicopathological features of CSCC. RIPK1 might serve as a novel marker that can be used to predict the prognosis of CSCC patients and as a biological target for the treatment of CSCC.

Exploring Prognosis, Tumor Microenvironment and Tumor Immune Infiltration in Hepatocellular Carcinoma Based on ATF/CREB Transcription Factor Family Gene-Related Model.

Introduction: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. It is the fourth leading cause of cancer-related death worldwide. Deregulation of the ATF/CREB family is associated with the progression of metabolic homeostasis and cancer. Because the liver plays a central role in metabolic homeostasis, it is critical to assess the predictive value of the ATF/CREB family in the diagnosis and prognosis of HCC. Methods: Using data from The Cancer Genome Atlas (TCGA), this research evaluated the expression, copy number variations, and frequency of somatic mutations of 21 genes in the ATF/CREB family in HCC. A prognostic model based on the ATF/CREB gene family was developed via Lasso and Cox regression analyses, with the TCGA cohort serving as the training dataset and the International Cancer Genome Consortium (ICGC) cohort serving as the validation set. Kaplan-Meier and receiver operating characteristic analyses verified the accuracy of the prognostic model. Furthermore, the association among the prognostic model, immune checkpoints, and immune cells was examined. Results: High-risk patients exhibited an unfavorable outcome as opposed to those in the low-risk category. Multivariate Cox analysis revealed that the risk score calculated based on the prognostic model was an independent prognostic factor for HCC. Analysis of immune mechanisms revealed that the risk score had a positive link to the expression of immune checkpoints, particularly CD274, PDCD1, LAG3, and CTLA4. Differences in immune cells and immune-associated roles were found between the high- and low-risk patients, as determined by single-sample gene set enrichment analysis. The core genes ATF1, CREB1, and CREB3 in the prognostic model were shown to be upregulated in HCC tissues as opposed to adjoining normal tissues, and the 10-year overall survival (OS) rate was worse among patients with elevated expression levels of ATF1, CREB1, and CREB3. Elevated expression levels of ATF1, CREB1, and CREB3 in HCC tissues were confirmed by qRT-PCR and immunohistochemistry studies. Conclusion: According to the results of our training set and test set, the risk model based on the six ATF/CREB gene signatures predicting prognosis has certain predictive accuracy in predicting the survival of HCC patients. This study provides novel insights into the individualized treatment of patients with HCC.

C5aR1 shapes a non-inflammatory tumor microenvironment and mediates immune evasion in gastric cancer.

C5a receptor 1 (C5aR1) is associated with various inflammatory processes, the pathogenesis of immune diseases, and tumor growth. However, its role in the tumor microenvironment of gastric cancer (GC) remains unclear. In this study, the expression of C5aR1 in GC and normal gastric mucosa tissues was compared using data retrieved from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, and the results were validated by in vitro qRT-PCR and immunohistochemical analyses. The relationship between C5aR1 expression and the overall survival of patients with GC was analyzed using the Kaplan-Meier method. Subsequently, enrichment analysis was performed, and the signaling pathways were screened. C5aR1 expression was also correlated with genes related to the immune checkpoint and immune cell infiltration. The results revealed that C5aR1 expression was enhanced in GC tissues compared to normal gastric tissues, and that patients with high expression of C5aR1 had a worse 10-year overall survival compared to those showing low expression of C5aR1. Functional analysis revealed that C5aR1 is a gene related to theimmune system and may play a crucial role in inflammatory and tumor immune responses. Additionally, C5aR1 showed a positive correlation with most immune checkpoint-related genes and a negative correlation with natural killer cells, dendritic cells, and CD8+ T cells. Immune evasion risk was observed to be significantly greater in patients with higher expression of C5aR1 than in those with lower expression. The results of this study reveal that C5aR1 shapes a non-inflammatory tumor microenvironment in GC and mediates immune evasion.

Endometrial cancer prognosis prediction using correlation models based on CDK family genes.

Cyclin-dependent kinases (CDKs) play an important role in cell division. Given that abnormal cell proliferation caused by dysregulation of cell division is one of the major causes of endometrial cancer (EC), it is important to elucidate the role of CDK family genes in the diagnosis and prognosis of EC. In this study, The Cancer Genome Atlas (TCGA) database was used to analyze the frequency of copy number variations and somatic mutations in 26 CDK family genes. Subsequently, the expression of these genes in EC was assessed, and their relationship with overall survival (OS) was examined via Kaplan-Meier analysis to assess their prognostic significance. A prognostic model based on seven CDK genes was constructed using Lasso and Cox regression, and the predictive performance of the model was analyzed using Kaplan-Meier analysis and column line plots. The correlation between CDK genes and immune cells was also examined. Patients with EC in the high-risk group had a poorer prognosis. The results of qRT-PCR and immunohistochemical analyses validated that CDK16 is highly expressed in EC tissues. Patients with EC with high CDK16 expression had worse 10-year OS than patients with low CDK16 expression. These findings suggest that the prognostic model constructed based on CDK genes can help to develop individualized and targeted treatment strategies for patients with EC.