scholarly journals Lymphocyte cytosolic protein 2 is a novel prognostic marker in lung adenocarcinoma

2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110596
Author(s):  
Yishan Huo ◽  
Kainan Zhang ◽  
Songtao Han ◽  
Yangchun Feng ◽  
Yongxing Bao

Objective Lymphocyte cytosolic protein 2 (LCP2) is often ectopically expressed in various human tumors. However, the clinical significance and role of LCP2 in lung adenocarcinoma (LUAD) remain unclear. This study explored the prognostic significance of LCP2 in LUAD patients. Methods LCP2 expression in LUAD tissues was analyzed using data from The Cancer Genome Atlas and Genotype-Tissue Expression databases. Western blotting was employed to detect LCP2 expression in LUAD. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to explore signaling pathways mediated by LCP2 co-regulatory genes. Immunohistochemistry was used to examine levels of LCP2 and programmed death ligand 1 (PD-L1) in 68 LUAD patients. Associations between LCP2 expression and clinicopathological features, prognoses, and PD-L1 levels among the LUAD in-patients were analyzed. Results Among the 68 LUAD in-patients, LCP2 expression was correlated with clinical stage and lymph node metastasis. LUAD patients with high LCP2 expression were associated with increased overall survival. LCP2 expression may be associated with an enrichment of several immune functions. Moreover, our immunohistochemistry results demonstrated that LCP2 expression was positively correlated with PD-L1 expression in LUAD tissues. Conclusions In the study, LCP2 was found to be a favorable prognostic biomarker in LUAD patients.

2019 ◽  
Vol 39 (10) ◽  
Author(s):  
Jing Ye ◽  
Haiyan Sun ◽  
Zhengquan Feng ◽  
Qiqin Zhang ◽  
Yongliang Xia ◽  
...  

Abstract Background: Dysregulated expression of long non-coding RNA gastric carcinoma high expressed transcript 1 (lncRNA GHET1) has been observed in several cancers, however, definite conclusion on the prognostic value of lncRNA GHET1 expression in human cancers has not been determined. The aim of this meta-analysis was to evaluate the prognostic significance of lncRNA GHET1 expression in cancers. Methods: PubMed, Web of Science and Embase were comprehensively searched for relevant studies. Meta-analyses of overall survival (OS) and clinicopathological features were conducted. Results: Ten studies were finally analyzed in the present study. High lncRNA GHET1 expression was associated with shorter OS than low lncRNA GHET1 expression in cancers (hazard ratio (HR) = 2.59, 95% CI = 1.93–3.47, P<0.01). Online cross-validation using The Cancer Genome Atlas (TCGA) data observed similar results (HR = 1.10, P<0.05). When compared with low lncRNA GHET1 expression, high lncRNA GHET1 expression was related to larger tumor size (P<0.01), worse differentiation (P<0.01), earlier distant metastasis (P=0.02), earlier lymph node metastasis (P<0.01) and more advanced clinical stage (P<0.01). Conclusion: High lncRNA GHET1 expression is associated with worse cancer prognosis and can serve as a promising prognostic factor of human cancers.


2021 ◽  
Vol 17 ◽  
pp. 117693432110098
Author(s):  
Xuan Luo ◽  
Lei Feng ◽  
WenBo Xu ◽  
XueJing Bai ◽  
MengNa Wu

Lung adenocarcinoma (LUAD) is a tumor with high incidence. This study aimed to identify the central genes of LUAD. LUAD were analyzed by weighted gene co-expression network (WGCNA), and differentially expressed genes (DEGs) were identified. Samples were obtained from The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases and included 515 LUAD samples and 347 normal samples. The WGCNA algorithm generated a total of 10 modules. The top 2 modules (MEturquoise and MEblue) with the highest correlation to LUAD were selected. Ten Hub genes (IL6, CDH1, PECAM1, SPP1, THBS1, HGF, SNCA, CDH5, CAV1, and DLC1) were screened in the intersecting genes of DEGs and WGCNA (MEturquoise and MEblue). Only SPP1 was correlated with LUAD poor survival, indicating that SPP1 may be a key Hub gene for LUAD. The competing endogenous RNA (ceRNA) network was constructed to analyze the regulatory relationship of Hub genes, and SPP1 may be directly regulated by 4 microRNAs (miRNAs) and indirectly regulated by 49 long noncoding RNAs (lncRNAs).


Genes ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 36 ◽  
Author(s):  
Longxiang Xie ◽  
Yifang Dang ◽  
Jinshuai Guo ◽  
Xiaoxiao Sun ◽  
Tiantian Xie ◽  
...  

Keratin 8 (KRT8), a type II basic intermediate filament (IF) protein, is essential for the development and metastasis of various cancers. In this study, by analyzing RNA-seq data from the Cancer Genome Atlas (TCGA)-lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), we have determined the expression profile of KRT8, and assessed its prognostic significance and the possible mechanism underlying the dysregulation. Our results showed that KRT8 mRNA expression was significantly up-regulated in both LUAD and LUSC tissues compared with normal lung tissues. The high KRT8 expression group for LUAD patients significantly reduced overall survival (OS) and recurrence-free survival (RFS). Univariate and multivariate analysis revealed that KRT8 expression was an independent prognostic indicator for poor OS and RFS in LUAD patients. However, KRT8 expression had no prognostic value in terms of OS and RFS for LUSC. By exploring DNA copy number alterations (CNAs) of the KRT8 gene in LUAD, we found that DNA low copy gain (+1 and +2) was associated with elevated KRT8 mRNA expression. From the above findings, we have deduced that KRT8 is aberrantly expressed in LUAD tissues and that its expression might independently predict poor OS and RFS for LUAD patients, but not for LUSC patients.


2021 ◽  
Author(s):  
Jialin Li ◽  
Xinliang Gao ◽  
Suyan Tian ◽  
Mingbo Tang ◽  
Wei Liu

Background: Exosomes are involved in tumorigenesis, growth and metastasis. However, the prognostic value of exosome-related genes in lung adenocarcinoma (LUAD) remains unclear. Methods: Clinical and transcriptome data from The Cancer Genome Atlas LUAD cohort were used to construct a model based on exosome-related genes, which was validated with LUAD data from the Gene Expression Omnibus (GEO). Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were used to explore underlying mechanisms; the single-sample gene set enrichment analysis score was used to determine immune functions. Results: A 19-exosome-related gene signature for overall survival in LUAD was predictive in both The Cancer Genome Atlas and GEO LUAD cohorts. Immune-related and extracellular matrix-related pathways were enriched in differentially expressed genes. Immune states differed between high- and low-risk groups. Conclusion: The novel signature can be used to predict outcomes in LUAD.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Sangsang Chen ◽  
Xuqing Zhu ◽  
Jing Zheng ◽  
Tingting Xu ◽  
Yinmin Xu ◽  
...  

Objective. The abnormal expression of epithelial cell transforming sequence 2 (ECT2) is often considered the driving factor for the growth and invasion of tumors. This study was performed to investigate the regulatory effect of miR-30a-5p and ECT2 on lung adenocarcinoma (LUAD), which provides a basis for the effective clinical treatment of LUAD. Methods. The mature miRNAs, expression data of mRNAs, and clinical data of LUAD were downloaded from The Cancer Genome Atlas (TCGA). The expression levels of ECT2 mRNA and miR-30a-5p in cancer cell lines were detected by qRT-PCR. Western blot was performed to test the expression of ECT2 protein. The targeting relationship between miR-30a-5p and ECT2 was verified by dual-luciferase assay. The CCK-8 method and Transwell assay were conducted to test the viability, migratory, and invasive abilities of cells. Results. ECT2 expression was upregulated in LUAD and was significantly correlated with the LUAD clinical stage and pathologic T stage, and the expression of its upstream regulatory gene miR-30a-5p was downregulated. miR-30a-5p targeted ECT2 in LUAD. Downregulation of ECT2 could inhibit the viability, migration, and invasion of LUAD cells, which could be reversed by simultaneously suppressing the expression of miR-30a-5p. Conclusion. Our results suggested that miR-30a-5p repressed the malignant progression of LUAD via downregulating ECT2. miR-30a-5p and ECT2 may be effective targets for LUAD patients.


2021 ◽  
Vol 12 ◽  
Author(s):  
Min Liang ◽  
Mafeng Chen ◽  
Yinghua Zhong ◽  
Shivank Singh ◽  
Shantanu Singh

Background: Lung adenocarcinoma is one of the most common malignant tumors of the respiratory system, ranking first in morbidity and mortality among all cancers. This study aims to establish a ferroptosis-related gene-based prognostic model to investigate the potential prognosis of lung adenocarcinoma.Methods: We obtained gene expression data with matching clinical data of lung adenocarcinoma from the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The ferroptosis-related genes (FRGs) were downloaded from three subgroups in the ferroptosis database. Using gene expression differential analysis, univariate Cox regression, and LASSO regression analysis, seven FRGs with prognostic significance were identified. The result of multivariate Cox analysis was utilized to calculate regression coefficients and establish a risk-score formula that divided patients with lung adenocarcinoma into high-risk and low-risk groups. The TCGA results were validated using GEO data sets. Then we observed that patients divided in the low-risk group lived longer than the overall survival (OS) of the other. Then we developed a novel nomogram including age, gender, clinical stage, TNM stage, and risk score.Results: The areas under the curves (AUCs) for 3- and 5-years OS predicted by the model were 0.823 and 0.852, respectively. Calibration plots and decision curve analysis also confirmed the excellent predictive performance of the model. Subsequently, gene function enrichment analysis revealed that the identified FRGs are important in DNA replication, cell cycle regulation, cell adhesion, chromosomal mutation, oxidative phosphorylation, P53 signaling pathway, and proteasome processes.Conclusions: Our results verified the prognostic significance of FRGs in patients with lung adenocarcinoma, which may regulate tumor progression in a variety of pathways.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaodong Yang ◽  
Yuexin Zheng ◽  
Zhihai Han ◽  
Xiliang Zhang

Abstract Background As a marker of differentiation, Killer cell lectin like receptor G1 (KLRG1) plays an inhibitory role in human NK cells and T cells. However, its clinical role remains inexplicit. This work intended to investigate the predictive ability of KLRG1 on the efficacy of immune-checkpoint inhibitor in the treatment of lung adenocarcinoma (LUAD), as well as contribute to the possible molecular mechanisms of KLRG1 on LUAD development. Methods Using data from the Gene Expression Omnibus, the Cancer Genome Atlas and the Genotype-Tissue Expression, we compared the expression of KLRG1 and its related genes Bruton tyrosine kinase (BTK), C-C motif chemokine receptor 2 (CCR2), Scm polycomb group protein like 4 (SCML4) in LUAD and normal lung tissues. We also established stable LUAD cell lines with KLRG1 gene knockdown and investigated the effect of KLRG1 knockdown on tumor cell proliferation. We further studied the prognostic value of the four factors in terms of overall survival (OS) in LUAD. Using data from the Gene Expression Omnibus, we further investigated the expression of KLRG1 in the patients with different responses after immunotherapy. Results The expression of KLRG1, BTK, CCR2 and SCML4 was significantly downregulated in LUAD tissues compared to normal controls. Knockdown of KLRG1 promoted the proliferation of A549 and H1299 tumor cells. And low expression of these four factors was associated with unfavorable overall survival in patients with LUAD. Furthermore, low expression of KLRG1 also correlated with poor responses to immunotherapy in LUAD patients. Conclusion Based on these findings, we inferred that KLRG1 had significant correlation with immunotherapy response. Meanwhile, KLRG1, BTK, CCR2 and SCML4 might serve as valuable prognostic biomarkers in LUAD.


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