Clinical and Prognostic Implications of an Immune-Related Risk Model Based on TP53 Status in Lung Adenocarcinoma

Song, Xinzhang; Chen, Qiang; Wang, Jifan; Mao, Qixing; Xia, Wenjie; Xu, Lin; Jiang, Feng; Dong, Gaochao

doi:10.21203/rs.3.rs-105337/v1

Cited by 2 publications

(2 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The genes included in the molecular typing of LUAD often include EGFR, ALK, ROS1, BRAF, NTRK1/2/3, MET, and RET, and the mutation rate of functional driver genes is about 60%, among which KRAS, EGFR mutations and EML4-ALK fusion is the most common driver gene, accounting for about 35% to 40% (23)(24)(25). The study by Jones et al showed that KRAS G12C mutation was associated with worse disease-free survival after complete resection of stage I-III LUAD (26).…”

Section: Discussionmentioning

confidence: 99%

P2RY14 downregulation in lung adenocarcinoma: a potential therapeutic target associated with immune infiltration

Xu¹,

Xu²,

Yao³

et al. 2022

J Thorac Dis

View full text Add to dashboard Cite

Background: The current study aimed to investigate the interrelation between P2RY14 and the prognosis of patients suffering from lung adenocarcinoma (LUAD) following surgery. Methods:The differentially expressed gene (DEG) P2RY14 was screened by the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Immunology Database and Analysis Portal (ImmPort) databases. The relationship between P2RY14 and clinical data of LUAD was analyzed in TCGA and Kaplan-Meier (KM)-plotter databases. The association of P2RY14 with immune cells and immune-related expressed genes was analyzed in the Tumor Immune Estimation Resource (TIMER) database. A retrospective analysis of the 100 patients clinical data undergoing pulmonary adenocarcinoma surgery admitted to Nanjing Chest Hospital.Immunohistochemistry (IHC) analysis was carried out to evaluate the P2RY14 expression in lung cancer tissues, and quantitative reverse transcription PCR (RT-qPCR) was used to confirm the mRNA expression of this gene in LUAD tissues. And their survival was evaluated. KM method and the log-rank test were used for univariate survival analysis, and the Cox regression method was employed for multivariate survival analysis.Results: P2Y14 was the DEG identified by the database. P2Y14 expression was upregulated in para-cancer tissues in comparison to cancer tissues. Patients suffering from LUAD who have high P2RY14 expression had a better prognosis than those with low expression. P2RY14 expression was shown to be substantially linked with immune invasion in the TIMER database. Finally, the trial included 100 patients, of which 80 died and 20 survived with a mean overall survival (OS) of 48 months. Between the high and low expression groups of P2RY14, there were statistically significant variations in the clinical stage and differentiation degree (P<0.05).Cox regression analysis revealed that differentiation degree, smoking history, and P2RY14 expression were independent risk factors for the prognosis of LUAD patients (all P<0.05).Conclusions: P2RY14 can substantially prolong the OS of patients suffering from LUAD and can be utilized as a new LUAD predictive biomarker. P2RY14 may be related to LUAD immune invasion and have an essential role in inhibiting tumor cell immune escape within the LUAD microenvironment.

show abstract

Section: Discussionmentioning

confidence: 99%

P2RY14 downregulation in lung adenocarcinoma: a potential therapeutic target associated with immune infiltration

Xu¹,

Xu²,

Yao³

et al. 2022

J Thorac Dis

View full text Add to dashboard Cite

show abstract

“…In particular, abnormal p53 contributes to immune escape, resulting in an immunosuppressive microenvironment (55). It has been shown that TP53 mutation could lead to reduced immunity in LUAD patients (56). As a result, higher frequencies of TP53 mutation in patients in the CSFI-high group might have contributed to the immunosuppressed state of these patients.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a combined ferroptosis and immune prognostic signature for lung adenocarcinoma

Li¹,

Ge²,

Fei³

et al. 2022

Transl Cancer Res TCR

View full text Add to dashboard Cite

Background: Studies have shown that the regulation of ferroptosis could be a new approach to cancer treatment and abnormal ferroptosis is closely associated with a dysregulated immune response. However, a combined signature with ferroptosis-related genes (FRGs) and immune-related genes (IRGs) is necessary to be constructed for predicting prognoses and guiding individualized precision therapy of lung adenocarcinoma (LUAD) patients.Methods: In this study, based on the Cancer Genome Atlas (TCGA) cohort, prognosis-related FRGs and IRGs were first identified and incorporated into the Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression model to generate a combined signature of ferroptosis-and immune-related genes (CSFI) values to predict the overall survivals (OSs) of LUAD patients. And patients with LUAD from the Gene Expression Omnibus (GEO) database were applied for the validation set. Nomogram was constructed based on multivariate Cox regression analysis. Subsequently, ferroptosis, immunity, and gene mutation status of patients between the CSFI-high and -low groups were compared. Additionally, the enrichment pathways in CSFI-high and -low groups were explored by Gene Ontology (GO), Kyoto Gene and Genome Encyclopedia (KEGG) and Gene Set Enrichment Analysis (GSEA) analyses.Results: As a result, the CSFI-low group showed a good prognosis instead of the CSFI-high group. CSFI was identified to be an independent prognosis factor for LUAD. In general, there were ferroptosis-and immune-suppressive states in CSFI-high patients. Notably, the mutation frequencies of TP53 were higher in CSFI-high patients.Conclusions: In LUAD, CSFI which served as a novel classifier was offered for predicting the prognoses of patients and contributing to guiding personalized targeted therapy of patients. Therefore, based on these findings, it was believed that a synergistic treatment of ferroptosis and immunity would be more effective on LUAD patients with low CSFI values.

show abstract

Clinical and Prognostic Implications of an Immune-Related Risk Model Based on TP53 Status in Lung Adenocarcinoma

Cited by 2 publications

References 51 publications

P2RY14 downregulation in lung adenocarcinoma: a potential therapeutic target associated with immune infiltration

P2RY14 downregulation in lung adenocarcinoma: a potential therapeutic target associated with immune infiltration

Development and validation of a combined ferroptosis and immune prognostic signature for lung adenocarcinoma

Contact Info

Product

Resources

About