scholarly journals O13‐4: Comprehensive analysis of aquaporin superfamily in lung adenocarcinoma

Respirology ◽  
2021 ◽  
Vol 26 (S3) ◽  
pp. 36-37
2022 ◽  
Author(s):  
Yansong Huo ◽  
Leina Sun ◽  
Jie Yuan ◽  
Hua Zhang ◽  
Zhenfa Zhang ◽  
...  

Abstract Background: Lung adenocarcinoma (LUAD) usually contain heterogeneous histological subtypes, among which the micropapillary (MIP) subtype was associated with poor prognosis while the lepidic (LEP) subtype possessed the most favorable outcome. A more comprehensive analysis involving discovery and public validation cohorts on the two subtypes could better decipher the key biological and evolutionary mechanisms.Methods: We firstly retrospectively studied the survival status of 286 LUAD patients with different subtypes. MIP and LEP components were micro-dissected for whole-exome sequencing (WES). Shared and private alterations as well as genomic alternation characteristics between the two components were investigated. Four public cohorts containing LEP and MIP samples were further selected for genomic profile comparison, novel therapeutic target investigation and immune infiltration quantification.Results: LEP and MIP subtypes exhibited largest disease free survival (DFS) in our patients. A total of 2035 SNV and 2757 InDels were identified in the sequenced LEP and MIP components. EGFR was found with highest mutation frequency. Distinct biological processes or pathways were involved in the evolutionary of the two components. Besides, analyses on copy number variation (CNV) and intratumor heterogeneity further discovered the possible immunosurveillance escape, the discrepancy between mutation and CNV level ITH and the pervasive DNA Damage Response as well as WNT pathway gene alternations in MIP component. Phylogenetic analysis on 5 pairs of LEP and MIP components further confirmed the presence of ancestral EGFR mutations. Through comprehensive analysis in our samples and public cohorts, PTP4A3, NAPRT and RECQL4 were identified as novel therapeutic and diagnostic targets in MIP subtype. Immunosuppression prevalence in MIP component was finally confirmed by multi-omics data.Conclusion: We identified genetic differences responsible for variated prognosis. The subtype evolution trajectory was additionally unraveled. Novel gene targets and the immunological analyses also provided therapeutic suggestions for MIP subtype.


2019 ◽  
Vol 8 (4) ◽  
pp. 1350-1358 ◽  
Author(s):  
Bo Yang ◽  
Jie Li ◽  
Fang Li ◽  
Hongxia Zhou ◽  
Weiwei Shi ◽  
...  

2017 ◽  
Vol 38 (4) ◽  
pp. 2453-2463 ◽  
Author(s):  
Jing Sui ◽  
Ru-Song Yang ◽  
Si-Yi Xu ◽  
Yan-Qiu Zhang ◽  
Cheng-Yun Li ◽  
...  

2021 ◽  
Author(s):  
Fangfang Li ◽  
Chun Huang ◽  
Llingxiao Qiu ◽  
Ping Li ◽  
Guojun Zhang

Abstract Purpose The immunotherapy of lung adenocarcinoma has received more and more attention. Different immune cells can affect other metabolic genes and lifespan, and cell metabolism directly regulates immune cell functions. Therefore, it is crucial to explore the role of immune-related metabolic genes in lung adenocarcinoma. Methods In this study, we divided immune-related metabolic genes into three categories based on different immune characteristics and researched immune and clinical pathology. LASSO regression analysis was used to screen immune-related metabolic genes, and a clinical prediction model of the screened genes was constructed. Finally, we selected the intersection of immune metabolism genes that are highly expressed in the tumor site and immune metabolism genes that are negatively related to survival, and used qRT-PCR for experimental verification. Results We first screened out immune-related metabolic genes that may affect lung cancer tumor progression, and screened out 9 pivot genes (TK1, TCN1, CAV1, ACMSD, HS3ST2, HS3ST5, AMN, ADRA2C, ACOXL) through LASSO regression analysis and constructed Prognosis model. Finally, through the screening of tumor-related immune metabolism genes, we obtained five pivot genes (HMMR, PFKP, RRM2, TCN1 and TK1). Our qRT-PCR results also show that RRM2 is positively correlated with CDK2, CDK4, CDK6, and CDK8, revealing the close relationship between RRM2 and immune cell tumor infiltration. Conclusion We conducted a comprehensive analysis of the immune infiltration of the tumor microenvironment of lung cancer, and finally determined RRM2 as a promising immune metabolism checkpoint for lung adenocarcinoma based on the high correlation of RRM2 with immune cells and CDK family.


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