Identification of an Autophagy-Related Prognostic Signature for Clear Cell Renal Cell Carcinoma

Chen, Mei; Zhang, Shufang; Nie, Zhenyu; Wen, Xiaohong; Gao, Yuanhui

doi:10.3389/fonc.2020.00873

Cited by 25 publications

(22 citation statements)

References 40 publications

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“…Survival analysis and Cox regression analysis indicated that expression of IGFLR1 was a prognostic factor in ccRCC patients, rather than an independent prognostic factor (Sichani et al, 2010). Besides, although a number of previous studies have constructed prognostic risk models based on clinical factors, gene signature, or taking both into account (Chang et al, 2018;Chen et al, 2019Chen et al, , 2020Xu D. et al, 2020;Xu W.H. et al, 2020), IGFLR1 has not been reported as a factor in model construction.…”

Section: Discussionmentioning

confidence: 99%

IGFLR1 as a Novel Prognostic Biomarker in Clear Cell Renal Cell Cancer Correlating With Immune Infiltrates

Song

Shao

et al. 2020

Front. Mol. Biosci.

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ObjectiveInsulin Growth Factor-Like receptor 1 (IGFLR1) reflects progressive disease and confers a poor prognosis in clear cell renal cell cancer (ccRCC). However, extensive studies highlighting the mechanisms involved in how IGFLR1 triggers the progression of ccRCC remain lacking.MethodsIn the present study, the expression level of IGFLR1 mRNA and correlation between IGFLR1 expression and prognosis of ccRCC were analyzed based on The Cancer Genome Atlas (TCGA) ccRCC cohort. Further, we analyzed methylation and copy number variation to try to explain the difference in IGFLR1 expression. Subsequently, we investigated the correlation between IGFLR1 and tumor-infiltrating immune cells with the aid of TIMER (Tumor Immune Estimation Resource). The potential candidates’ genes associated with IGFLR1 were screened by variation analysis, which were used for further enrichment analysis of signaling pathways and immune gene sets to infer the certain function and corresponding mechanisms in which IGFLR1 was involved in ccRCC. Finally, we establish prognostic risk models using multivariate Cox regression analysis and analyzed the possible involvement of IGFLR1 in chemotherapeutic drug resistance.ResultsThe results showed that upregulated IGFLR1 was detected in ccRCC compared with para-cancer tissues and significantly affected the prognosis of ccRCC (overall survival: Logrank p < 0.0001; disease free survival: Logrank p = 0.022). Univariate and multivariate analyses indicated that IGFLR1 was an independent prognostic factor for ccRCC (HR = 2.064, p = 0.006) and the risk prognostic model based on age, M, level of platelet and calcium and IGFLR1 expression had satisfying predictive ability. The correlation analysis showed that the expression level of IGFLR1 was positively correlated with the abundance of myeloid derived suppressor cell and their marker genes in ccRCC significantly. IGFLR1 may be related to the regulatory activation, intercellular adhesion of lymphocytes and drug resistance in cancer.ConclusionThese findings suggested that IGFLR1 was significantly associated with the prognosis in a variety of cancers, particularly ccRCC. IGFLR1 may play an important role in tumor related immune infiltration and showed potential diagnostic, therapeutic and prognostic value in ccRCC.

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Section: Discussionmentioning

confidence: 99%

IGFLR1 as a Novel Prognostic Biomarker in Clear Cell Renal Cell Cancer Correlating With Immune Infiltrates

Song

Shao

et al. 2020

Front. Mol. Biosci.

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“…A study conducted by Ding et al on invasive liver cancer yielded similar ndings [32]. Bioinformatics analysis performed by Chen et al revealed that the biological processes of the clear cell renal cell carcinoma (ccRCC) low-risk group was related to the regulation of autophagy [33]. Li et al also found that the positive regulation of autophagy and enrichment of immune activation pathways were more associated with patients in the low-risk group than those in the high-risk group [14].…”

Section: Discussionmentioning

confidence: 89%

“…Dunkle et al found that the rate of apoptosis of peripheral T cells with CFLAR de ciency increased [42]. Following bioinformatics analysis of ARGs in ccRCC, Chen et al found that PRKCQ was associated with poor OS in patients with ccRCC, and may be used to evaluate their prognosis [33]. In summary, these genes are often associated with immune response and autophagy in tumors.…”

Section: Discussionmentioning

confidence: 99%

A Novel Autophagy-Related lncRNA Gene Signature to Improve the Prognosis of Patients with Melanoma

Ding

Tayier

et al. 2020

Preprint

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Background: Autophagy and long non-coding RNAs (lncRNAs) have been the focus of research on the pathogenesis of melanoma. However, the autophagy network of lncRNAs in melanoma has not been reported. The purpose of this study was to investigate the lncRNA prognostic markers related to melanoma autophagy and predict the prognosis of patients with melanoma.Methods: We downloaded RNA-sequencing data and clinical information of melanoma from The Cancer Genome Atlas. The co-expression of autophagy-related genes (ARGs) and lncRNAs was analyzed. The risk model of autophagy-related lncRNAs was established by univariate and multivariate COX regression analyses, and the best prognostic index was evaluated combined with clinical data. Finally, gene set enrichment analysis was performed on patients in the high- and low-risk groups.Results: According to the results of the univariate COX analysis, only the overexpression of LINC00520 was associated with poor overall survival, unlike HLA-DQB1-AS1, USP30-AS1, AL645929, AL365361, LINC00324, and AC055822. The results of the multivariate COX analysis showed that the overall survival of patients in the high-risk group was shorter than that recorded in the low-risk group (p<0.001). Moreover, in the receiver operating characteristic curve of the risk model we constructed, the area under the curve (AUC) was 0.734, while the AUC of T and N was 0.707 and 0.658, respectively. The Gene Ontology was mainly enriched with the positive regulation of autophagy and the activation of the immune system. The results of the Kyoto Encyclopedia of Genes and Genomes enrichment were mostly related to autophagy, immunity, and melanin metabolism.Conclusion: The positive regulation of autophagy may slow the transition from low-risk patients to high-risk patients in melanoma. Furthermore, compared with clinical information, the autophagy-related lncRNAs risk model may better predict the prognosis of patients with melanoma and provide new treatment ideas.

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“…Previous studies indicated that AGRs-based signature can serve as effective biomarkers for predicting patient's prognosis [22][23][24][25], but the role in sarcoma patients remains unclear. In the present study, two ARGs-based signatures were generated to predict the OS and DFS for sarcoma patients, respectively.…”

Section: Construction Of Arg Signatures For Os and Dfs Of Sarcoma Patmentioning

confidence: 99%

Systematic profiling of diagnostic and prognostic value of autophagy-related genes for sarcoma patients

Wang

Shao

et al. 2021

BMC Cancer

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Background Autophagy-related genes (ARGs) have been confirmed to have an important role in tumorigenesis and tumor microenvironment formation. Nevertheless, a systematic analysis of ARGs and their clinical significance in sarcoma patients is lacking. Methods Gene expression files from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) were used to select differentially expressed genes (DEGs). Differentially expressed ARGs (DEARGs) were determined by matching the DEG and HADb gene sets, which were evaluated by functional enrichment analysis. Unsupervised clustering of the identified DEARGs was conducted, and associations with tumor microenvironment (TME), immune checkpoints, and immune cells were analyzed simultaneously. Two prognostic signatures, one for overall survival (OS) and one for disease-free survival (DFS), were established and validated in an independent set. Results In total, 84 DEARGs and two clusters were identified. TME scores, five immune checkpoints, and several types of immune cells were found to be significantly different between two clusters. Two prognostic signatures incorporating DEARGs showed favorable discrimination and were successfully validated. Two nomograms combining signature and clinical variables were generated. The C-indexes were 0.818 and 0.747 for the OS and DFS nomograms, respectively. Conclusion This comprehensive analyses of the ARG landscape in sarcoma showed novel ARGs related to carcinogenesis and the immune microenvironment. These findings have implications for prognosis and therapeutic responses, which reveal novel potential prognostic biomarkers, promote precision medicine, and provide potential novel targets for immunotherapy.

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Identification of an Autophagy-Related Prognostic Signature for Clear Cell Renal Cell Carcinoma

Cited by 25 publications

References 40 publications

IGFLR1 as a Novel Prognostic Biomarker in Clear Cell Renal Cell Cancer Correlating With Immune Infiltrates

IGFLR1 as a Novel Prognostic Biomarker in Clear Cell Renal Cell Cancer Correlating With Immune Infiltrates

A Novel Autophagy-Related lncRNA Gene Signature to Improve the Prognosis of Patients with Melanoma

Systematic profiling of diagnostic and prognostic value of autophagy-related genes for sarcoma patients

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