Prognostic Correlation of an Autophagy-Related Gene Signature in Patients with Head and Neck Squamous Cell Carcinoma

Yang, Cai; Mei, Hongxiang; Peng, Liang; Jiang, Fulin; Xie, Bingjie; Li, Juan

doi:10.1155/2020/7397132

Cited by 25 publications

(22 citation statements)

References 48 publications

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“…The K-M analysis of our model showed a more optimistic trend; the difference in survival curve in the high-and low-risk groups was more significant compared with that of the previous study (He et al, 2021). Moreover, the prognostic risk model of HNSCC patients was more accurate than the models reported in certain previous studies with a preferable AUC for 1 (0.665 vs. 0.634 and 0.663), 3 (0.743 vs. 0.672 and 0.686), and 5 years (0.755 vs. 0.642 and 0.622) (Yang et al, 2020;. Interestingly, the AUC values of our model increased annually, which further strengthened the prognostic effect of the model.…”

Section: Discussioncontrasting

confidence: 55%

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Section: Discussioncontrasting

confidence: 55%

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“…The K-M analysis of our model showed a more optimistic trend; the difference in survival curve in the high- and low-risk groups was more significant compared with that of the previous study ( He et al, 2021 ). Moreover, the prognostic risk model of HNSCC patients was more accurate than the models reported in certain previous studies with a preferable AUC for 1 (0.665 vs. 0.634 and 0.663), 3 (0.743 vs. 0.672 and 0.686), and 5 years (0.755 vs. 0.642 and 0.622) ( Yang et al, 2020 ; Liu B. et al, 2021 ). Interestingly, the AUC values of our model increased annually, which further strengthened the prognostic effect of the model.…”

Section: Discussionmentioning

confidence: 58%

Prognostic Value of a Ferroptosis-Related Gene Signature in Patients With Head and Neck Squamous Cell Carcinoma

Liao

Xiao

et al. 2021

Front. Cell Dev. Biol.

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Background: Ferroptosis is an iron-dependent programmed cell death (PCD) form that plays a crucial role in tumorigenesis and might affect the antitumor effect of radiotherapy and immunotherapy. This study aimed to investigate distinct ferroptosis-related genes, their prognostic value and their relationship with immunotherapy in patients with head and neck squamous cell carcinoma (HNSCC).Methods: The differentially expressed ferroptosis-related genes in HNSCC were filtered based on multiple public databases. To avoid overfitting and improve clinical practicability, univariable, least absolute shrinkage and selection operator (LASSO) and multivariable Cox algorithms were performed to construct a prognostic risk model. Moreover, a nomogram was constructed to forecast individual prognosis. The differences in tumor mutational burden (TMB), immune infiltration and immune checkpoint genes in HNSCC patients with different prognoses were investigated. The correlation between drug sensitivity and the model was firstly analyzed by the Pearson method.Results: Ten genes related to ferroptosis were screened to construct the prognostic risk model. Kaplan-Meier (K-M) analysis showed that the prognosis of HNSCC patients in the high-risk group was significantly lower than that in the low-risk group (P < 0.001), and the area under the curve (AUC) of the 1-, 3- and 5-year receiver operating characteristic (ROC) curve increased year by year (0.665, 0.743, and 0.755). The internal and external validation further verified the accuracy of the model. Then, a nomogram was build based on the reliable model. The C-index of the nomogram was superior to a previous study (0.752 vs. 0.640), and the AUC (0.729 vs. 0.597 at 1 year, 0.828 vs. 0.706 at 3 years and 0.853 vs. 0.645 at 5 years), calibration plot and decision curve analysis (DCA) also shown the satisfactory predictive capacity. Furthermore, the TMB was revealed to be positively correlated with the risk score in HNSCC patients (R = 0.14; P < 0.01). The differences in immune infiltration and immune checkpoint genes were significant (P < 0.05). Pearson analysis showed that the relationship between the model and the sensitivity to antitumor drugs was significant (P < 0.05).Conclusion: Our findings identified potential novel therapeutic targets, providing further potential improvement in the individualized treatment of patients with HNSCC.

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“…Integrin alpha 3 (ITGA3) belongs to the family of integrins, which are heterodimeric integral membrane proteins that function as cell surface adhesion molecules. This gene has been reported in several autophagy-related prognostic models for various tumors, indicating its important role in the progression of tumors 27 – 32 . Mechanistically, it has been reported that miRNA-524-5p inhibits the progression of papillary thyroid carcinoma cells by targeting FOXE1 and ITGA3 in cell autophagy and cycling pathways 33 .…”

Section: Discussionmentioning

confidence: 93%

Identification of an autophagy-related gene signature for predicting prognosis and immune activity in pancreatic adenocarcinoma

Deng¹,

Zhang²,

Lv³

et al. 2022

Sci Rep

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Adenocarcinoma of the pancreas (PAAD) is a cancerous growth that deteriorates rapidly and has a poor prognosis. Researchers are investigating autophagy in PAAD to identify a new biomarker and treatment target. An autophagy-related gene (ARG) model for overall survival (OS) was constructed using multivariate Cox regression analyses. A cohort of the Cancer Genome Atlas (TCGA)-PAAD was used as the training group as a basis for model construction. This prediction model was validated with several external datasets. To evaluate model performance, the analysis with receiver operating characteristic curves (ROC) was performed. The Human Protein Atlas (HPA) and Cancer Cell Line Encyclopedia (CCLE) were investigated to validate the effects of ARGs expression on cancer cells. Comparing the levels of immune infiltration between high-risk and low-risk groups was finished through the use of CIBERSORT. The differentially expressed genes (DEGs) between the low-/high-risk groups were analyzed further via Gene Ontology biological process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, which were used to identify potential small-molecule compounds in Connectivity Map (CMap), followed by half-maximal inhibitory concentration (IC50) examination with PANC-1 cells. The risk score was finally calculated as follows: BAK1 × 0.34 + ITGA3 × 0.38 + BAG3 × 0.35 + APOL1 × 0.26–RAB24 × 0.67519. ITGA3 and RAB24 both emerged as independent prognostic factors in multivariate Cox regression. Each PAAD cohort had a significantly shorter OS in the high-risk group than in the low-risk group. The high-risk group exhibited infiltration of several immune cell types, including naive B cells (p = 0.003), plasma cells (p = 0.044), and CD8 T cells (nearly significant, p = 0.080). Higher infiltration levels of NK cells (p = 0.025), resting macrophages (p = 0.020), and mast cells (p = 0.007) were found in the high-risk group than the low-risk group. The in vitro and in vivo expression of signature ARGs was consistent in the CCLE and HPA databases. The top 3 enriched Gene Ontology biological processes (GO-BPs) were signal release, regulation of transsynaptic signaling, and modulation of chemical synaptic transmission, and the top 3 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were MAPK, cAMP, and cell adhesion molecules. Four potential small-molecule compounds (piperacetazine, vinburnine, withaferin A and hecogenin) that target ARGs were also identified. Taking the results together, our research shows that the ARG signature may serve as a useful prognostic indicator and reveal potential therapeutic targets in patients with PAAD.

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Prognostic Correlation of an Autophagy-Related Gene Signature in Patients with Head and Neck Squamous Cell Carcinoma

Cited by 25 publications

References 48 publications

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Prognostic Value of a Ferroptosis-Related Gene Signature in Patients With Head and Neck Squamous Cell Carcinoma

Identification of an autophagy-related gene signature for predicting prognosis and immune activity in pancreatic adenocarcinoma

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