scholarly journals Systemic analyses of expression patterns and clinical features for GIMAPs family members in lung adenocarcinoma

Aging ◽  
2020 ◽  
Vol 12 (20) ◽  
pp. 20413-20431
Author(s):  
Sisi Deng ◽  
Zhi Zhang ◽  
Xiaoli Lu ◽  
Qi Zhou ◽  
Shilin Xia ◽  
...  
2022 ◽  
Vol 14 (1) ◽  
Author(s):  
Thinh T. Nguyen ◽  
Hyun-Sung Lee ◽  
Bryan M. Burt ◽  
Jia Wu ◽  
Jianjun Zhang ◽  
...  

Abstract Background Lung adenocarcinoma, the most common type of lung cancer, has a high level of morphologic heterogeneity and is composed of tumor cells of multiple histological subtypes. It has been reported that immune cell infiltration significantly impacts clinical outcomes of patients with lung adenocarcinoma. However, it is unclear whether histologic subtyping can reflect the tumor immune microenvironment, and whether histologic subtyping can be applied for therapeutic stratification of the current standard of care. Methods We inferred immune cell infiltration levels using a histological subtype-specific gene expression dataset. From differential gene expression analysis between different histological subtypes, we developed two gene signatures to computationally determine the relative abundance of lepidic and solid components (denoted as the L-score and S-score, respectively) in lung adenocarcinoma samples. These signatures enabled us to investigate the relationship between histological composition and clinical outcomes in lung adenocarcinoma using previously published datasets. Results We found dramatic immunological differences among histological subtypes. Differential gene expression analysis showed that the lepidic and solid subtypes could be differentiated based on their gene expression patterns while the other subtypes shared similar gene expression patterns. Our results indicated that higher L-scores were associated with prolonged survival, and higher S-scores were associated with shortened survival. L-scores and S-scores were also correlated with global genomic features such as tumor mutation burdens and driver genomic events. Interestingly, we observed significantly decreased L-scores and increased S-scores in lung adenocarcinoma samples with EGFR gene amplification but not in samples with EGFR gene mutations. In lung cancer cell lines, we observed significant correlations between L-scores and cell sensitivity to a number of targeted drugs including EGFR inhibitors. Moreover, lung cancer patients with higher L-scores were more likely to benefit from immune checkpoint blockade therapy. Conclusions Our findings provided further insights into evaluating histology composition in lung adenocarcinoma. The established signatures reflected that lepidic and solid subtypes in lung adenocarcinoma would be associated with prognosis, genomic features, and responses to targeted therapy and immunotherapy. The signatures therefore suggested potential clinical translation in predicting patient survival and treatment responses. In addition, our framework can be applied to other types of cancer with heterogeneous histological subtypes.


2021 ◽  
Vol 12 ◽  
Author(s):  
Guomin Wu ◽  
Qihao Wang ◽  
Ting Zhu ◽  
Linhai Fu ◽  
Zhupeng Li ◽  
...  

This study aimed to establish a prognostic risk model for lung adenocarcinoma (LUAD). We firstly divided 535 LUAD samples in TCGA-LUAD into high-, medium-, and low-immune infiltration groups by consensus clustering analysis according to immunological competence assessment by single-sample gene set enrichment analysis (ssGSEA). Profile of long non-coding RNAs (lncRNAs) in normal samples and LUAD samples in TCGA was used for a differential expression analysis in the high- and low-immune infiltration groups. A total of 1,570 immune-related differential lncRNAs in LUAD were obtained by intersecting the above results. Afterward, univariate COX regression analysis and multivariate stepwise COX regression analysis were conducted to screen prognosis-related lncRNAs, and an eight-immune-related-lncRNA prognostic signature was finally acquired (AL365181.2, AC012213.4, DRAIC, MRGPRG-AS1, AP002478.1, AC092168.2, FAM30A, and LINC02412). Kaplan–Meier analysis and ROC analysis indicated that the eight-lncRNA-based model was accurate to predict the prognosis of LUAD patients. Simultaneously, univariate COX regression analysis and multivariate COX regression analysis were undertaken on clinical features and risk scores. It was illustrated that the risk score was a prognostic factor independent from clinical features. Moreover, immune data of LUAD in the TIMER database were analyzed. The eight-immune-related-lncRNA prognostic signature was related to the infiltration of B cells, CD4+ T cells, and dendritic cells. GSEA enrichment analysis revealed significant differences in high- and low-risk groups in pathways like pentose phosphate pathway, ubiquitin mediated proteolysis, and P53 signaling pathway. This study helps to treat LUAD patients and explore molecules related to LUAD immune infiltration to deeply understand the specific mechanism.


2019 ◽  
Author(s):  
Wenbo Liu ◽  
Jun Ni ◽  
Faheem Shah ◽  
Kaiqin Ye ◽  
Hao Hu ◽  
...  

APYRASEs, which directly regulated the intra- and extra-cellular ATP homeostasis, plays a pivotal role in the regulation of the adaptations to various stresses in mammals, bacteria and plants. In the present study, we identified and characterized the wheat APYRASE family members at the genomic level. The results showed that a total of eight APY homologs with conserved ACR domains were identified. The wheat APYs were further analyzed bioinformatically of their sequence alignment, phylogenetic relations and conserved motifs. Although they share highly conserved secondary structure and tertiary structure, the wheat APYs could be mainly categorized into three groups, according to the phylogenetic and structural analysis. Further, these APYs exhibited similar expression patterns in the root and shoot, among which TaAPY3-1 and TaAPY3-3 had the highest expression level. The time-course expression patterns of the eight APYs in the wheat seedlings in response to the biotic stress and abiotic stress were also investigated. TaAPY3-2, TaAPY3-3, and TaAPY6 exhibited strong sensitivity to all kinds of stresses in the leaves. Some APYs showed specific expression responses, such as TaAPY6 to the heavy metal stress, and TaAPY7 to the heat and salt stress. These results suggested that the stress-inducible APYs could have potential roles in the regulation of the adaptation to the environmental stresses. Moreover, the catalytic activity of TaAPY3-1 was further analyzed in the in vitro system. The results showed that TaAPY3-1 protein exhibited high catalytic activity in degradation of ATP and ADP, but not GTP, CTP and TTP. It also has an extensive range of temperature adaptability, but rather preferred relative acid pH conditions. In this study, the genome-wide identification and characterization of the APYs in wheat could be useful for further genetic modifications to generate high-stress tolerant wheat cultivars.


Plants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1356
Author(s):  
Zhaohan Zhang ◽  
Shahid Ali ◽  
Tianxu Zhang ◽  
Wanpeng Wang ◽  
Linan Xie

Abscisic acid (ABA) plays a crucial role in various aspects of plant growth and development, including fruit development and ripening, seed dormancy, and involvement in response to various environmental stresses. In almost all higher plants, ABA signal transduction requires three core components; namely, PYR/PYL/RCAR ABA receptors (PYLs), type 2C protein phosphatases (PP2Cs), and class III SNF-1-related protein kinase 2 (SnRK2s). The exploration of these three core components is not comprehensive in soybean. This study identified the GmPYL-PP2C-SnRK2s gene family members by using the JGI Phytozome and NCBI database. The gene family composition, conservation, gene structure, evolutionary relationship, cis-acting elements of promoter regions, and its coding protein domains were analyzed. In the entire genome of the soybean, there are 21 PYLs, 36 PP2Cs, and 21 SnRK2s genes; further, by phylogenetic and conservation analysis, 21 PYLs genes are classified into 3 groups, 36 PP2Cs genes are classified into seven groups, and 21 SnRK2s genes are classified into 3 groups. The conserved motifs and domain analysis showed that all the GmPYLs gene family members contain START-like domains, the GmPP2Cs gene family contains PP2Cc domains, and the GmSnRK2s gene family contains S_TK domains, respectively. Furthermore, based on the high-throughput transcriptome sequencing data, the results showed differences in the expression patterns of GmPYL-PP2C-SnRK2s gene families in different tissue parts of the same variety, and the same tissue part of different varieties. Our study provides a basis for further elucidation of the identification of GmPYL-PP2C-SnRK2s gene family members and analysis of their evolution and expression patterns, which helps to understand the molecular mechanism of soybean response to abiotic stress. In addition, this provides a conceptual basis for future studies of the soybean ABA core signal pathway.


2019 ◽  
Vol 8 (10) ◽  
pp. e1629260
Author(s):  
Yufeng Lv ◽  
Zhong Huang ◽  
Yan Lin ◽  
Yuan Fang ◽  
Zhichao Chen ◽  
...  

2012 ◽  
Vol 195 (1) ◽  
pp. 47-57 ◽  
Author(s):  
Fabiana Csukasi ◽  
Livia Donaire ◽  
Ana Casañal ◽  
Llúcia Martínez-Priego ◽  
Miguel A. Botella ◽  
...  

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