Shen Shuai II recipe improves renal hypoxia to attenuate renal injury in 5/6 renal ablation/infarction rats and effect evaluation using blood oxygenation level-dependent functional magnetic resonance imaging.

Background: Renal hypoxia plays a key role in the progression of chronic kidney disease (CKD). Shen Shuai II Recipe (SSR) has shown good results in the treatment of CKD as a common herbal formula. This study aimed to explore the effect of SSR on renal hypoxia and injury in CKD rats. Methods: Twenty-five Wistar rats underwent 5/6 renal ablation/infarction (A/I) surgery were randomly divided into three groups: 5/6 (A/I), 5/6 (A/I) + losartan (LOS), and 5/6 (A/I) + SSR groups. Another eight normal rats were used as the Sham group. After 8-week corresponding interventions, blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) was performed to evaluate renal oxygenation in all rats, and biochemical indicators were used to measure kidney and liver function, hemoglobin, and proteinuria. The expression of fibrosis and hypoxia-related proteins was analyzed using immunoblotting examination. Results: Renal oxygenation, evaluated by BOLD-fMRI as cortical and medullary T2* values (COT2* and MET2*), was decreased in 5/6 (A/I) rats, but increased after SSR treatment. SSR also downregulated the expression of hypoxia-inducible factor-1α (HIF-1α) in 5/6 (A/I) kidneys. With the improvement of renal hypoxia, renal function and fibrosis were improved in 5/6 (A/I) rats, accompanied by reduced proteinuria. Furthermore, the COT2* and MET2* were significantly positively correlated with the levels of creatinine clearance rate (Ccr) and hemoglobin, but negatively associated with the levels of serum creatinine (SCr), blood urea nitrogen (BUN), serum cystatin C (CysC), serum uric acid (UA), 24-h urinary protein (24-h Upr), and urinary albumin:creatinine ratio (UACR). Conclusion: The degree of renal oxygenation reduction is correlated with the severity of renal injury in CKD. SSR can improve renal hypoxia to attenuate renal injury in 5/6 (A/I) rats of CKD.

Linking renal hypoxia and oxidative stress in chronic kidney disease: Based on clinical subjects and animal models.

This study aims to explore the relationships between renal function, hypoxia, and oxidative stress in chronic kidney disease (CKD). Seventy-six non-dialysis patients with CKD stages 1-5 and eight healthy subjects were included in the clinical research. They were divided into three groups: healthy subjects, CKD stages 1-3, and CKD stages 4-5. In the animal study, 16 rat models of CKD were established through 5/6 renal ablation/infarction (A/I) surgery, and 8 normal rats were split into 3 groups: Sham, CKD, and losartan groups. Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) was used to measure cortical and medullary T2* values (COT2* and MET2*) in all subjects and rats to evaluate renal oxygenation. Biochemical indicators were used to assess renal function and antioxidant capacity. Furthermore, the effects of losartan on renal fibrosis, hypoxia, and oxidative stress were examined using immunoblotting, colorimetric, and fluorometric assays. The results demonstrated significant positive associations between COT2* and MET2* with estimated glomerular filtration rate (eGFR). Patients with CKD stages 4-5 showed significantly lower serum superoxide dismutase (SOD) levels, which also had positive correlations with eGFR, COT2*, and MET2*. Furthermore, losartan treatment resulted in improved renal function and fibrosis, leading to increased levels of COT2*, MET2*, and SOD levels in 5/6 A/I rats. This was accompanied by reduced levels of hypoxia-inducible factor-1 alpha (HIF-1α) and malondialdehyde. Furthermore, losartan restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), and suppressed the expression of Kelch-like ECH-associated protein 1 (Keap1) in 5/6 A/I kidneys. The study indicates that decline in renal oxygenation and antioxidant capacity is associated with the severity of renal failure in CKD. Losartan can potentially alleviate renal hypoxia and oxidative stress in the treatment of CKD via Keap1-Nrf2/HO-1 pathway.

Shen-Shuai-II-Recipe inhibits tubular inflammation by PPARα-mediated fatty acid oxidation to attenuate fibroblast activation in fibrotic kidneys.

BACKGROUND: Shen Shuai Ⅱ Recipe (SSR) is clinically used to treat chronic kidney diseases (CKDs) with remarkable efficacy and safety. In earlier research, we found the anti-inflammatory, antioxidant, and mitochondrial protective properties of SSR in hypoxic kidney injury model, which is closely related to its renal protection. Further work is needed to understand the underlying molecular mechanisms. PURPOSE: Further investigation of the mechanisms of action of SSR against renal interstitial fibrosis (RIF) building on previous research leads. METHODS: Rats receiving CKD model surgery were given with Fenofibrate or SSR once a day for eight weeks. In vitro, the NRK-52E cells were treated with SSR in the presence or absence of 10 µM Sc75741, 0.5 µM PMA, or 1 µM fenofibrate under 1% O2. The effects of SSR on NF-κB/NLRP3 inflammatory cascade, secretion of pro-inflammatory cytokines, fatty acid oxidation (FAO), and renal tubular injury were determined by immunoblotting, luminex liquid suspension chip assay, transmission electron microscopy, and Oil red O staining. Next, we delivered PPARα-interfering sequences to kidney tissue and NRK-52E cells by adeno-associated virus (AAV) injection and siRNA transfection methods. Finally, we evaluated the effect of renal tubular cells on fibroblast activation by co-culture method. RESULTS: SSR attenuated the release of IL-18, VEGF, and MCP1 cytokines, inhibited the activation of NF-κB/NLRP3 cascade, increased the PPARα, CPT-1α, CPT-2, ACADL, and MCAD protein expression, and improved the lipid accumulation. Further studies have demonstrated that one of the ways in which SSR suppresses the inflammatory response to protect renal tubular cells is through the restoration of PPARα-mediated FAO. In addition, by means of co-culture ways, the results demonstrated that SSR attenuated secretion of inflammatory mediators in NRK-52E cells by PPARα/NF-κB/NLRP3 pathway, thereby inhibiting renal fibroblast activation. CONCLUSION: SSR inhibits RIF by suppressing inflammatory response of hypoxia-exposed RTECs through PPARα-mediated FAO.

Identification of genes and pathways associated with menopausal status in breast cancer patients using two algorithms.

BACKGROUND: Menopausal status has a known relationship with the levels of estrogen, progesterone, and other sex hormones, potentially influencing the activity of ER, PR, and many other signaling pathways involved in the initiation and progression of breast cancer. However, the differences between premenopausal and postmenopausal breast cancer patients at the molecular level are unclear. METHODS: We retrieved eight datasets from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) associated with menopausal status in breast cancer patients were identified using the MAMA and LIMMA methods. Based on these validated DEGs, we performed Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Protein-protein interaction (PPI) networks were constructed. We used DrugBank data to investigate which of these validated DEGs are targetable. Survival analysis was performed to explore the influence of these genes on breast cancer patient prognosis. RESULTS: We identified 762 DEGs associated with menopausal status in breast cancer patients. PPI network analysis indicated that these genes are primarily involved in pathways such as the cell cycle, oocyte meiosis and progesterone-mediated oocyte maturation pathways. Notably, several genes played roles in multiple signaling pathways and were associated with patient survival. These genes were also observed to be targetable according to the DrugBank database. CONCLUSION: We identified DEGs associated with menopausal status in breast cancer patients. The association of these genes with several key pathways may promote understanding of the complex characterizations of breast cancer. Our findings offer valuable insights for developing new therapeutic strategies tailored to the menopausal status of breast cancer patients.

Icariside II prevents kidney fibrosis development in chronic kidney disease by promoting fatty acid oxidation.

Renal interstitial fibrosis (RIF) is the main pathological basis for the progression of chronic kidney disease (CKD), however, effective interventions are limited. Here, we investigated the effect of Icariside II (ICA-II) on RIF and explored the underlying mechanisms. Rats receiving 5/6 ablation and infarction (A/I) surgery were gavaged with ICA-II (5 or 10 mg/kg) for 8 weeks. In vitro, TGF-ß1-stimulated NRK-52E cells were treated with ICA-II and (or) oleic acid, etomoxir, ranolazine, fenofibrate, and GW6471. The effects of ICA-II on RIF, fatty acid oxidation, lipid deposition, and mitochondrial function were determined by immunoblotting, Oil red O staining, colorimetric, and fluorometric assays. Using adeno-associated virus injection and co-culture methods, we further determined mechanisms of ICA-II anti-RIF. ICA-II ameliorated the fibrotic responses in vivo and in vitro. RNA-seq analysis indicated that ICA-II regulated fatty acid degradation and PPAR pathway in 5/6 (A/I) kidneys. ICA-II attenuated lipid accumulation and up-regulated expression of PPARα, CPT-1α, Acaa2, and Acadsb proteins in vivo and in vitro. Compared to ICA-II treatment, ICA-II combined with Etomoxir exacerbated mitochondrial dysfunction and fibrotic responses in TGF-ß-treated NRK-52E cells. Importantly, we determined that ICA-II improved lipid metabolism, fatty acid oxidation, mitochondrial function, and RIF by restoring PPARα. Co-culture revealed that ICA-II decreased the expression of Fibronectin, Collagen-I, α-SMA, and PCNA proteins in NRK-49F cells by restoring PPARα of renal tubular cells. ICA-II may serve as a promising therapeutic agent for RIF in 5/6 (A/I) rats, which may be important for the prevention and treatment of CKD.

[Icariin improves renal interstitial fibrosis in a rat model of chronic renal failure by regulating mitochondrial dynamics].

This study aims to explore the effect of icariin(ICA) on mitochondrial dynamics in a rat model of chronic renal failure(CRF) and to investigate the molecular mechanism of ICA against renal interstitial fibrosis(RIF). CRF was induced in male Sprague-Dawley(SD) rats with 5/6(ablation and infarction, A/I) surgery(right kidney ablation and 2/3 infarction of the left kidney). Four weeks after surgery, the model rats were randomized into the following groups: 5/6(A/I) group, 5/6(A/I)+low-dose ICA group, and 5/6(A/I)+high-dose ICA group. Another 12 rats that received sham operation were randomly classified into 2 groups: sham group and sham+ICAH group. Eight weeks after treatment, the expression of collagen-Ⅰ(Col-Ⅰ), collagen-Ⅲ(Col-Ⅲ), mitochondrial dynamics-related proteins(p-Drp1 S616, p-Drp1 S637, Mfn1, Mfn2), and mitochondrial function-related proteins(TFAM, ATP6) in the remnant kidney tissues was detected by Western blot. The expression of α-smooth muscle actin(α-SMA) was examined by immunohistochemical(IHC) staining. The NRK-52 E cells, a rat proximal renal tubular epithelial cell line, were cultured in vitro and treated with ICA of different concentration. Cell viability was detected by CCK-8 assay. In NRK-52 E cells stimulated with 20 ng·mL~(-1) TGF-ß1 for 24 h, the effect of ICA on fibronectin(Fn), connective tissue growth factor(CTGF), p-Drp1 S616, p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 was detected by Western blot, and the ATP content and the mitochondrial morphology were determined. The 20 ng·mL~(-1) TGF-ß1-stimulated NRK-52 E cells were treated with or without 5 µmol·L~(-1) ICA+10 µmol·L~(-1) mitochondrial fusion promoter M1(MFP-M1) for 24 h and the expression of fibrosis markers Fn and CTGF was detected by Western blot. Western blot result showed that the levels of Col-Ⅰ, Col-Ⅲ, and p-Drp1 S616 were increased and the levels of p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 were decreased in 5/6(A/I) group compared with those in the sham group. The levels of Col-Ⅰ, Col-Ⅲ, and p-Drp1 S616 were significantly lower and the levels of p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 were significantly higher in ICA groups than that in 5/6(A/I) group. IHC staining demonstrated that for the expression of α-SMA in the renal interstitium was higher in the 5/6(A/I) group than in the sham group and that the expression in the ICA groups was significantly lower than that in the 5/6(A/I) group. Furthermore, the improvement in the fibrosis, mitochondrial dynamics, and mitochondrial function were particularly prominent in rats receiving the high dose of ICA. The in vitro experiment revealed that ICA dose-dependently inhibited the increase of Fn, CTGF, and p-Drp1 S616, increased p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6, elevated ATP content, and improved mitochondrial morphology of NRK-52 E cells stimulated by TGF-ß1. ICA combined with MFP-M1 further down-regulated the expression of Fn and CTGF in NRK-52 E cells stimulated by TGF-ß1 compared with ICA alone. In conclusion, ICA attenuated RIF of CRF by improving mitochondrial dynamics.

Identification of genes and pathways associated with sex in Non-smoking lung cancer population.

INTRODUCTION: Women represent a higher proportion than men among those with lung cancer in nonsmokers compared to smokers. The reason for this abnormally higher proportion is not yet clear, but sex differences suggest there may be a genetic component at play. MATERIALS AND METHODS: The gene expression determined by Illumina RNA Sequencing and the relevant clinical information of lung cancer patients was download from TCGA. The differentially expressed genes (DEGs) were screened between males and females in both nonsmoking and smoking populations. The top 50 validated DEGs are represented with heatmaps. Based on the DEGs, GO functional and KEGG pathway enrichment analyses were performed. PPI networks were constructed to further illustrate the direct and indirect associations among the DEGs. Survival analysis was performed to explore whether these genes can affect lung cancer patient prognosis. RESULTS: In non-smoking patients, there were significantly more females than males (female 73.0% vs male 27.0%, P < 0.001). Such difference was not found in smoking patients (female 50.7% vs male 49.3%, P = 0.770). A total of 898 DEGs were identified in the non-smoking population, while a total of 992 DEGs were identified in the smoking population. Of these, only 122 genes were shared by both populations. Some pathways were enriched specifical in non-smoking population, such as cAMP signaling pathway and ovarian steroidogenesis. Several proteins related to estrogen function and MAPK/PI3K signaling, such as KRT16, ERBB4 and NTF4, showed differential effects on the lung adenocarcinoma progression in non-smoking males or females. CONCLUSIONS: Some genetic differences between male and female in non-smoking lung adenocarcinoma patients have been identified. Potentially, ER signaling and MAPK/PI3K signaling partially participated in this discrepancy.

Shen Shuai â ¡ Recipe attenuates renal fibrosis in chronic kidney disease by improving hypoxia-induced the imbalance of mitochondrial dynamics via PGC-1α activation.

BACKGROUND: Shen Shuai Ⅱ Recipe (SSR) is an effective Chinese herbal formula for the treatment of patients with chronic kidney disease (CKD) in the clinic and significantly improves 5/6 ablation and infarction (A/I) surgery-induced renal interstitial fibrosis (RIF) and intrarenal hypoxia in rats. However, the underlying molecular mechanisms need further elucidation. PURPOSE: This study aims to investigate the renoprotective mechanisms of SSR in vivo and in vitro. METHODS: CKD model was induced in rats with 5/6 (A/I) surgery. 4 weeks later, rats were treated with vehicle or SSR or Fenofibrate by daily gavage. In vitro, HK2 cells exposed to hypoxia (1% O2) were treated with SSR in the presence or absence of 100 µM MitoTEMPO or 10 µM Mitochondrial Fusion Promoter M1. The effects of SSR on RIF, mitochondrial dynamics, oxidative metabolism, and mitochondrial ROS (mtROS) were determined by immunoblotting, colorimetric, and fluorometric assays according to the experimental protocols. Furthermore, to explore the mechanisms of SSR against RIF, HK2 cells of PGC-1α or MFN2 knockdown under hypoxic stimulation were treated with 400 µg/ml of SSR and (or) 1 µM of ZLN005. RESULTS: The results showed that treatment with SSR significantly improved mitochondrial morphology and function, up-regulated the expression of PGC-1α protein, and inhibited the production of mtROS in 5/6 (A/I) kidneys and hypoxia-treated HK2 cells, which may be closely correlated with its anti-RIF effect. In addition, compared to wild-type HK2 cells, the roles of SSR in improving mitochondrial dynamics and energy metabolism were greatly diminished in HK2 cells of PGC-1α knockdown under hypoxic exposure. More importantly, compared to ZLN005 or SSR combined with ZLN005 treatment, MFN2-deficient HK2 cells exhibited the increased protein levels of FN, α-SMA, TGF-ß1 and cleaved IL-1ß in response to hypoxic stimulation. CONCLUSION: SSR exerted the renoprotective effects by improving mitochondrial dynamics under hypoxic condition via PGC-1α activation.

Identification of genes and pathways related to breast cancer metastasis in an integrated cohort.

BACKGROUND: Breast cancer is the most common malignant disease in women. Metastasis is the most common cause of death from this cancer. Screening genes related to breast cancer metastasis may help elucidate the mechanisms governing metastasis and identify molecular targets for antimetastatic therapy. The development of advanced algorithms enables us to perform cross-study analysis to improve the robustness of the results. MATERIALS AND METHODS: Ten data sets meeting our criteria for differential expression analyses were obtained from the Gene Expression Omnibus (GEO) database. Among these data sets, five based on the same platform were formed into a large cohort using the XPN algorithm. Differentially expressed genes (DEGs) associated with breast cancer metastasis were identified using the differential expression via distance synthesis (DEDS) algorithm. A cross-platform method was employed to verify these DEGs in all ten selected data sets. The top 50 validated DEGs are represented with heat maps. Based on the validated DEGs, Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Protein interaction (PPI) networks were constructed to further illustrate the direct and indirect associations among the DEGs. Survival analysis was performed to explore whether these genes can affect breast cancer patient prognosis. RESULTS: A total of 817 DEGs were identified using the DEDS algorithm. Of these DEGs, 450 genes were validated by the second algorithm. Enriched KEGG pathway terms demonstrated that these 450 DEGs may be involved in the cell cycle and oocyte meiosis in addition to their functions in ECM-receptor interaction and protein digestion and absorption. PPI network analysis for the proteins encoded by the DEGs indicated that these genes may be primarily involved in the cell cycle and extracellular matrix. In particular, several genes played roles in multiple signalling pathways and were related to patient survival. These genes were also observed to be targetable in the CTD2 database. CONCLUSIONS: Our study analysed multiple cross-platform data sets using two different algorithms, helping elucidate the molecular mechanisms and identify several potential therapeutic targets of metastatic breast cancer. In addition, several genes exhibited promise for applications in targeted therapy against metastasis in future research.

A gene-based risk score model for predicting recurrence-free survival in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) remains the most frequent liver cancer, accounting for approximately 90% of primary liver cancers worldwide. The recurrence-free survival (RFS) of HCC patients is a critical factor in devising a personal treatment plan. Thus, it is necessary to accurately forecast the prognosis of HCC patients in clinical practice. METHODS: Using The Cancer Genome Atlas (TCGA) dataset, we identified genes associated with RFS. A robust likelihood-based survival modeling approach was used to select the best genes for the prognostic model. Then, the GSE76427 dataset was used to evaluate the prognostic model's effectiveness. RESULTS: We identified 1331 differentially expressed genes associated with RFS. Seven of these genes were selected to generate the prognostic model. The validation in both the TCGA cohort and GEO cohort demonstrated that the 7-gene prognostic model can predict the RFS of HCC patients. Meanwhile, the results of the multivariate Cox regression analysis showed that the 7-gene risk score model could function as an independent prognostic factor. In addition, according to the time-dependent ROC curve, the 7-gene risk score model performed better in predicting the RFS of the training set and the external validation dataset than the classical TNM staging and BCLC. Furthermore, these seven genes were found to be related to the occurrence and development of liver cancer by exploring three other databases. CONCLUSION: Our study identified a seven-gene signature for HCC RFS prediction that can be used as a novel and convenient prognostic tool. These seven genes might be potential target genes for metabolic therapy and the treatment of HCC.

Construction and validation of a 6-gene nomogram discriminating lung metastasis risk of breast cancer patients.

Breast cancer is the most common malignant disease in women. Metastasis is the foremost cause of death. Breast tumor cells have a proclivity to metastasize to specific organs. The lung is one of the most common sites of breast cancer metastasis. Therefore, we aimed to build a useful and convenient prediction tool based on several genes that may affect lung metastasis-free survival (LMFS). We preliminarily identified 319 genes associated with lung metastasis in the training set GSE5327 (n = 58). Enrichment analysis of GO functions and KEGG pathways was conducted based on these genes. The best genes for modeling were selected using a robust likelihood-based survival modeling approach: GOLGB1, TMEM158, CXCL8, MCM5, HIF1AN, and TSPAN31. A prognostic nomogram for predicting lung metastasis in breast cancer was developed based on these six genes. The effectiveness of the nomogram was evaluated in the training set GSE5327 and the validation set GSE2603. Both the internal validation and the external validation manifested the effectiveness of our 6-gene prognostic nomogram in predicting the lung metastasis risk of breast cancer patients. On the other hand, in the validation set GSE2603, we found that neither the six genes in the nomogram nor the risk predicted by the nomogram were associated with bone metastasis of breast cancer, preliminarily suggesting that these genes and nomogram were specifically associated with lung metastasis of breast cancer. What's more, five genes in the nomogram were significantly differentially expressed between breast cancer and normal breast tissues in the TIMER database. In conclusion, we constructed a new and convenient prediction model based on 6 genes that showed practical value in predicting the lung metastasis risk for clinical breast cancer patients. In addition, some of these genes could be treated as potential metastasis biomarkers for antimetastatic therapy in breast cancer. The evolution of this nomogram will provide a good reference for the prediction of tumor metastasis to other specific organs.

Identification of potential key genes and pathways in hepatitis B virus-associated hepatocellular carcinoma by bioinformatics analyses.

Chronic hepatitis B virus (HBV) is one of the leading causes of hepatocellular carcinoma (HCC). The precise molecular mechanisms by which HBV contributes to HCC development are not fully understood. The key genes and pathways involved in the transformation of nontumor hepatic tissues into HCC tissues in patients with HBV infection are essential to guide the treatment of HBV-associated HCC. Five datasets were collected from the Gene Expression Omnibus database to form a large cohort. Differentially expressed genes (DEGs) were identified between HCC tissues and nontumor hepatic tissues from HBV-infected patients using the 'limma' package. The top 50 upregulated and top 50 downregulated DEGs in HCC vs. nontumor tissues were demonstrated in subsets by heat maps. Based on the DEGs, Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathways enrichment analyses were performed. Several key pathways of the up- and downregulated DEGs were identified and presented by protein-protein interaction (PPI) networks. A total of 1,934 DEGs were identified. The upregulated DEGs were primarily associated with the 'cell cycle'. Among the DEGs enriched in the 'cell cycle' pathway, 6 genes had a log2-fold change >2: SFN, BUB1B, TTK, CCNB1, CDK1 and CDC20. The downregulated DEGs were primarily associated with the metabolic pathways, such as 'carbon metabolism', 'glycine, serine and threonine metabolism', 'tryptophan metabolism', 'retinol metabolism' and 'alanine, aspartate and glutamate metabolism'. The DEGs in the 'cell cycle' and 'metabolic pathways' were presented by the PPI networks respectively. Overall, the present study provides new insights into the specific etiology of HCC and molecular mechanisms for the transformation of nontumor hepatic tissues into HCC tissues in patients with a history of HBV infection and several potential therapeutic targets for targeted therapy in these patients.

A 5-gene prognostic nomogram predicting survival probability of glioblastoma patients.

BACKGROUND: Glioblastoma (GBM) remains the most biologically aggressive subtype of gliomas with an average survival of 10 to 12 months. Considering that the overall survival (OS) of each GBM patient is a key factor in the treatment of individuals, it is meaningful to predict the survival probability for GBM patients newly diagnosed in clinical practice. MATERIAL AND METHODS: Using the TCGA dataset and two independent GEO datasets, we identified genes that are associated with the OS and differentially expressed between GBM tissues and the adjacent normal tissues. A robust likelihood-based survival modeling approach was applied to select the best genes for modeling. After the prognostic nomogram was generated, an independent dataset on different platform was used to evaluate its effectiveness. RESULTS: We identified 168 differentially expressed genes associated with the OS. Five of these genes were selected to generate a gene prognostic nomogram. The external validation demonstrated that 5-gene prognostic nomogram has the capability of predicting the OS of GBM patients. CONCLUSION: We developed a novel and convenient prognostic tool based on five genes that exhibited clinical value in predicting the survival probability for newly diagnosed GBM patients, and all of these five genes could represent potential target genes for the treatment of GBM. The development of this model will provide a good reference for cancer researchers.