Identification of a Hypoxia-Related Gene Model for Predicting the Prognosis and Formulating the Treatment Strategies in Kidney Renal Clear Cell Carcinoma

Ning, Xianghui; Li, Ningyang; Qi, Yuanyuan; Li, Songchao; Jia, Zhiyuan; Yang, Jinjian

doi:10.3389/fonc.2021.806264

Cited by 10 publications

(8 citation statements)

References 39 publications

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“…Moreover, timedependent ROC curve analyses suggested the favorable forecasting performance of the signature. Besides, the specificity and accuracy of our eight-gene based signature was superior to some previously reported prognostic signatures in ccRCC (30,31), in terms of AUC values of the ROC curves (Supplementary Table 1). Taken together, our HOX gene-based signature harbored satisfactory accuracy and generalizability in prognosis prediction.…”

Section: Discussionmentioning

confidence: 61%

Comprehensive analysis of a homeobox family gene signature in clear cell renal cell carcinoma with regard to prognosis and immune significance

Zheng

Ning²,

Xia³

et al. 2022

Front. Oncol.

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The homeobox (HOX) family genes have been linked to multiple types of tumors, while their effect on malignant behaviors of clear cell renal cell carcinoma (ccRCC) and clinical significance remains largely unknown. Here, we comprehensively analyzed the expression profiles and prognostic value of HOX genes in ccRCC using datasets from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. We developed a prognostic signature comprising eight HOX genes (HOXB1, HOXA7, HOXB5, HOXD8, HOXD9, HOXB9, HOXA9, and HOXA11) for overall survival prediction in ccRCC and it allowed patients to be subdivided into high- and low-risk groups. Kaplan-Meier survival analysis in all the internal and external cohorts revealed significant difference in clinical outcome of patients in different risk groups, indicating the satisfactory predictive power of the signature. Additionally, we constructed a prognostic nomogram by integrating signature-derived risk score and clinical factors such as gender, age, T and M status, which might be helpful for clinical decision-making and designing tailored management schedules. Immunological analysis revealed that the regulatory T cells (Tregs) infiltrated differently between the two subgroups in both TCGA and ICGC cohorts. ssGSEA method showed that the enrichment scores for mast cells were significantly lower in high-risk group compared with the low-risk group, which was consistent in both TCGA and ICGC cohorts. As for the related immune function, the enrichment scores of APC co-inhibition, para-inflammation, and type II IFN response were consistently lower in high-risk group in both cohorts. Of the eight HOX genes, the mRNA and protein levels of HOXD8 were downregulated in ccRCC than that in normal tissues, and decreased expression of HOXD8 was associated with increased tumor grade and stage, and lymph node metastasis. Survival analysis revealed that lower expression of HOXD8 predicted worse overall survival in ccRCC. In conclusion, our HOX gene-based signature was a favorable indicator to predict the prognosis of ccRCC cases and associated with immune cell infiltration. HOXD8 might be a tumor suppressor gene in ccRCC and a potential predictor of tumor progression.

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Section: Discussionmentioning

confidence: 61%

Comprehensive analysis of a homeobox family gene signature in clear cell renal cell carcinoma with regard to prognosis and immune significance

Zheng

Ning²,

Xia³

et al. 2022

Front. Oncol.

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“…Compared with the widely used response biomarkers of ICIs, PD-L1 level and tumor mutation burden (TMB) ( 37 , 39 ), the TIDE achieved the same favorable and robust prediction capacity for both anti-CTLA4 and anti-PD1 therapies. Several recent studies have reported its utility in predicting or evaluating the therapeutic efficacy of ICIs ( 12 , 40 ). Therefore, we used TIDE to predict the response of ICIs.…”

Section: Discussionmentioning

confidence: 99%

Clinical significance and immune landscape of cuproptosis-related lncRNAs in kidney renal clear cell carcinoma: a bioinformatical analysis

Li¹,

Wu²,

Song³

et al. 2022

Ann Transl Med

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Background: Kidney renal clear cell carcinoma (KIRC) is considered an immunogenic tumor. Cuproptosis is a newly identified copper-induced regulated cell death that relies on mitochondria respiration. Long noncoding RNAs (lncRNAs) have emerged as significant players in tumorigenesis and metastasis. However, there is a huge knowledge gap on the prognostic role of cuproptosis-related lncRNAs in KIRC. And, the clinical value of them is still unknown. Here, we aimed to develop a cuproptosis-related lncRNA prognostic signature in KIRC. Methods:The messenger RNA (mRNA)/lncRNA expression profiles and the clinical information including age, gender, tumor stage, grade, and overall survival (OS) were acquired from The Cancer Genome Atlas (TCGA) database. The included KIRC samples were further randomly assigned into training (n=258) or testing (n=257) data sets. We performed Pearson correlation analysis to identify the cuproptosisrelated lncRNAs and then constructed the prognostic signature using Cox regression analysis and LASSO algorithm. Subsequently, Kaplan-Meier survival analysis, a nomogram, and receiver operating characteristic (ROC) curve were performed to assess the predictive performance of the signature. Moreover, the immune characteristics and drug sensitivity related to the signature were also explored. Results:The signature comprised 7 cuproptosis-related lncRNAs. The patients with a low-risk score had superior OS compared with those with a high-risk score. The survival rates of the high-and low-risk groups were 44.96% and 83.72% (P<0.001). The area under the curve (AUC) value for 1-, 3-, 5-year survival rate reached 0.814, 0.762 and 0.825, respectively. In addition, a nomogram was also generated; the AUC was 0.785 for risk score, higher than that for age (0.593), gender (0.489), grade (0.679), and stage (0.721). The highrisk group had more enriched immune-and tumor-related genes. Patients with low-risk scores were more sensitive to immunotherapy and the small molecular drugs GSK1904529A, tipifarnib, BX-912, FR-180204, and GSK1070916. Meanwhile, the high-risk group tended to be more sensitive to pyrimethamine, MS-275, and CGP-60474.Conclusions: Collectively, we constructed a cuproptosis-related lncRNA prognostic signature with a higher predictive accuracy compared to multiple clinicopathological parameters, which may provide vital guidance for therapeutic strategies in KIRC. Combination of more prognostic biomarkers may further improve the accuracy.

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“…Currently, the development of bioinformatics and the publication of large sequencing cohort data have provided the basis for the study of RCC pathogenesis and prognosis model construction. Ning et al [ 21 ]. detected hypoxia-related genes in KIRC using TCGA and ICGC datasets.…”

Section: Discussionmentioning

confidence: 99%

A comprehensive analysis of the FOX family for predicting kidney renal clear cell carcinoma prognosis and the oncogenic role of FOXG1

Yang

Chen

et al. 2022

Aging

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Previous studies have confirmed that the forkhead box (FOX) superfamily of transcription factors regulates tumor progression and metastasis in multiple cancer. The purpose of this study was to develop a model based on FOX family genes for predicting kidney renal clear cell carcinom (KIRC) prognosis. We downloaded the transcriptional profiles and clinical data of KIRC patients from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. To build a new prognosis model, we screened prognosis-related FOX family genes using Lasso regression and Multivariate Cox regression analyses. Receiver operating characteristic (ROC) curves were used to evaluate model performance. Additionally, a prognostic nomogram was developed using clinical information and selected genes to improve the accuracy of prognostic prediction. We also investigated whether prognosis-related FOX family genes are related to the immune response in KIRC. Finally, we validated the oncogenic role of FOXG1 in KIRC using an in vitro tumor function assay. Six prognosis-related FOX family genes were screened: FOXO1, FOXM1, FOXK2, FOXG1, FOXA1, and FOXD1. The ROC curves indicated that our model was capable of making accurate predictions for 1-, 3-, and 5year overall survival (OS). The nomogram further improved the accuracy of prognostic predictions. In addition, compared to those in patients with low-risk scores, high-risk scores predicted a decreased level of immune cell infiltration and a lower immune response rate. Moreover, the results of in vitro studies confirmed that FOXG1 supports the proliferation and invasion of KIRC.

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Identification of a Hypoxia-Related Gene Model for Predicting the Prognosis and Formulating the Treatment Strategies in Kidney Renal Clear Cell Carcinoma

Cited by 10 publications

References 39 publications

Comprehensive analysis of a homeobox family gene signature in clear cell renal cell carcinoma with regard to prognosis and immune significance

Comprehensive analysis of a homeobox family gene signature in clear cell renal cell carcinoma with regard to prognosis and immune significance

Clinical significance and immune landscape of cuproptosis-related lncRNAs in kidney renal clear cell carcinoma: a bioinformatical analysis

A comprehensive analysis of the FOX family for predicting kidney renal clear cell carcinoma prognosis and the oncogenic role of FOXG1

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