Dataset Information

Fatty acid metabolism-related genes as a novel module biomarker for kidney renal clear cell carcinoma: Bioinformatics modeling with experimental verification.

ABSTRACT:

Backgrounds

Lipid metabolism reprogramming is a hallmark of cancer, however, the associations between fatty acid metabolism (FAM) and kidney renal clear cell carcinoma (KIRC) prognosis are still less investigated.

Methods

The gene expression and clinical data of KIRC were obtained from TCGA. Using Cox regression and LASSO regression, a novel prognostic risk score model based on FAM-related genes was constructed, and a nomogram for prediction of overall survival rate of patients with KIRC was proposed. The correlation between risk score and the immune cell infiltration, immune-related function and tumor mutation burden (TMB) were explored. Finally, a hub gene was extracted from the model, and RT-qPCR, Western blot, Immunohistochemical, EdU, Scratch assay and Transwell experiments were conducted to validate and decipher the biomarker role of the hub gene in KIRC theranostics.

Results

In this study, a novel risk score model and a nomogram were constructed based on 20 FAM-related genes to predict the prognosis of KIRC patients with AUC>0.7 at 1-, 3-, and 5-years. Patients in different subgroups showed different phenotypes in immune cell infiltration, immune-related function, TMB, and sensitivity to immunotherapy. In particular, the hub gene in the model, i.e., ACADM, was significantly down-expressed in human KIRC samples, and the knockdown of OCLN promoted proliferation, migration and invasion of KIRC cells in vitro.

Conclusions

In this study, a novel risk score model and a module biomarker based on FAM-related genes were screened for KIRC prognosis. More clinical carcinogenic validations will be performed for future translational applications of the findings.

SUBMITTER: Jia Z

PROVIDER: S-EPMC10502355 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Fatty acid metabolism-related genes as a novel module biomarker for kidney renal clear cell carcinoma: Bioinformatics modeling with experimental verification.

Jia Zongming Z Fu Zhenyu Z Kong Ying Y Wang Chengyu C Zhou Bin B Lin Yuxin Y Huang Yuhua Y

Translational oncology 20230912

<h4>Backgrounds</h4>Lipid metabolism reprogramming is a hallmark of cancer, however, the associations between fatty acid metabolism (FAM) and kidney renal clear cell carcinoma (KIRC) prognosis are still less investigated.<h4>Methods</h4>The gene expression and clinical data of KIRC were obtained from TCGA. Using Cox regression and LASSO regression, a novel prognostic risk score model based on FAM-related genes was constructed, and a nomogram for prediction of overall survival rate of patients wi ...[more]

PMID: 37708719

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Project description:Background and Objectives: Calcium-binding protein 39-like (CAB39L) has been reported to be downregulated and possessed diagnostic and prognostic values in several types of cancer. However, the clinical value and mechanism of CAB39L in kidney renal clear cell carcinoma (KIRC) remain unclear. Materials and Methods: Bioinformatics analysis was conducted using different databases including TCGA, UALCAN, GEPIA, LinkedOmics, STRING, and TIMER. One-way variance analysis and t-test were chosen to investigate the statistical differences of CAB39L expression in KIRC tissues with different clinical characteristics. The receiver operating characteristic (ROC) curve was chosen to assess the discriminatory capacity of CAB39L. Kaplan-Meier curves were employed for assessing the influence of CAB39L on the progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) of KIRC patients. The independent prognostic significance of clinical parameters for OS such as CAB39L expression in KIRC patients was estimated by Cox analysis. A series of in vitro functional experiments and Western blot (WB) and immunohistochemistry (IHC) were used to validate the relative protein expression and function of CAB39L. Results: The mRNA and protein levels of CAB39L were relatively downregulated in KIRC samples. Meanwhile, hypermethylation of the CAB39L promoter region was possibly associated with its low expression in KIRC. The ROC curve showed that the mRNA expression of CAB39L had a strong diagnostic value for both early and late KIRC. Kaplan-Meier survival curves indicated that a higher mRNA level of CAB39L predicted good PFS, DSS, and OS. The mRNA expression of CAB39L was an independent prognostic factor (hazard ratio = 0.6, p = 0.034) identified by multivariate Cox regression analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis exhibited that CAB39L was mainly associated with substance and energy metabolism. Finally, overexpression of CAB39L impaired the proliferation and metastasis of KIRC cells in vitro. Conclusions: CAB39L possesses prognostic and diagnostic capacity in KIRC.

Project description:Paired-like homeodomain transcription factor 1 (PITX1) is involved in numerous biological processes, including cell growth, progression, and invasion in various malignant tumors. Nevertheless, the relationship between PITX1 and kidney renal clear cell carcinoma (KIRC) remains unclear. The clinical role and functions of PITX1 were analyzed by integrating multiple open-access online datasets. Further experimental verification was performed via quantitative real-time PCR (qRT-PCR) to detect the expression of PITX1 in 10 pairs of KIRC tissues. Our results revealed that PITX1 mRNA was overexpressed in tumor tissues compared with normal tissues in the TCGA-KIRC database (p < 0.001) and numerous independent cohorts (p < 0.05). Further, high expression of PITX1 mRNA was detected in KIRC tissues compared with adjacent normal tissues in our center by qRT-PCR (N = 10, p < 0.05). Logistic regression analysis demonstrated that the PITX1 level was positively associated with KIRC patients, T and M stages, histologic grade, and pathologic stage (all p < 0.05). Survival analysis showed that upregulation of PITX1 mRNA was associated with poor overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) (all p < 0.05). Univariate/multivariate Cox hazard regression analysis revealed that PITX1 was an independent risk factor for OS in patients with KIRC (HR = 1.998, p = 0.003). Accordingly, the time-independent receiver operating characteristic (ROC) curve confirmed that PITX1 had good predictive efficacy for OS and DSS. Meanwhile, a prediction model constructed by nomogram was used to predict the OS of KIRC patients, and the calibration plot indicated this model shows high accuracy. We also revealed some downstream target genes of PITX1-related signaling pathways. Our finding suggested that high PITX1 mRNA expression may act as an independent predictive factor of poor prognosis in patients with KIRC. The prognostic model based on the nomogram would be instrumental in evaluating the survival rate in KIRC patients.

Dataset Information

Fatty acid metabolism-related genes as a novel module biomarker for kidney renal clear cell carcinoma: Bioinformatics modeling with experimental verification.

Backgrounds

Methods

Results

Conclusions

Publications

Fatty acid metabolism-related genes as a novel module biomarker for kidney renal clear cell carcinoma: Bioinformatics modeling with experimental verification.

Similar Datasets

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