Identification of Key Genes Related to CD8+ T-Cell Infiltration as Prognostic Biomarkers for Lung Adenocarcinoma

Du, Minjun; Liang, Yicheng; Liu, Zixu; Li, Xingkai; Liang, Mei; Zhou, Boxuan; Gao, Yushun

doi:10.3389/fonc.2021.693353

Cited by 10 publications

(7 citation statements)

References 59 publications

(70 reference statements)

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“…These results were con rmed again in our study, and we also found that in addition to B cells and T cells, MFNG was also closely related to many other immune cells, indicating that MFNG might lead to tumorigenesis by regulating the immune microenvironment in the body. Du et al found that ALG3 was associated with CD8 + T cell in ltration and closely related to the prognosis of LUAD [32] , while we found that ALG3 had a higher correlation with Tcm and mast cells. Tcm [33] and Mast cells [34] have been proved to be closely related to tumorigenesis, which suggests that ALG3 may participate in tumor progression by regulating these immune cells, which needs further study.…”

Section: Discussioncontrasting

confidence: 45%

A novel glycosylation-related gene signature predicts survival in patients with lung adenocarcinoma

Liang

Chen

et al. 2022

Preprint

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Background: Lung adenocarcinoma (LUAD) is the most common malignant tumor that seriously affects a huge number of human health. It is reported that abnormal levels of glycosylation promote the progression and poor prognosis of lung cancer. Hence, we aimed to explore the prognostic signature related to glycosyltransferases (GTs) for LUAD. Method: Based on the data of gene expression profiles obtained from The Cancer Genome Atlas (TCGA) database and GTs obtained from the GlycomeDB database, we identified differentially expressed GTs-related genes (DGTs) between control and LUAD samples. The latent functions and pathways of DGTs were detected by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and ingenuity pathway analysis (IPA) methods. Univariate and multivariate Cox regression analyses were then performed to screen the candidate prognostic genes to conduct a prognostic risk model for LUAD. Kaplan-Meier(K-M) curve was operated to assess the overall survival (OS) of LUAD patients. The accuracy and specificity of the constructed risk model were evaluated by receiver operating characteristic analysis (ROC). In addition, the infiltrating immune cells in the tumor environment were analyzed using the single-sample gene set enrichment analysis (ssGSEA) algorithm. Results: A total of 48 DGTs were identified, contained 37 upregulated and 11 downregulated DGTs, which were mainly enriched in the processes of glycosylation, glycoprotein biosynthetic process, glycosphingolipid biosynthesis-lacto and neolacto series, and cell-mediated immune response. Furthermore, B3GNT3, MFNG, GYLTL1B, ALG3, and GALNT13 were screeded as prognostic genes to construct a risk model for LUAD that divided patients into a high-and low-risk group. K-M curve analysis suggested that high-risk patients showed shorter OS compared with low-risk patients. ROC analysis demonstrated the risk model presented a better ability for diagnosing LUAD. Additionally, the portion of infiltrating aDC and Tgd were higher in the high-risk group than the low-risk group. Spearman correlation analysis manifested that the prognostic genes (MFNG and ALG3) were significantly correlated with infiltrating immune cells. Conclusion: We established a novel GTs-related risk model for the prognosis of LUAD patients, providing new therapeutic targets for LUAD.

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Section: Discussioncontrasting

confidence: 45%

A novel glycosylation-related gene signature predicts survival in patients with lung adenocarcinoma

Liang

Chen

et al. 2022

Preprint

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“…Tian et al showed that the high infiltration of M0 macrophages and resting CD4 memory T cells are associated with an unfavorable prognosis in glioma. 30 Conversely, previous studies have suggested that the infiltration of the CD8 T cells was positively correlated to improve prognosis and survival in several cancers, including melanoma, 31 lung adenocarcinoma, 32 and cutaneous angiosarcoma. 33 In line with these results, this might partly explain that the high‐ ITGA5 group had a poorer prognosis than that of the low‐ ITGA5 group in patients with LSCC.…”

Section: Discussionmentioning

confidence: 99%

ITGA5 is an independent prognostic biomarker and potential therapeutic target for laryngeal squamous cell carcinoma

Zhou

Wei

Shen

et al. 2022

Clinical Laboratory Analysis

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Background Integrin α5 (ITGA5) was involved in a variety of cancers. However, the role of ITGA5 in laryngeal squamous cell carcinoma (LSCC) remains unknown. Methods The expression of ITGA5 and the corresponding clinicopathological parameters of LSCC patients the TCGA database. Five datasets (GSE51985, GSE59102, GSE84957, GSE27020, and GSE65858) were downloaded from the GEO database as validation sets. Kaplan–Meier plotter, Cox regression analysis, and nomogram were performed to determine the prognostic value of ITGA5 in LSCC. GO, KEGG, and GSEA were used to explore the underlying biological functions of ITGA5 in LSCC. The algorithms ESTIMATE and CIBERSORT were adopted to evaluate the association between ITGA5 and the infiltration of the immune cells. The algorithm pRRophetic was used to estimate the response to chemotherapeutic drugs. Results The expression of ITGA5 was higher in the LSCC samples and linked to poor overall survival and recurrence‐free survival. Further, the Cox regression analysis confirmed that high expression of ITGA5 was an independent unfavorable prognostic factor. The predictive performance of nomogram based on the expression of ITGA5 was accurate and practical. The functional enrichment analysis confirmed that ITGA5 was related to the construction of the components and structures of the extracellular matrix. Finally, patients with high ITGA5 expression were more likely to benefit from docetaxel and gemcitabine. Conclusion The expression of ITGA5 was elevated in the LSCC and was a predictor for prognosis and chemotherapeutic response in LSCC patients.

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“…We rstly revealed that AMDHD1 was highly expressed in LUAD and its overexpression was correlated with patients' poor outcome. GAPDH was found to be one of ve key genes related to prognosis and CD8 + T-cell in ltration in LUAD [22,23]. Moreover, Sakthidhasan et al [24] con rmed the apoptotic and anti-proliferative potential of GAPDH against human lung carcinoma.…”

Section: Discussionmentioning

confidence: 98%

A novel glutamine metabolism-related gene signature for prognostic prediction in patients with lung adenocarcinoma

Jiang¹,

Wen

et al. 2022

Preprint

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Background Lung adenocarcinoma (LUAD) is the major non-small-cell lung cancer pathological subtype with poor prognosis worldwide. Glutamine metabolism (GM) plays an important role in tumor development and progression. Herein, we aimed to construct a GM-associated prognostic gene signature to predict survival in patients with LUAD. Methods The gene expression profiles of patients with LUAD were downloaded from the Cancer Genome Atlas (TCGA), and two independent datasets for validation were downloaded from the Gene Expression Omnibus (GEO). 41 GM-related genes were downloaded from the previous literatures and used to establish GM-related risk model (names as Score). The prognostic GM-associated gene signatures were identified using univariate Cox and LASSO analyses. Kaplan-Meier and receiver operating characteristic (ROC) curves were performed to validate the predictive efficacy of the prognostic signatures. The correlation between the GMScore and tumor-infiltrated immune cells was evaluated using CIBERSORTx analysis. A nomogram was used to predict the survival probability of LUAD based on GMScore. Results We constructed a prognostic signature comprising 7 GM-related genes (AMDHD1, GAPDH, GCLC, GLS2, HAL, SLC38A2, SLC7A5). The Kaplan-Meier curves validated the reliable predictive ability of the prognostic signature in TCGA and two GEO datasets (p < 0.001, p = 0.001, and p = 0.003, respectively). The area under the curve (AUC) of the ROC curves validated the predictive accuracy of the risk model. We constructed a nomogram to predict the survival probability of LUAD, and the calibration curves showed well predictive accuracy. Finally, functional analysis also revealed distinct immune status between high and low GMScore groups in LUAD. Conclusion Our study constructed a GM-related gene signature, and indicated that GMScore could serve as a novel biomarker for predicting patients' survival in LUAD.

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Identification of Key Genes Related to CD8+ T-Cell Infiltration as Prognostic Biomarkers for Lung Adenocarcinoma

Cited by 10 publications

References 59 publications

A novel glycosylation-related gene signature predicts survival in patients with lung adenocarcinoma

A novel glycosylation-related gene signature predicts survival in patients with lung adenocarcinoma

ITGA5 is an independent prognostic biomarker and potential therapeutic target for laryngeal squamous cell carcinoma

A novel glutamine metabolism-related gene signature for prognostic prediction in patients with lung adenocarcinoma

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