The low expression of NUP62CL indicates good prognosis and high level of immune infiltration in lung adenocarcinoma

Abstract Background: dedicator of cytokinesis 2 is an atypical guanine exchange factor, which is particularly expressed in hematopoietic cells and modulates the activation along with the migration of immune cells by activating Ras--related C3 botulinum toxin substrate (Rac). Nevertheless, the role of DOCK2 in lung adenocarcinoma (LUAD) remains unclear.Methods: Herein, we performed bioinformatics analysis of lung adenocarcinoma data abstracted from TCGA (The Cancer Genome Altas) and GEO (Gene Expression Omnibus) data resources, and combined with web tools consisting of LinkedOmics, TIMER, and TISIDB. Finally, combined with clinical lung adenocarcinoma samples, we verified the expression of DOCK2 in tissue and its effect on the prognosis of lung adenocarcinoma.Results: In the TCGA lung adenocarcinoma data set, the expression of DOCK2 was down-regulated in tumor tissues and verified in multiple independent cohorts. In addition, the low expression of DOCK2 indicates a poor overall survival(OS) in both TCGA and other GEO data sets and in our clinical samples. COX regression data illustrated that the low expression of DOCK2 was an independent predictor for OS. Functional network analysis shows that DOCK2 participates in immune response through interleukin production, neuroinflammatory response, acquired immune response, leukocyte migration and activation of lymph node cells, and is related to multiple immune-related pathways. Besides, the expression of DOCK2 was remarkably related with many kinds of tumor infiltrating immune cells.Conclusion: combined with bioinformatics analysis and clinical sample verification, our study shows that DOCK2 can independently estimate the prognosis of lung adenocarcinoma and is related to immune infiltration. As a promising prognostic indicator and potential target of immunotherapy, the potential effect of DOCK2 on lung adenocarcinoma and its molecular mechanism are worthy of further discussion.

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Low expression of NLRP1 is associated with a poor prognosis and immune infiltration in lung adenocarcinoma patients

Aging ◽

10.18632/aging.202620 ◽

2021 ◽

Vol 13 (5) ◽

pp. 7570-7588

Author(s):

Edward Shen ◽

Ying Han ◽

Changjing Cai ◽

Ping Liu ◽

Yihong Chen ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Poor Prognosis ◽

Immune Infiltration ◽

Low Expression

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GCT-10. CAN HIGH LEVEL SERUM hCG-β BE CONSIDERED EQUIVALENT TO A DIAGNOSIS OF CHORIOCARCINOMA IN PRIMARY CENTRAL NERVOUS SYSTEM GERM-CELL TUMOR?

Neuro-Oncology ◽

10.1093/neuonc/noaa222.231 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii329-iii330

Author(s):

Hiroaki Motegi ◽

Shigeru Yamaguchi ◽

Yukitomo Ishi ◽

Michinari Okamoto ◽

Akihiro Iguchi ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Germ Cell ◽

Germ Cell Tumor ◽

Good Prognosis ◽

Cell Tumor ◽

University Hospital ◽

Kaplan Meier ◽

Beta Human Chorionic Gonadotropin ◽

High Level

Abstract BACKGROUND Primary central nervous system(CNS) choriocarcinoma(CC) is very rare and has the poorest prognosis among germ cell tumor (GCT). CC usually has extremely high level (HL) of serum beta-human chorionic gonadotropin (bhCG) over than 1,000 mIU/ml. Some studies assign HL bhCG cases to poor prognosis group even without biopsy. The purpose of this study was to find out if there was a good prognosis subset in the HL bh group. MATERIALS AND METHODS We analyzed 103 cases diagnosed with GCT from 1998 to 2019 in Hokkaido University Hospital and reviewed the literature of CNS CC and bhCG. Survival was assessed using Kaplan-Meier method and log-rank statistics between the group with CC component and that with no CC component but HL bhCG. RESULTS One out of 103 our cases was diagnosed as a mixed GCT with CC component and did not respond to treatment and died 9 months later. Two cases were treated as CC because of HL bhCG (1,226 and 2,739 mIU/ml) despite that the biopsy showed only germinomas and survived(105 and 37 months), that is, no CC component. Combining our cases with 69 cases in the literature, all 7 cases with no CC component but HL bhCG survived but the median survival of the other 65 cases with CC component was 38.2 months (P=0.02). CONCLUSION This study has a limitation of selection bias, however, it suggests that patients with no CC component but HL bhCG may have a better prognosis.

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Functions and clinical significance of KLRG1 in the development of lung adenocarcinoma and immunotherapy

BMC Cancer ◽

10.1186/s12885-021-08510-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xiaodong Yang ◽

Yuexin Zheng ◽

Zhihai Han ◽

Xiliang Zhang

Keyword(s):

Gene Expression ◽

Overall Survival ◽

Lung Adenocarcinoma ◽

Molecular Mechanisms ◽

Killer Cell ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Normal Lung ◽

Using Data ◽

Low Expression

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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Identification of key genes associated with lung adenocarcinoma by bioinformatics analysis

Science Progress ◽

10.1177/0036850421997276 ◽

2021 ◽

Vol 104 (1) ◽

pp. 003685042199727

Author(s):

Xinyu Wang ◽

Jiaojiao Yang ◽

Xueren Gao

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Lung Adenocarcinoma ◽

Cox Regression ◽

Enrichment Analysis ◽

Tumor Stage ◽

Gene Expression Omnibus ◽

Poor Overall Survival ◽

Key Genes ◽

Low Expression

Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer, comprising around 40% of all lung cancer. Until now, the pathogenesis of LUAD has not been fully elucidated. In the current study, we comprehensively analyzed the dysregulated genes in lung adenocarcinoma by mining public datasets. Two sets of gene expression datasets were obtained from the Gene Expression Omnibus (GEO) database. The dysregulated genes were identified by using the GEO2R online tool, and analyzed by R packages, Cytoscape software, STRING, and GPEIA online tools. A total of 275 common dysregulated genes were identified in two independent datasets, including 54 common up-regulated and 221 common down-regulated genes in LUAD. Gene Ontology (GO) enrichment analysis showed that these dysregulated genes were significantly enriched in 258 biological processes (BPs), 27 cellular components (CCs), and 21 molecular functions (MFs). Furthermore, protein-protein interaction (PPI) network analysis showed that PECAM1, ENG, KLF4, CDH5, and VWF were key genes. Survival analysis indicated that the low expression of ENG was associated with poor overall survival (OS) of LUAD patients. The low expression of PECAM1 was associated with poor OS and recurrence-free survival of LUAD patients. The cox regression model developed based on age, tumor stage, ENG, PECAM1 could effectively predict 5-year survival of LUAD patients. This study revealed some key genes, BPs, CCs, and MFs involved in LUAD, which would provide new insights into understanding the pathogenesis of LUAD. In addition, ENG and PECAM1 might serve as promising prognostic markers in LUAD.

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Exploration of Tumor Mutation Burden Combined with Immune Infiltrates in the Prognosis of Lung Adenocarcinoma

10.21203/rs.3.rs-219997/v1 ◽

2021 ◽

Author(s):

Zhenyu Zhao ◽

Boxue He ◽

Qidong Cai ◽

Pengfei Zhang ◽

Xiong Peng ◽

...

Keyword(s):

High Risk ◽

Lung Adenocarcinoma ◽

Clinical Application ◽

Risk Group ◽

High Risk Group ◽

Immune Microenvironment ◽

Tumor Mutation Burden ◽

Immune Signature ◽

Immune Infiltration ◽

Mutation Burden

Abstract Background: Lung adenocarcinoma (LUAD) accounts for a majority of cancer-related deaths worldwide annually. A recent study shows that immunotherapy is an effective method of LUAD treatment, and tumor mutation burden (TMB) was associated with the immune microenvironment and affected the immunotherapy. Exploration of the gene signature associated with tumor mutation burden and immune infiltrates in predicting prognosis in lung adenocarcinoma in this study, we explored the correlation of TMB with immune infiltration and prognosis in LUAD.Materials and Methods: In this study, we firstly got mutation data and LUAD RNA-Seq data of the LUAD from The Cancer Genome Atlas (TCGA), and according to the TMB we divided the patients into high/low-TMB levels groups. The gene ontology (GO) pathway enrichment analysis and KOBAS-Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were utilized to explore the molecular function of the differentially expressed genes (DEGs) between the two groups. The function enrichment analyses of DEGs were related to the immune pathways. Then, the ESTIMATE algorithm, CIBERSORT, and ssGSEA analysis were utilized to identify the relationship between TMB subgroups and immune infiltration. According to the results, Venn analysis was utilized to select the immune-related genes in DEGs. Univariate and Lasso Cox proportional hazards regression analyses were performed to construct the signature which positively associated with the immune infiltration and affected the survival. Finally, we verified the correlation between the signature and immune infiltration. Result: The exploration of the immune infiltration suggested that high-TMB subgroups positively associated with the high level of immune infiltration in LUAD patients. According to the TMB-related immune signature, the patients were divided into High/Low-risk groups, and the high-risk group was positively associated with poor prognostic. The results of the PCA analysis confirmed the validity of the signature. We also verified the effectiveness of the signature in GSE30219 and GSE72094 datasets. The ROC curves and C-index suggested the good clinical application of the TMB-related immune signature in LUAD prognosis. Another result suggested that the patients of the high-risk group were positively associated with higher TMB levels, PD-L1expression, and immune infiltration levels.Conclusion: In conclusion, our signature provides potential biomarkers for studying aspects of the TMB in LUAD such as TMB affected immune microenvironment and prognosis. This signature may provide some biomarkers which could improve the biomarkers of PD-L1 immunotherapy response and were inverted for the clinical application of the TMB in LUAD. LUAD male patients with higher TMB-levels and risk scores may benefit from immunotherapy. The high-risk patients along with higher PD-L1 expression of the signature may suitable for immunotherapy and improve their survival by detecting the TMB of LUAD.

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DNA Methylation-Mediated Low Expression of CFTR Stimulates the Progression of Lung Adenocarcinoma

Biochemical Genetics ◽

10.1007/s10528-021-10128-w ◽

2021 ◽

Author(s):

Yue Wang ◽

Lu Tang ◽

Liangliang Yang ◽

Peiyun Lv ◽

Shixiong Mai ◽

...

Keyword(s):

Dna Methylation ◽

Lung Adenocarcinoma ◽

Low Expression

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Identification of a gene set correlated with immune status in ovarian cancer by transcriptome-wide data mining

10.21203/rs.3.rs-17604/v1 ◽

2020 ◽

Author(s):

Lili Fan ◽

Han Lei ◽

Ying Lin ◽

Zhengwei Zhou ◽

Guang Shu ◽

...

Keyword(s):

Ovarian Cancer ◽

Immune Cell ◽

Good Prognosis ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Survival Prognosis ◽

Immune Activity ◽

Gene Set ◽

Immune Infiltration ◽

Keywords Ovarian Cancer

Abstract Background : Ovarian cancer (OC) is a serious tumor disease in gynecology. Many papers have reported that high tumor mutational burden (TMB) can generate many neoantigens to result in a higher degree of tumor immune infiltration, so our study aims to predict the key molecules in OC immunotherapy by combined TMB with immunoactivity-related gene. Method: We divided OC cases into two groups: the low & high TMB group hinged on the somatic mutation data from the Cancer Genome Atlas (TCGA). We also used single-sample gene set enrichment analysis (ssGSEA) scores of immune cell types to conduct unsupervised clustering of OC patients in the TCGA cohort and some of them were defined as the low & high immunity group. Besides, to further understand the function of these genes, we conducted Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, protein-protein interaction network, survival prognosis analysis and immune infiltration analysis. Finally, the effects on prognosis and immunotherapy in OC patients were explored by the Group on Earth Observations verification the patients' responses to immunotherapy. Results: We found that the higher the TMB was associated with the higher OC grades. Moreover, both high TMB and high immunity were significantly correlated with a good prognosis of OC. Then, 14 up-regulated differential expression genes (Up-DEGs) that were closely related to the prognosis of OC patients were screened according to the high TMB group and the high immunity group. Next, pathway analysis revealed that Up-DGEs were mainly involved in immune response and T cell proliferation. Finally, four genes had a good prognosis and were validated in the GEO dataset which included CXCL13, FCRLA, PLA2G2D, and MS4A1. We also identified that four genes had a good prognosis in melanoma patients treated with anti-PD-L1 and anti-CTLA-4 in the TIDE database. Conclusion: High TMB can promote immune cell infiltration and increases immune activity. And our analysis also demonstrated that the higher the TMB, the higher the immune activity, the better the prognosis of OC. Altogether, we found that CXCL13, FCRLA, PLA2G2D, and MS4A1 may be biomarkers for OC immunotherapy. Keywords: ovarian cancer, TMB, immune cells infiltration, survival prognosis.

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Identification and Validation of Immune-Related LncRNA Prognostic Signature for Lung Adenocarcinoma

Frontiers in Genetics ◽

10.3389/fgene.2021.681277 ◽

2021 ◽

Vol 12 ◽

Author(s):

Guomin Wu ◽

Qihao Wang ◽

Ting Zhu ◽

Linhai Fu ◽

Zhupeng Li ◽

...

Keyword(s):

Regression Analysis ◽

Lung Adenocarcinoma ◽

Clinical Features ◽

Cox Regression ◽

Differential Expression Analysis ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Prognostic Signature ◽

Cox Regression Analysis ◽

Immune Infiltration

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.

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