FAT1 as a tumor mutation burden specific gene affects the immunotherapy effect in head and neck squamous cell cancer.

BACKGROUND: Response to immunotherapy is the main challenge of head and neck squamous cancer (HNSCC) treatment. Previous studies have indicated that tumor mutational burden (TMB) is associated with prognosis, but it is not always a precise index. Hence, investigating specific genetic mutations and tumor microenvironment (TME) changes in TMB-high patients is essential for precision therapy of HNSCC. METHODS: A total of 33 HNSCC patients were enrolled in this study. We calculated the TMB score based on next-generation sequencing (NGS) sequencing and grouped these patients based on TMB score. Then, we examined the immune microenvironment of HNSCC using assessments of the bulk transcriptome and the single-cell RNA sequence (scRNA-seq) focusing on the molecular nature of TMB and mutations in HNSCC from our cohort. The association of the mutation pattern and TMB was analyzed in The Cancer Genome Atlas (TCGA) and validated by our cohort. RESULTS: 33 HNSCC patients were divided into three groups (TMB-low, -medium, and -high) based on TMB score. In the result of 520-gene panel sequencing data, we found that FAT1 and LRP1B mutations were highly prevalent in TMB-high patients. FAT1 mutations are associated with resistance to immunotherapy in HNSCC patients. This involves many metabolism-related pathways like RERE, AIRE, HOMER1, etc. In the scRNA-seq data, regulatory T cells (Tregs), monocytes, and DCs were found mainly enriched in TMB-high samples. CONCLUSION: Our analysis unraveled the FAT1 gene as an assistant predictor when we use TMB as a biomarker of drug resistance in HNSCC. Tregs, monocytes, and dendritic cells (DCs) were found mainly enriched in TMB-high samples.

Next-generation sequencing identified that RET variation associates with lymph node metastasis and the immune microenvironment in thyroid papillary carcinoma.

BACKGROUND: To date, although most thyroid carcinoma (THCA) achieves an excellent prognosis, some patients experience a rapid progression episode, even with differentiated THCA. Nodal metastasis is an unfavorable predictor. Exploring the underlying mechanism may bring a deep insight into THCA. METHODS: A total of 108 THCA from Chinese patients with next-generation sequencing (NGS) were recruited. It was used to explore the gene alteration spectrum of THCA and identify gene alterations related to nodal metastasis in papillary thyroid carcinoma (PTC). The Cancer Genome Atlas THCA cohort was further studied to elucidate the relationship between specific gene alterations and tumor microenvironment. A pathway enrichment analysis was used to explore the underlying mechanism. RESULTS: Gene alteration was frequent in THCA. BRAF, RET, POLE, ATM, and BRCA1 were the five most common altered genes. RET variation was positively related to nodal metastasis in PTC. RET variation is associated with immune cell infiltration levels, including CD8 naïve, CD4 T and CD8 T cells, etc. Moreover, Step 3 and Step 4 of the cancer immunity cycle (CIC) were activated, whereas Step 6 was suppressed in PTC with RET variation. A pathway enrichment analysis showed that RET variation was associated with several immune-related pathways. CONCLUSION: RET variation is positively related to nodal metastasis in Chinese PTC, and anti-tumor immune response may play a role in nodal metastasis triggered by RET variation.

Multiple Functional Bonds Integrated Interphases for Long Cycle Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) have garnered significant interest as one of the most promising energy suppliers for power grid energy storage. However, the poor electrode/electrolyte interfacial stability leads to continual electrolyte decomposition and transition metal dissolution, resulting in rapid performance degradation of SIBs. In this work, we propose a strategy integrating multiple functional bonds to regulate electrode/electrolyte interphase by triple-coupling of succinonitrile (SN), sodium hexafluorophosphate (NaPF6) and fluorinated ethylene carbonate (FEC). Theoretical calculation and experiment results show that the solvation structure of Na+ and ClO4- is effectively reconfigured by the solvated FEC, SN and PF6- in PC-based carbonate electrolyte. The newly developed electrolyte demonstrates increased Na+-FEC coordination, weakened interaction of Na+-PC and participation of SN and PF6- anions in solvation, resulting in the formation of a conformal interfacial layer comprising of sodium oxynitrides (NaNxOy), sodium fluoride (NaF) and phosphorus oxide compounds (NaPxOy). Consequently, a 3 Ah pouch full cell of hard carbon//NaNi1/3Fe1/3Mn1/3O2 exhibits an excellent capacity retention of 90.4% after 1000 cycles. Detailed postmortem analysis of interface chemistry is further illustrated by multiple characterization methods. This study provides a new avenue for developing electrolyte formulations with multiple functional bonds integrated interphases to significantly improve the long-term cycling stability of SIBs.

Relativistic-guided stable mode of few-cycle 20 µm level infrared radiation.

The generation of intense infrared radiation with a wavelength greater than 10 µm is limited by the optical materials in traditional methods or the laser-plasma parameters of plasma-bubble methods. In this study, we propose a new method for generating an intense longitudinal radiation field of tens of GV/m. By utilizing the oscillations of the electron film on the inner surface of the micro-tube, excited by the relativistic electron beam propagating within it, it is possible to obtain tunable long-wavelength few-cycle infrared radiation, ranging from 20 to 30 µm and even longer. The radiation source is guided entirely by a relativistic electron beam and formed a stable TM propagation mode in the micro-tube. This opens up new opportunities for applications of the relativistic intensity infrared radiation to high-field physics, shorter attosecond pulses generation and charged particle acceleration.

Activation of bivalent factor DLX5 cooperates with master regulator TP63 to promote squamous cell carcinoma.

To reconstruct systematically hyperactive transcription factor (TF)-dependent transcription networks in squamous cell carcinomas (SCCs), a computational method (ELMER) was applied to 1293 pan-SCC patient samples, and 44 hyperactive SCC TFs were identified. As a top candidate, DLX5 exhibits a notable bifurcate re-configuration of its bivalent promoter in cancer. Specifically, DLX5 maintains a bivalent state in normal tissues; its promoter is hypermethylation, leading to DLX5 transcriptional silencing in esophageal adenocarcinoma (EAC). In stark contrast, DLX5 promoter gains active histone marks and becomes transcriptionally activated in ESCC, which is directly mediated by SOX2. Functionally, silencing of DLX5 substantially inhibits SCC viability both in vitro and in vivo. Mechanistically, DLX5 cooperates with TP63 in regulating ∼2000 enhancers and promoters, which converge on activating cancer-promoting pathways. Together, our data establish a novel and strong SCC-promoting factor and elucidate a new epigenomic mechanism - bifurcate chromatin re-configuration - during cancer development.

Risk factors for hemodynamic instability during laparoscopic resection of pheochromocytoma.

BACKGROUND: Laparoscopic adrenalectomy for pheochromocytoma is associated with high risk of intraoperative hemodynamic instability. Our study aimed to identify predictive factors for hemodynamic instability during laparoscopic resection of pheochromocytoma. METHODS: Between January 2011 and December 2021, 136 patients underwent unilateral laparoscopic adrenalectomy for pheochromocytoma. The patients were divided into 2 groups depending on the presence or absence of hemodynamic instability during surgery. Intraoperative hemodynamic parameters were compared between the 2 groups. Patient demographic characteristics and preoperative evaluations were assessed for their prognostic relevance with respect to intraoperative hemodynamic instability via both univariate analysis and multivariate logistic regression analysis. RESULTS: There was greater blood pressure fluctuations and higher maximum blood pressure and heart rate in the hemodynamic instability group. More patients need intraoperative administration of vasoactive drugs in the hemodynamic instability group. In the univariate analysis, presence of coronary artery disease, tumour size, and previous hypertension history were significantly associated with intraoperative hemodynamic instability. The multivariate logistic regression analysis showed that tumour size and previous hypertension history were independent risk factors for intraoperative hemodynamic instability. CONCLUSION: Tumour size and previous hypertension history were associated with hemodynamic instability during laparoscopic resection of pheochromocytoma.

Construction and validation of a prognostic model of RNA binding proteins in clear cell renal carcinoma.

BACKGROUND: The dysfunction of RNA binding proteins (RBPs) is associated with various inflammation and cancer. The occurrence and progression of tumors are closely related to the abnormal expression of RBPs. There are few studies on RBPs in clear cell renal carcinoma (ccRCC), which allows us to explore the role of RBPs in ccRCC. METHODS: We obtained the gene expression data and clinical data of ccRCC from the Cancer Genome Atlas (TCGA) database and extracted all the information of RBPs. We performed differential expression analysis of RBPs. Risk model were constructed based on the differentially expressed RBPs (DERBPs). The expression levels of model markers were examined by reverse transcription-quantitative PCR (RT-qPCR) and analyzed for model-clinical relevance. Finally, we mapped the model's nomograms to predict the 1, 3 and 5-year survival rates for ccRCC patients. RESULTS: The results showed that the five-year survival rate for the high-risk group was 40.2% (95% CI = 0.313 ~ 0.518), while the five-year survival rate for the low-risk group was 84.3% (95% CI = 0.767 ~ 0.926). The ROC curves (AUC = 0.748) also showed that our model had stable predictive power. Further RT-qPCR results were in accordance with our analysis (p < 0.05). The results of the independent prognostic analysis showed that the model could be an independent prognostic factor for ccRCC. The results of the correlation analysis also demonstrated the good predictive ability of the model. CONCLUSION: In summary, the 4-RBPs (EZH2, RPL22L1, RNASE2, U2AF1L4) risk model could be used as a prognostic indicator of ccRCC. Our study provides a possibility for predicting the survival of ccRCC.

TMEM196 hypermethylation as a novel diagnostic and prognostic biomarker for lung cancer.

Emerging evidences have revealed tumor-specific gene methylation is considered to be a promising non-invasive biomarker for many different types of cancers. This study was determined whether TMEM196 gene hypermethylation and downregulation are considered to be promising biomarkers for early diagnosis and prognosis in lung cancer. Methylation status was detected with methylation-specific PCR. Kaplan-Meier survival curves and Cox regression analysis were used to determine the significance of prognosis. TMEM196 gene was hypermethylated in 68.1% (64/94) of lung cancer tissues, 52.8% (67/127) of plasma and 55.2% (79/143) of sputum samples, but unmethylated (0/50) in normal tissues. TMEM196 methylation in plasma and sputum samples was significantly correlated with that in the corresponding paired tumor tissues (r = 0.750, r = 0.880, P < 0.001). TMEM196 aberrant methylation in cancer tissues, plasma and sputum DNA was significantly associated with age and pathological type (P < 0.05). TMEM196 high methylation could robustly distinguish lung cancer patients (AUC = 0.905) from normal subjects and patients with TMEM196 high methylation have a significantly poorer survival than those with low level from The Cancer Genome Atlas (Wilcoxon P < 0.001). Multivariate models showed TMEM196 methylation is an independent prognostic marker in lung cancer. Furthermore, the overall survival of patients with low TMEM196 expression was significantly poorer than that of TMEM196-high patients (P < 0.001, log-rank test). Low TMEM196 expression in tumor tissues was found to predict poorer survival (HR = 3.007; 95%CI, 1.918-4.714). Our study provided new insights into the clinical importance and potential use of TMEM196 methylation and expression as novel early diagnostic and prognostic biomarkers for human lung cancers.

Spatiotemporal Rule of Heat Transfer on a Soil/Finned Tube Interface.

To efficiently harvest environmental micro-energy from shallow soil, simulated analysis, theoretical arithmetic and experimental verification are performed to explore the spatiotemporal rules of heat transfer on a soil/finned tube interface. Simulations are carried out for 36 types of different working conditions, and the empirical formulas for temperature and heat flux are obtained. The temperature and heat flux can be calculated using the formulas if the soil temperature, soil moisture content and finned tube initial temperature are known. The simulations also show that the highest heat flux can reach approximately 0.30 mW/mm², and approximately 1507.96 mW of energy can be harvested through the finned tube. Theoretical arithmetic indicates that the heat transfer rate of the copper finned tube is 76.77% higher than that of the bare tube, the highest rate obtained in any study to date. Results also show that the finned tube should be placed where the soil moisture is greater than 30% to get more heat from the soil. A field experiment is carried out in the city of Harbin in Northeast China, where a thermoelectric power generation device has been installed and temperature data have been monitored for a certain time. The results are in good agreement with those obtained from the simulation analysis. The heat transfer processes and heat transfer steady state on the soil/finned tube interface are revealed in this work and are of great importance for the use of geothermal energy.

Neutrophil-to-Lymphocyte Ratio Predicts the Severity of Incarcerated Groin Hernia.

BACKGROUND The incarceration of a segment of bowel within a groin hernia can result in intestinal strangulation if hernia treatment is delayed. Once intestinal strangulation occurs, a bowel resection may be required, and there is an overall increased risk for postoperative complications. The aim of this study was to identify biomarkers to predict the severity of an incarcerated groin hernia. MATERIAL AND METHODS We retrospectively evaluated the records of 95 patients with incarcerated groin hernias who underwent emergency surgical correction of the hernias. The need for a bowel resection was regarded as an indicator of severity in incarcerated groin hernia patients. The patients were divided into 2 groups: patients with bowel resection surgery and patients without bowel resection surgery. RESULTS We discovered that leukocyte count (leukocyte count ≥10×10³/mm³), neutrophil-to-lymphocyte ratio (NLR, NLR ≥11.5), presentation of bowel obstruction, and duration of incarceration (duration of incarceration ≥26 h) were significantly associated with bowel resection in incarcerated groin hernia patients by using the chi-square test. Factors such as leukocyte count, NLR, presentation of bowel obstruction, and duration of incarceration were analyzed using multivariate logistic regression analysis. We found that NLR, presentation of bowel obstruction, and duration of incarceration were independently and significantly related to bowel resection in incarcerated groin hernia patients. CONCLUSIONS An elevated NLR can serve as a biomarker for the prediction of severity of incarcerated groin hernias. Additionally, incarcerated groin hernia patients who present with bowel obstruction or with duration of intestinal incarceration longer than 26 h have an increased risk for bowel resection.

Anti-angiogenic and anti-inflammatory effect of Magnolol in the oxygen-induced retinopathy model.

OBJECTIVE: In the present study, we investigated the effects of Magnolol on the retinal neovascularization (RNV) and local glial cells in an oxygen-induced retinopathy (OIR) model and explored their molecular mechanisms. MATERIALS AND METHODS: Neonatal C57BL/6J mice were subjected to 75% O2 ± 5% from postnatal day (P) 7 to P12 and subsequently returned to room air. Mice were injected with 25 mg/kg Magnolol intraperitoneally once a day from P12 to P17, then retinas were harvested and flat-mounted to assess the retinal vessels, astrocytes and microglia. To clarify the molecular mechanisms of Magnolol, we observed the level of inflammatory cytokines such as interleukin (IL)-1ß, IL-6, monocyte chemoattractant protein-1, tumor necrosis factor-α, and analyzed the hypoxia-inducible factor (HIF)-1α/vascular endothelial growth factor (VEGF) pathway in OIR mice. RESULTS: Intraperitoneal administration of Magnolol resulted in significant reduction of RNV without retinal toxicity or perturbation of developmental retinal angiogenesis. In addition, Magnolol preserved the astrocyte morphology and diminished the activation of microglia. Moreover, Magnolol down regulated the expression of inflammatory cytokines and inactivated the HIF-1α/VEGF pathway. CONCLUSIONS: These results indicated that Magnolol might have potential for the treatment of pathological retinal angiogenesis and glial dysfunctions via anti-inflammation and inhibition of HIF-1α/VEGF pathway.

Myc-interacting zinc-finger protein 1 positively regulates Wnt signalling by protecting Dishevelled from Dapper1-mediated degradation.

Wnt signalling regulates embryonic development and tissue homoeostasis by modulating cell proliferation, differentiation and migration. Dapper1 (Dpr1) has been shown to be an important key negative regulator of Wnt signalling by promoting Dishevelled (Dvl) degradation. In the present study, we found that Myc-interacting zinc-finger protein 1 (MIZ1) interacts with Dpr1 and this interaction attenuates the ability of Dpr1 to induce Dvl2 degradation, thus enhancing Wnt signalling. Mechanistically, MIZ1 is translocated from the nucleus to the cytoplasm upon Wnt3a stimulation or overexpression of Dpr1 and Dvl2, disrupting the interaction between Dpr1 and Dvl2. Furthermore, MIZ1 can promote the proliferation of breast cancer MDA-MB-231 and BT-549 cells through Wnt signalling and reverse the anti-proliferative effect of Dpr1 on colorectal cancer Caco-2. Together, our findings establish a novel layer of Wnt signalling regulation via the MIZ1-Dpr1-Dvl axis.

Base-pair resolution DNA methylation sequencing reveals profoundly divergent epigenetic landscapes in acute myeloid leukemia.

We have developed an enhanced form of reduced representation bisulfite sequencing with extended genomic coverage, which resulted in greater capture of DNA methylation information of regions lying outside of traditional CpG islands. Applying this method to primary human bone marrow specimens from patients with Acute Myelogeneous Leukemia (AML), we demonstrated that genetically distinct AML subtypes display diametrically opposed DNA methylation patterns. As compared to normal controls, we observed widespread hypermethylation in IDH mutant AMLs, preferentially targeting promoter regions and CpG islands neighboring the transcription start sites of genes. In contrast, AMLs harboring translocations affecting the MLL gene displayed extensive loss of methylation of an almost mutually exclusive set of CpGs, which instead affected introns and distal intergenic CpG islands and shores. When analyzed in conjunction with gene expression profiles, it became apparent that these specific patterns of DNA methylation result in differing roles in gene expression regulation. However, despite this subtype-specific DNA methylation patterning, a much smaller set of CpG sites are consistently affected in both AML subtypes. Most CpG sites in this common core of aberrantly methylated CpGs were hypermethylated in both AML subtypes. Therefore, aberrant DNA methylation patterns in AML do not occur in a stereotypical manner but rather are highly specific and associated with specific driving genetic lesions.

Identification and characterization of Hoxa9 binding sites in hematopoietic cells.

The clustered homeobox proteins play crucial roles in development, hematopoiesis, and leukemia, yet the targets they regulate and their mechanisms of action are poorly understood. Here, we identified the binding sites for Hoxa9 and the Hox cofactor Meis1 on a genome-wide level and profiled their associated epigenetic modifications and transcriptional targets. Hoxa9 and the Hox cofactor Meis1 cobind at hundreds of highly evolutionarily conserved sites, most of which are distant from transcription start sites. These sites show high levels of histone H3K4 monomethylation and CBP/P300 binding characteristic of enhancers. Furthermore, a subset of these sites shows enhancer activity in transient transfection assays. Many Hoxa9 and Meis1 binding sites are also bound by PU.1 and other lineage-restricted transcription factors previously implicated in establishment of myeloid enhancers. Conditional Hoxa9 activation is associated with CBP/P300 recruitment, histone acetylation, and transcriptional activation of a network of proto-oncogenes, including Erg, Flt3, Lmo2, Myb, and Sox4. Collectively, this work suggests that Hoxa9 regulates transcription by interacting with enhancers of genes important for hematopoiesis and leukemia.

High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients.

To identify genetic events underlying the genesis and progression of multiple myeloma (MM), we conducted a high-resolution analysis of recurrent copy number alterations (CNAs) and expression profiles in a collection of MM cell lines and outcome-annotated clinical specimens. Attesting to the molecular heterogeneity of MM, unsupervised classification using nonnegative matrix factorization (NMF) designed for array comparative genomic hybridization (aCGH) analysis uncovered distinct genomic subtypes. Additionally, we defined 87 discrete minimal common regions (MCRs) within recurrent and highly focal CNAs. Further integration with expression data generated a refined list of MM gene candidates residing within these MCRs, thereby providing a genomic framework for dissection of disease pathogenesis, improved clinical management, and initiation of targeted drug discovery for specific MM patients.

Acquired retinoschisis resolved after 23Gage pars plana vitrectomy in posterior microphthalmos.

BACKGROUND: Posterior microphthalmos combined with acquired retinoschisis is a rare entity. This report presents a case of acquired retinoschisis in a patient with posterior microphthalmos and discusses the management for such disease. The patient exhibited acquired peripheral retinal schisis in both eyes. CASE PRESENTATION: The patient presented with a fix scotoma and decrease in visual acuity for 2 weeks in his left eye. Ocular examination revealed that his best-corrected visual acuity was 0.6 in right eye and 0.2 in left eye. The patient had amblyopia because of hyperopia with spherical equivalent of +11.75 diopters in the right eye and +12.00 diopters in the left eye. The axial lengths were 18.41 mm in right and 18.43 mm in left eyes respectively. Slip lamp examination found normal anterior segments. Funduscopy showed bilateral retinoschisis in inferotemporal retina. The schisis in right eye was limited to peripheral retina whereas the schisis in left eye was bullous type. The schisis in the left eye extended from the periphery to the posterior macular region in left eye. A pars plana vitrectomy was performed in the left eye and visual acuity was restored to 0.6. CONCLUSION: Posterior microphthalmos combined with retinoschisis is rare. When it appears in peripheral retina, the schisis remains stable. In cases where the schisis extends to posterior pole and affects the macula, surgery in the form of pars plana vitrectomy could be an option.

Temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection.

Exposure to influenza viruses is necessary, but not sufficient, for healthy human hosts to develop symptomatic illness. The host response is an important determinant of disease progression. In order to delineate host molecular responses that differentiate symptomatic and asymptomatic Influenza A infection, we inoculated 17 healthy adults with live influenza (H3N2/Wisconsin) and examined changes in host peripheral blood gene expression at 16 timepoints over 132 hours. Here we present distinct transcriptional dynamics of host responses unique to asymptomatic and symptomatic infections. We show that symptomatic hosts invoke, simultaneously, multiple pattern recognition receptors-mediated antiviral and inflammatory responses that may relate to virus-induced oxidative stress. In contrast, asymptomatic subjects tightly regulate these responses and exhibit elevated expression of genes that function in antioxidant responses and cell-mediated responses. We reveal an ab initio molecular signature that strongly correlates to symptomatic clinical disease and biomarkers whose expression patterns best discriminate early from late phases of infection. Our results establish a temporal pattern of host molecular responses that differentiates symptomatic from asymptomatic infections and reveals an asymptomatic host-unique non-passive response signature, suggesting novel putative molecular targets for both prognostic assessment and ameliorative therapeutic intervention in seasonal and pandemic influenza.

Genomic insights and prognostic significance of novel biomarkers in pancreatic ductal adenocarcinoma: A comprehensive analysis.

Pancreatic ductal adenocarcinoma (PDAC) is a highly prevalent digestive system malignancy, with a significant impact on public health, especially in the elderly population. The advent of the Human Genome Project has opened new avenues for precision medicine, allowing researchers to explore genetic markers and molecular targets for cancer diagnosis and treatment. Despite significant advances in genomic research, early diagnosis of pancreatic cancer remains elusive due to the lack of highly sensitive and specific markers. Therefore, there is a need for in-depth research to identify more precise and reliable diagnostic markers for pancreatic cancer. In this study, we utilized a combination of public databases from different sources to meticulously screen genes associated with prognosis in pancreatic cancer. We used gene differential analysis, univariate cox regression analysis, least absolute selection and shrinkage operator (LASSO) regression, and multivariate cox regression analysis to identify genes associated with prognosis. Subsequently, we constructed a scoring system, validated its validity using survival analysis and ROC analysis, and further confirmed its reliability by nomogram and decision curve analysis (DCA). We evaluated the diagnostic value of this scoring system for pancreatic cancer prognosis and validated the function of the genes using single cell data analysis. Our analysis identifies six genes, including GABRA3, IL20RB, CDK1, GPR87, TTYH3, and KCNA2, that were strongly associated with PDAC prognosis. Clinical prognostic models based on these genes showed strong predictive power not only in the training set but also in external datasets. Functional enrichment analysis revealed significant differences between high- and low-risk groups mainly in immune-related functions. Additionally, we explored the potential of the risk score as a marker for immunotherapy response and identified key factors within the tumor microenvironment. The single-cell RNA sequencing analysis further enriched our understanding of cell clusters and six hub genes expressions. This comprehensive investigation provides valuable insights into pancreatic PDAC and its intricate immune landscape. The identified genes and their functional significance underscore the importance of continued research into improving diagnosis and treatment strategies for PDAC.

Identification and validation of a gap junction protein related signature for predicting the prognosis of renal clear cell carcinoma.

Background: Gap junction proteins (GJPs) are a class of channel proteins that are closely related to cell communication and tumor development. The objective of this study was to screen out GJPs related prognostic signatures (GRPS) associated with clear cell renal cell carcinoma (ccRCC). Materials and Methods: GJPs microarray data for ccRCC patients were obtained from The Gene Expression Omnibus (GEO) database, along with RNA sequencing data for tumor and paired normal tissues from The Cancer Genome Atlas (TCGA) database. In the TCGA database, least absolute shrinkage and selection Operator (LASSO) and Cox regression models were used to identify GJPs with independent prognostic effects as GRPS in ccRCC patients. According to the GRPS expression and regression coefficient from the multivariate Cox regression model, the risk score (RS) of each ccRCC patient was calculated, to construct the RS prognostic model to predict survival. Overall survival (OS) and progression-free survival (PFS) analyses; gene pan-cancer analysis; single gene survival analysis; gene joint effect analysis; functional enrichment analysis; tumor microenvironment (TME) analysis; tumor mutational burden (TMB) analysis; and drug sensitivity analysis were used to explore the biological function, mechanism of action and clinical significance of GRPS in ccRCC. Further verification of the genetic signature was performed with data from the GEO database. Finally, the cytofunctional experiments were used to verify the biological significance of GRPS associated GJPs in ccRCC cell lines. Results: GJA5 and GJB1, which are GRPS markers of ccRCC patients, were identified through LASSO and Cox regression models. Low expression of GJA5 and GJB1 is associated with poor patient prognosis. Patients with high-RS had significantly shorter OS and PFS than patients with low-RS (p< 0.001). The risk of death for individuals with high-RS was 1.695 times greater than that for those with low-RS (HR = 1.695, 95%CI= 1.439-1.996, p< 0.001). Receiver Operating Characteristic (ROC) curve showed the great predictive power of the RS prognostic model for the survival rate of patients. The area under curve (AUC) values for predicting 1-year, 3-year and 5-year survival rates were 0.740, 0.781 and 0.771, respectively. The clinical column chart was also reliable for predicting the survival rate of patients, with AUC values of 0.859, 0.846 and 0.796 for predicting 1-year, 3-year and 5-year survival, respectively. The GRPS was associated with immune cell infiltration, the TME, the TMB, and sensitivity to chemotherapy drugs. Further in vitro experiments showed that knockdown of GJA5 or GJB1 could promote the proliferation, migration and epithelial-mesenchymal transition (EMT) and inhibit apoptosis of ccRCC cells. Conclusion: GJA5 and GJB1 could be potential biological markers for predicting survival in patients with ccRCC.