Analysis of the Prognostic Value and Gene Expression Mechanism of SHOX2 in Lung Adenocarcinoma

Background: Detection of SHOX2 methylation has been used to assist in the early diagnosis of lung cancer in many hospitals as SHOX2 may be important in the tumorigenesis of lung cancer. However, there are few studies on the mRNA expression, methylation, and molecular mechanism of SHOX2 in lung cancer. We aimed to explore the role of SHOX2 in lung adenocarcinoma (LUAD).Methods: First, we examined the differential expression of SHOX2 mRNA and methylation in cancerous and normal tissues using databases. Second, we analyzed the relationship between SHOX2 expression and common clinical parameters in LUAD patients. Third, we further explored the methylated level and its specific location of SHOX2 and the mainly factors of SHOX2 gene expression. Finally, we screened the correlatively expressed genes to analyze the pathways from the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes using DAVID.Results: We found that the mRNA expression of SHOX2 was higher in multiple cancers, including LUAD and lung squamous cell carcinoma (LUSC), than in normal tissues. Among LUAD patients, SHOX2 expression was higher in patients of middle–young age, with smoking history, in advanced stages, and with nodal distant metastasis. In addition, our results showed that patients with high expression of SHOX2 are prone to recurrence, poor differentiation, and poor prognosis. Thus, we identified that SHOX2 might be an oncogene for LUAD progression. The main factor influencing the high expression of SHOX2 mRNA may be DNA methylation, followed by copy number variation (CNV), but not by gene mutations in LUAD. Unexpectedly, we found that SHOX2 undergoes hypomethylation in the gene body instead of hypermethylation in the promoter. Additionally, SHOX2 has cross talk in the PI3K–Akt signaling pathway and ECM–receptor interaction.Conclusion:SHOX2 is highly expressed in most cancers. SHOX2 gene expression might be mainly regulated by methylation of its gene body in LUAD, and its high expression or hypomethylation indicates poor differentiation and poor prognosis. SHOX2 could be involved in PI3K–Akt and other important cancer-related signaling pathways to promote tumorigenesis.

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Upregulation of LIMK1 Is Correlated With Poor Prognosis and Immune Infiltrates in Lung Adenocarcinoma

Frontiers in Genetics ◽

10.3389/fgene.2021.671585 ◽

2021 ◽

Vol 12 ◽

Author(s):

Guojun Lu ◽

Ying Zhou ◽

Chenxi Zhang ◽

Yu Zhang

Keyword(s):

Lung Adenocarcinoma ◽

Mrna Expression ◽

Roc Curve ◽

Poor Prognosis ◽

Expression Profiles ◽

Immune Therapy ◽

Functional Enrichment ◽

Normal Tissues ◽

Ppi Networks ◽

Kaplan Meier

BackgroundProtein-coding gene LIM Domain Kinase 1 (LIMK1) is upregulated in various tumors and reported to promote tumor invasion and metastasis. However, the prognostic values of LIMK1 and correlation with immune infiltrates in lung adenocarcinoma are still not understood. Therefore, we evaluated the prognostic role of LIMK1 and its correlation with immune infiltrates in lung adenocarcinoma.MethodsTranscriptional expression profiles of LIMK1 between lung adenocarcinoma tissues and normal tissues were downloaded from the Cancer Genome Atlas (TCGA). The LIMK1 protein expression was assessed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Human Protein Atlas. Receiver operating characteristic (ROC) curve was used to differentiate lung adenocarcinoma from adjacent normal tissues. Kaplan-Meier method was conducted to assess the effect of LIMK1 on survival. Protein-protein interaction (PPI) networks were constructed by the STRING. Functional enrichment analyses were performed using the “ClusterProfiler” package. The relationship between LIMK1 mRNA expression and immune infiltrates was determined by tumor immune estimation resource (TIMER) and tumor-immune system interaction database (TISIDB).ResultsThe expression of LIMK1 in lung adenocarcinoma tissues was significantly upregulated than those in adjacent normal tissues. Increased LIMK1 mRNA expression was associated with lymph node metastases and high TNM stage. The ROC curve analysis showed that with a cutoff level of 4.908, the accuracy, sensitivity, and specificity for LIMK1 differentiate lung adenocarcinoma from adjacent controls were 69.5, 93.2, and 71.9%, respectively. Kaplan-Meier survival analysis showed lung adenocarcinoma patients with high- LIMK1 had a worse prognosis than those with low- LIMK1 (43.1 vs. 55.1 months, P = 0.028). Correlation analysis indicated LIMK1 mRNA expression was correlated with tumor purity and immune infiltrates.ConclusionUpregulated LIMK1 is significantly correlated with poor survival and immune infiltrates in lung adenocarcinoma. Our study suggests that LIMK1 can be used as a biomarker of poor prognosis and potential immune therapy target in lung adenocarcinoma.

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The Expression and Prognostic Significance of the Nicotinic Receptor Cluster on 15q25 about CHRNA5 and PSMA4 mRNA in Lung Adenocarcinoma Utilizing TCGA Datasets

10.21203/rs.2.12982/v1 ◽

2019 ◽

Author(s):

Yuxiu Wang ◽

Xiaolin Wang ◽

Liping Wang ◽

Jianjun Gu ◽

Daohui Gong ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Excision Repair ◽

Prognostic Significance ◽

Enrichment Analysis ◽

High Expression ◽

Smoking History ◽

H1299 Cell ◽

Normal Tissues ◽

Impact On Survival ◽

Base Excision

Abstract Background: To explore the mutations expression and prognostic significance of 15q25 (CHRNA5 and PSMA4) mRNA in lung adenocarcinoma (LAC) based on immunohistochemistry, TCGA and bioinformatics.Methods: Mutations expression on chromosome 15q25 of 576 primary LAC patients was selected. And their survival and gene expression data were extracted from TCGA. The cell experiment about Beas-2b, A549 and H1299 cell lines were done to further prove the CHRNA5 and PSMA4 expression difference between lung cancer and normal cells. Immunohistochemistry data of CHRNA5 and PSMA4 were detected in LAC and normal tissues from 122 patients.Finally, Gene enrichment analysis (GSEA) was used to predict the regulatory genes of CHRNA5 and PSMA4.Results: CHRNA5 and PSMA4 are frequently mutated in the TCGA (CHRNA5, 1.7%; PSMA4, 1.3%).The expression of CHRNA5 and PSMA4 were obviously higher in A549 and H1299 cells. Immunohistochemical staining revealed that the level of CHRNA5 and PSMA4 was considerably higher in LAC group than in normal group. There was a significant association between high expression of CHRNA5 and Smoking History (P=0.011), Smoking History Pack Year Value(P=0.010). Besides, there was a significant correlation between CHRNA5 and PSMA4 expression level and prognosis (P=0.003; P=0.008),and the higher expression, the worse prognosis. GSEA results suggested that CHRNA5 and PSMA4 high expression samples were respectively enriched to cell cycle, base excision repair, oxidative phosphorylation, protein export, aminoacyl tRNA biosynthesis etc.Conclusions: The expression of CHRNA5 and PSMA4 mRNA has a significant impact on survival of LAC, they may be a potential target for treating patients with lung adenocarcinoma.

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The relationship among Girdin DNA methylation, its high expression, and immune infiltration in hepatocellular carcinoma: Clues from in silico analysis

Bioscience Reports ◽

10.1042/bsr20204006 ◽

2021 ◽

Vol 41 (3) ◽

Author(s):

Cheng Zhang ◽

Yang Ke ◽

Xuefen Lei ◽

Xin Liu ◽

Hai Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Dna Methylation ◽

Mrna Expression ◽

Methylation Status ◽

Cancer Genome ◽

High Expression ◽

Gene Body ◽

Immune Infiltration ◽

Normal Tissues ◽

The Relationship

Abstract Objective: The aim of the present study was to explore the relationship among Girdin DNA methylation, its high expression, and immune infiltration in human hepatocellular carcinoma (HCC). Materials and methods: The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and International Cancer Genome Consortium (ICGC) databases were used to compare Girdin mRNA expression between HCC tissues and normal tissues, and determine the relationship between Girdin expression and HCC prognosis. TCGA database was also used to analyze the expression of Girdin and its methylation status, as well as the relationship between Girdin DNA methylation and HCC prognosis. The Tumor IMmune Estimation Resource (TIMER) database was used to explore the correlation between Girdin expression and HCC immune infiltration. Results: Girdin expression was elevated in HCC tissues compared with that in normal tissues. The degree of methylation at cg03188526, a CpG site in the Girdin gene body, was positively correlated with Girdin mRNA expression, while high Girdin expression and cg03188526 hypermethylation were both correlated with poor HCC prognosis. Additionally, HCC tissue with high Girdin expression exhibited abundant immune infiltration, and the high Girdin expression was associated with a worse prognosis in macrophage-enriched HCC specimens. Conclusion: Our findings indicated that Girdin likely functions as an oncogene in HCC and that hypermethylation at cg03188526 in the Girdin gene body may explain the high Girdin expression levels in HCC tissue. Furthermore, we report for the first time that the adverse effects of high Girdin expression in HCC patients may be partially mediated by tumor macrophage infiltration.

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Expression and Prognostic Significance of the Nicotinic Receptor Cluster on 15q25 about CHRNA5 and PSMA4 mRNA in Lung Adenocarcinoma Utilizing TCGA Datasets

10.21203/rs.3.rs-26978/v3 ◽

2020 ◽

Author(s):

Yuxiu Wang ◽

Xiaolin Wang ◽

Liping Wang ◽

Jianjun Gu ◽

Daohui Gong ◽

...

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Excision Repair ◽

Association Studies ◽

Prognostic Significance ◽

Enrichment Analysis ◽

Smoking History ◽

Genome Wide Association Studies ◽

H1299 Cell ◽

Normal Tissues

Abstract Background: Genome-wide association studies of lung cancer have shown a common variation at 15q24-25.1 as a determinant of risk, but the role of specific genes has not been proven. This study aims to explore the expression of mutations and the prognostic significance of 15q25 (CHRNA5 and PSMA4) mRNA in lung adenocarcinoma (LAC) based on immunohistochemistry, TCGA and bioinformatics. Methods: The expression of mutations on chromosome 15q25 of 576 primary LAC patients was selected and survival and gene expression data were extracted from TCGA. The relationship between expression of genes on 15q25 and clinical and prognostic Significance of LAC. An experiment with Beas-2b, A549 and H1299 cell lines was performed to further prove the difference in CHRNA5 and PSMA4 expression between lung cancer and normal cells. Immunohistochemistry data of CHRNA5 and PSMA4 were detected in LAC and normal tissues from 122 patients. Finally, Gene enrichment analysis (GSEA) was conducted to predict the regulatory genes of CHRNA5 and PSMA4. Results: CHRNA5 and PSMA4 are frequently mutated in TCGA (CHRNA5, 1.7%; PSMA4, 1.3%). Besides, the expression of CHRNA5 and PSMA4 was obviously higher in A549 and H1299 cells. And the immunohistochemical staining revealed that the levels of CHRNA5 and PSMA4 were considerably higher in the LAC group than in the normal group. Meanwhile, there was a significant association between high CHRNA5 expression and smoking history (P=0.011), smoking history pack year value (P=0.010). Furthermore, there was a significant correlation between CHRNA5 and PSMA4 expression levels and prognosis (P=0.003; P=0.008), and between higher expression and worse prognosis. GSEA results suggested that between samples with high CHRNA5 and PSMA4 expression were respectively enriched to cell cycle, base excision repair, oxidative phosphorylation, protein export, and aminoacyl tRNA biosynthesis, among others. Conclusions: CHRNA5 and PSMA4 mRNA expression has a significant impact on the clinical and survival of LAC, and they may be a potential target for treating patients with lung adenocarcinoma.

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Multiple cutaneous and haemorrhagic brain metastases as the sentinel presentation of lung adenocarcinoma

BMJ Case Reports ◽

10.1136/bcr-2020-235938 ◽

2020 ◽

Vol 13 (11) ◽

pp. e235938

Author(s):

Pooja Gogia ◽

Jonathan Wallach ◽

Anil Kumar Dhull ◽

Sidharth Bhasin

Keyword(s):

Lung Cancer ◽

Brain Metastases ◽

Lung Adenocarcinoma ◽

Poor Prognosis ◽

Treatment Plan ◽

Performance Status ◽

Memory Loss ◽

Whole Brain Radiotherapy ◽

Smoking History ◽

Cutaneous Lesions

Skin is a relatively uncommon site of metastasis in lung cancer and is associated with a poor prognosis. Although, lung cancer does not uncommonly metastasise to the brain, haemorrhagic brain metastases are rarely reported. In this report, we present a dramatic presentation of a female smoker with a 3-week history of numerous cutaneous lesions over her body and two episodes of transient memory loss. Work-up demonstrated widely metastatic, poorly differentiated lung adenocarcinoma with haemorrhagic brain metastases. She proceeded with whole brain radiotherapy, but her performance status quickly declined afterwards; she succumbed to her malignancy within 6 weeks of presentation. This case presentation demonstrates that, for patients who present with cutaneous masses, especially those aged more than 60 years, and who have extensive smoking history, metastatic lung cancer should remain on the differential diagnosis. Also, the very poor prognosis of multiple metastases may influence medical and social decisions in the patient’s treatment plan.

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Expression and Prognostic Significance of the Nicotinic Receptor Cluster on 15q25 about CHRNA5 and PSMA4 mRNA in Lung Adenocarcinoma Utilizing TCGA Datasets

10.21203/rs.3.rs-26978/v2 ◽

2020 ◽

Author(s):

Yuxiu Wang ◽

Xiaolin Wang ◽

Liping Wang ◽

Jianjun Gu ◽

Daohui Gong ◽

...

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Excision Repair ◽

Association Studies ◽

Prognostic Significance ◽

Enrichment Analysis ◽

Smoking History ◽

Genome Wide Association Studies ◽

H1299 Cell ◽

Normal Tissues

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The Expression and Prognostic Significance of the Nicotinic Receptor Cluster on 15q25 about CHRNA5 and PSMA4 mRNA in Lung Adenocarcinoma Utilizing TCGA Datasets

10.21203/rs.3.rs-26978/v1 ◽

2020 ◽

Author(s):

Yuxiu Wang ◽

Xiaolin Wang ◽

Liping Wang ◽

Jianjun Gu ◽

Daohui Gong ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Excision Repair ◽

Prognostic Significance ◽

Enrichment Analysis ◽

High Expression ◽

Smoking History ◽

H1299 Cell ◽

Normal Tissues ◽

Impact On Survival ◽

Base Excision

Abstract Background To explore the mutations expression and prognostic significance of 15q25 (CHRNA5 and PSMA4) mRNA in lung adenocarcinoma (LAC) based on immunohistochemistry, TCGA and bioinformatics.Methods Mutations expression on chromosome 15q25 of 576 primary LAC patients was selected. And their survival and gene expression data were extracted from TCGA. The cell experiment about Beas-2b, A549 and H1299 cell lines were done to further prove the CHRNA5 and PSMA4 expression difference between lung cancer and normal cells. Immunohistochemistry data of CHRNA5 and PSMA4 were detected in LAC and normal tissues from 122 patients.Finally, Gene enrichment analysis (GSEA) was used to predict the regulatory genes of CHRNA5 and PSMA4.Results CHRNA5 and PSMA4 are frequently mutated in the TCGA (CHRNA5, 1.7%; PSMA4, 1.3%).The expression of CHRNA5 and PSMA4 were obviously higher in A549 and H1299 cells. Immunohistochemical staining revealed that the level of CHRNA5 and PSMA4 was considerably higher in LAC group than in normal group. There was a significant association between high expression of CHRNA5 and Smoking History (P = 0.011), Smoking History Pack Year Value(P = 0.010). Besides, there was a significant correlation between CHRNA5 and PSMA4 expression level and prognosis (P = 0.003; P = 0.008),and the higher expression, the worse prognosis. GSEA results suggested that CHRNA5 and PSMA4 high expression samples were respectively enriched to cell cycle, base excision repair, oxidative phosphorylation, protein export, aminoacyl tRNA biosynthesis etc.Conclusions The expression of CHRNA5 and PSMA4 mRNA has a significant impact on survival of LAC, they may be a potential target for treating patients with lung adenocarcinoma.

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High expression of Stabilin-2 predicts poor prognosis in non-small-cell lung cancer

Bioengineered ◽

10.1080/21655979.2021.1943109 ◽

2021 ◽

Vol 12 (1) ◽

pp. 3426-3433

Author(s):

Juanjuan Yong ◽

Liyun Huang ◽

Gengbiao Chen ◽

Xiaoya Luo ◽

Hui Chen ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Poor Prognosis ◽

Small Cell ◽

High Expression ◽

Small Cell Lung

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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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EGFR and hTERT Expression as a Diagnostic Approach for Non-small Cell Lung Cancer in High Risk Groups

Biomarkers in Cancer ◽

10.4137/bic.s3383 ◽

2010 ◽

Vol 2 ◽

pp. BIC.S3383 ◽

Cited By ~ 2

Author(s):

Radostina Cherneva ◽

Ognian Georgiev ◽

Ivanka Dimova ◽

Blaga Rukova ◽

Danail Petrov ◽

...

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

High Risk ◽

Small Cell Lung Cancer ◽

Mrna Expression ◽

Small Cell ◽

Htert Mrna ◽

Small Cell Lung ◽

The Mean ◽

Htert Mrna Expression

Objective The early detection of NSCLC is of importance because it provides chances for better outcomes. The aim of the study was to explore the clinical utility of EGFR and hTERT mRNA expression as markers for diagnosis of NSCLC. Methods EGFR and hTERT mRNA were quantified by quantative reverse transcription real time polymerase chain reaction in plasma of 45 non-small cell lung cancer (NSCLC) and 40 chronic obstructive pulmonary disease (COPD) patients, selected by certain spirometric characteristics that made them at high risk of developing lung cancer in future. Results The gene expression level of each gene was calculated and given as a relative quantity–-RQ. EGFR gene expression was found in all lung cancer patients. The mean level of expression was RQ = 29.39. hTERT mRNA could be detected in 88% of patients. The mean expression ratio in them was RQ = 17.31. Only 50% of the high risk patients turned to be positive for EGFR. The level of their expression was RQ = 2.09. The plasma levels of hTERT could be detected in 17 (42.5%) patients of the high risk COPD group. Their mean level of expression was RQ = 1.02. A statistically significant difference in EGFR and hTERT mRNA expression could be observed between the two groups of patients–-p = 0.0001. Conclusion EGFR and hTERT mRNA are potential markers for lung cancer diagnosis, whose clinical importance should be replicated in a larger cohort of patients.

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