Identifying a lactic acid metabolism-related gene signature contributes to predicting prognosis, immunotherapy efficacy, and tumor microenvironment of lung adenocarcinoma

Zhao, Fangchao; Wang, Zengying; Li, Zhirong; Liu, Shiquan; Li, Shujun

doi:10.3389/fimmu.2022.980508

Cited by 14 publications

(13 citation statements)

References 30 publications

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“…We also constructed a nomogram to improve the predictive value of the formula for evaluating the prognosis of patients with HCC. In summary, our study clari ed the signi cance of exosome-related genes in the development of NAFLD-related HCC.Recently, there are many models constructed with diseases-related genes for the diagnosis and prognosis of various diseases including HCC [13,14]. It has been revealed that the diagnostic e ciency of multigene model is usually higher than that of single-gene model [15].…”

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confidence: 68%

“…Liang et al constructed a formula with 10 ferroptosis-related genes to predict overall survival (OS) time of HCC patients [13]. Zhao et al identi ed a formula with 5 lactic acid metabolism-related genes to predict prognosis and immunotherapy e cacy of lung adenocarcinoma [14]. Chen et al developed a ve-gene prognostic model to predict the risk and prognosis of colon cancer [16].…”

mentioning

confidence: 99%

“…Recently, there are many models constructed with diseases-related genes for the diagnosis and prognosis of various diseases including HCC [13,14]. It has been revealed that the diagnostic e ciency of multigene model is usually higher than that of single-gene model [15].…”

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confidence: 99%

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Predictive effect and clinical significance of exosome-related genes for Nonalcoholic fatty liver disease-related hepatocellular carcinoma

Ding

Zhang

et al. 2023

Preprint

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Nonalcoholic fatty liver disease (NAFLD) is a multifactorial metabolic syndrome which could develop into hepatocellular carcinoma (HCC). Exosomes could mediate intercellular communications and play key roles in the occurrence and development of many diseases including NAFLD and HCC. However, expressions and roles of the genes related to exosomes in NAFLD-related HCC remain unclear. The objective of this study was to investigate the expressions and diagnostic values of exosome-related genes in NAFLD-related HCC. Firstly, we identified 15 genes related to exosome secretion by database searching. Two subgroups of patients with NAFLD-related HCC from GEO database were identified on the basis of exosome-related genes. High level of memory CD4 + T cells and low expressions of Immune Checkpoint genes were observed in the group with highly expressed genes which could promote exosome secretion. Subsequently, the logistic regression analysis was used to generate the formula based on three selected exosome-related genes in NAFLD-related HCC cohort. Receiver operating characteristic (ROC) curve analysis confirmed the good predictive power of formula. Functional analysis showed abundant metabolism-related pathways were screened out in DEGs between the high and low risk-score groups. The risk score from the formula was also positively correlated with memory CD4 + T cells and negatively associated with Immune Checkpoint genes. Finally, prognostic potential of the Exosome-related formula was analyzed in HCC cohort from TCGA database, and patients in the group with highly expressed exosome-promoted genes showed significantly reduced overall survival. We also constructed a nomogram to improve the predictive value of the formula for evaluating the prognosis of patients with HCC. In summary, our study clarified the significance of exosome-related genes in the development of NAFLD-related HCC.

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confidence: 68%

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confidence: 99%

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Predictive effect and clinical significance of exosome-related genes for Nonalcoholic fatty liver disease-related hepatocellular carcinoma

Ding

Zhang

et al. 2023

Preprint

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“…The nomogram is frequently used to determine the prognosis of cancer [ 39 ]. Some nomograms regarding the precise prediction of LUAD patients’ prognoses have been demonstrated in previous studies [ 40 , 41 ]. After combining the risk signature with other clinical characteristics, precise nomograms for OS, PFS, and DFS that are clinically applicable were developed in this study.…”

Section: Discussionmentioning

confidence: 99%

An ICD-Associated DAMP Gene signature predicts survival and immunotherapy response of patients with lung adenocarcinoma

Liang

et al. 2023

Respir Res

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Background While some lung adenocarcinoma (LUAD) patients benefit long-term from treatment with immune checkpoint inhibitors, the sad reality is that a considerable proportion of patients do not. The classification of the LUAD tumor microenvironment (TME) can be used to conceptually comprehend primary resistance mechanisms. In addition, the most recent research demonstrates that the release of damage-associated molecular pattern (DAMP) in TME by immunogenic cell death (ICD) may contribute to the adaptive immune response. Currently, however, there is no such comprehensive research on this topic in LUAD patients. Therefore, we set out to investigate how to reverse the poor infiltration characteristics of immune cells and boost antitumor immunity by identifying DAMP model. Methods In this study, ICD-related DAMP genes were selected to investigate their effects on the prognosis of LUAD. To create a risk signature using the TCGA-LUAD cohort, the univariate COX regression and the least absolute shrinkage and selection operator regression were carried out, and the results were verified in a GEO dataset. Subsequently, the multivariate COX regression was applied to establish a prognostic nomogram. And the ESTIMATE and ssGSEA algorithms were utilized to analyze immune activity and the TIDE algorithm was for responsiveness to immunotherapy. Moreover, clinical tissue samples were used to verify the differential expression of 9 DAMP genes in the signature. Results We identified two distinct DAMP molecular subtypes, and there are remarkable differences in survival probability between the two subtypes, and patients with higher levels of DAMP-related genes are “hot tumors” with increased immune activity. In addition, 9 DAMP genes were selected as prognostic signature genes, and clinical outcomes and immunotherapy response were better for participants in the low-risk group. Importantly, according to the area under the curve (AUC) value in evaluating the efficacy of immunotherapy, this signature is superior to existing predictors, such as PD-L1 and TIDE. Conclusions Our study suggests ICD plays an important part in modeling the TME of LUAD patients. And this signature could be utilized as a reliable predictor to estimate clinical outcomes and predict immunotherapy efficacy among LUAD patients.

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“…Kaplan-Meier (KM) survival analysis was used to test the survival difference between the two subgroups. In addition, we utilized ROC curves to compare the effectiveness of our model with previous studies ( 16 – 19 ).…”

Section: Methodsmentioning

confidence: 99%

Construction and validation of a T cell proliferation regulator-related signature for predicting prognosis and immunotherapy response in lung adenocarcinoma

Chang

Cheng

et al. 2023

Front. Immunol.

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BackgroundAs the main executor of immunotherapy, T cells significantly affect the efficacy of immunotherapy. However, the contribution of the T cell proliferation regulator to the prognosis of lung adenocarcinoma (LUAD) and immunotherapy is still unclear.MethodsBased on T cell proliferation regulators, LUAD samples from The Cancer Genome Atlas (TCGA) were divided into two different clusters by consensus clustering. Subsequently, the T cell proliferation regulator (TPR) signature was constructed according to the prognostic T cell proliferation regulators. Combined with clinical information, a nomogram for clinical practice was constructed. The predictive ability of the signature was verified by the additional Gene Expression Omnibus (GEO) dataset. We also analyzed the differences of tumor microenvironment (TME) in different subgroups and predicted the response to immunotherapy according to the TIDE algorithm. Finally, we further explored the role of ADA (Adenosine deaminase) in the lung adenocarcinoma cell lines through the knockdown of ADA. ResultsAccording to the consensus clustering, there were differences in survival and tumor microenvironment between two different molecular subtypes. T cell proliferation regulator-related signature could accurately predict the prognosis of LUAD. The low-risk group had a higher level of immune infiltration and more abundant immune-related pathways, and its response to immunotherapy was significantly better than the high-risk group (Chi-square test, p<0.0001). The knockdown of ADA inhibited proliferation, migration, and invasion in lung adenocarcinoma cell lines.ConclusionT cell proliferation regulators were closely related to the prognosis and tumor microenvironment of LUAD patients. And the signature could well predict the prognosis of LUAD patients and their response to immunotherapy. ADA may become a new target for the treatment of LUAD.

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Identifying a lactic acid metabolism-related gene signature contributes to predicting prognosis, immunotherapy efficacy, and tumor microenvironment of lung adenocarcinoma

Cited by 14 publications

References 30 publications

Predictive effect and clinical significance of exosome-related genes for Nonalcoholic fatty liver disease-related hepatocellular carcinoma

Predictive effect and clinical significance of exosome-related genes for Nonalcoholic fatty liver disease-related hepatocellular carcinoma

An ICD-Associated DAMP Gene signature predicts survival and immunotherapy response of patients with lung adenocarcinoma

Construction and validation of a T cell proliferation regulator-related signature for predicting prognosis and immunotherapy response in lung adenocarcinoma

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