scholarly journals Transcriptome Based Estrogen Related Genes Biomarkers for Diagnosis and Prognosis in Non-small Cell Lung Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Sinong Jia ◽  
Lei Li ◽  
Li Xie ◽  
Weituo Zhang ◽  
Tengteng Zhu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Estrogen Receptor ◽  
Lung Squamous Cell Carcinoma ◽  
Public Health Problem ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Estrogen Signaling ◽  
Global Public Health ◽  
Normal Tissues ◽  
Tumor Tissues

BackgroundLung cancer is the tumor with the highest morbidity and mortality, and has become a global public health problem. The incidence of lung cancer in men has declined in some countries and regions, while the incidence of lung cancer in women has been slowly increasing. Therefore, the aim is to explore whether estrogen-related genes are associated with the incidence and prognosis of lung cancer.MethodsWe obtained all estrogen receptor genes and estrogen signaling pathway genes in The Cancer Genome Atlas (TCGA), and then compared the expression of each gene in tumor tissues and adjacent normal tissues for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) separately. Survival analysis was performed of the differentially expressed genes in LUAD and LUSC patients separately. The diagnostic and prognostic values of the candidate genes were validated in the Gene Expression Omnibus (GEO) datasets.ResultsWe found 5 estrogen receptor genes and 66 estrogen pathway genes in TCGA. A total of 50 genes were differently expressed between tumor tissues and adjacent normal tissues and 6 of the 50 genes were related to the prognosis of LUAD in TCGA. 56 genes were differently expressed between tumor tissues and adjacent normal tissues and none of the 56 genes was related to the prognosis of LUSC in TCGA. GEO datasets validated that the 6 genes (SHC1, FKBP4, NRAS, PRKCD, KRAS, ADCY9) had different expression between tumor tissues and adjacent normal tissues in LUAD, and 3 genes (FKBP4, KRAS, ADCY9) were related to the prognosis of LUAD.ConclusionsThe expressions of FKBP4 and ADCY9 are related to the pathogenesis and prognosis of LUAD. FKBP4 and ADCY9 may serve as biomarkers in LUAD screening and prognosis prediction in clinical settings.

scholarly journals UBE2D1 RNA Expression Was an Independent Unfavorable Prognostic Indicator in Lung Adenocarcinoma, but Not in Lung Squamous Cell Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Liyan Hou ◽  
Yingbo Li ◽  
Ying Wang ◽  
Dongqiang Xu ◽  
Hailing Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Survival Data ◽  
Lung Squamous Cell Carcinoma ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Rna Expression

In this study, we investigated the potential prognostic value of ubiquitin-conjugating enzyme E2D1 (UBE2D1) RNA expression in different histological subtypes of non-small-cell lung cancer (NSCLC). A retrospective study was performed by using molecular, clinicopathological, and survival data in the Cancer Genome Atlas (TCGA)—Lung Cancer. Results showed that both lung adenocarcinoma (LUAD) (N=514) and lung squamous cell carcinoma (LUSC) (N=502) tissues had significantly elevated UBE2D1 RNA expression compared to the normal tissues (p<0.001 and p=0.036, respectively). UBE2D1 RNA expression was significantly higher in LUAD than in LUSC tissues. Increased UBE2D1 RNA expression was independently associated with shorter OS (HR: 1.359, 95% CI: 1.031–1.791, p=0.029) and RFS (HR: 1.842, 95% CI: 1.353–2.508, p<0.001) in LUAD patients, but not in LUSC patients. DNA amplification was common in LUAD patients (88/551, 16.0%) and was associated with significantly upregulated UBE2D1 RNA expression. Based on these findings, we infer that UBE2D1 RNA expression might only serve as an independent prognostic indicator of unfavorable OS and RFS in LUAD, but not in LUSC.

scholarly journals The expression characteristics and prognostic roles of autophagy-related genes in gastric cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10814
Author(s):  
Mengya Wang ◽  
Jingjing Jing ◽  
Hao Li ◽  
Jingwei Liu ◽  
Yuan Yuan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Factors ◽  
Differential Expression Analysis ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Normal Tissues ◽  
Genes Expression ◽  
Expression Characteristics ◽  
Cellular Components

Background Autophagy is an evolutionally highly conserved process, accompanied by the dynamic changes of various molecules, which is necessary for the orderly degradation and recycling of cellular components. The aim of the study was to identify the role of autophagy-related (ATG) genes in the occurrence and development of gastric cancer (GC). Methods Data from Oncomine dataset was used for the differential expression analysis between cancer and normal tissues. The association of ATG genes expression with clinicopathologic indicators was evaluated by The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. Moreover, using the TCGA datasets, the prognostic role of ATG genes was assessed. A nomogram was further built to assess the independent prognostic factors. Results The expression of autophagy-related genes AMBRA1, ATG4B, ATG7, ATG10, ATG12, ATG16L2, GABARAPL2, GABARAPL1, ULK4 and WIPI2 showed differences between cancer and normal tissues. After verification, ATG14 and ATG4D were significantly associated with TNM stage. ATG9A, ATG2A, and ATG4D were associated with T stage. VMP1 and ATG4A were low-expressed in patients without lymph node metastasis. No gene in autophagy pathway was associated with M stage. Further multivariate analysis suggested that ATG4D and MAP1LC3C were independent prognostic factors for GC. The C-index of nomogram was 0.676 and the 95% CI was 0.628 to 0.724. Conclusion Our study provided a comprehensive illustration of ATG genes expression characteristics in GC. Abnormal expressions of the ubiquitin-like conjugated system in ATG genes plays a key role in the occurrence of GC. ATG8/LC3 sub-system may play an important role in development and clinical outcome of GC. In the future, it is necessary to further elucidate the alterations of specific ATG8/LC3 forms in order to provide insights for the discovery, diagnosis, or targeting for GC.

scholarly journals DNASE1L3 as a Novel Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma Based on Data Mining

2021 ◽  
Vol 12 ◽  
Author(s):  
Jianlin Chen ◽  
Junping Ding ◽  
Wenjie Huang ◽  
Lin Sun ◽  
Jinping Chen ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Prognostic Biomarker ◽  
Function Analysis ◽  
Mrna Level ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Diagnostic Efficiency ◽  
Protein Levels ◽  
Normal Tissues

Previous researches have highlighted that low-expressing deoxyribonuclease1-like 3 (DNASE1L3) may play a role as a potential prognostic biomarker in several cancers. However, the diagnosis and prognosis roles of DNASE1L3 gene in lung adenocarcinoma (LUAD) remain largely unknown. This research aimed to explore the diagnosis value, prognostic value, and potential oncogenic roles of DNASE1L3 in LUAD. We performed bioinformatics analysis on LUAD datasets downloaded from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus), and jointly analyzed with various online databases. We found that both the mRNA and protein levels of DNASE1L3 in patients with LUAD were noticeably lower than that in normal tissues. Low DNASE1L3 expression was significantly associated with higher pathological stages, T stages, and poor prognosis in LUAD cohorts. Multivariate analysis revealed that DNASE1L3 was an independent factor affecting overall survival (HR = 0.680, p = 0.027). Moreover, decreased DNASE1L3 showed strong diagnostic efficiency for LUAD. Results indicated that the mRNA level of DNASE1L3 was positively correlated with the infiltration of various immune cells, immune checkpoints in LUAD, especially with some m6A methylation regulators. In addition, enrichment function analysis revealed that the co-expressed genes may participate in the process of intercellular signal transduction and transmission. GSEA indicated that DNASE1L3 was positively related to G protein-coupled receptor ligand biding (NES = 1.738; P adjust = 0.044; FDR = 0.033) and G alpha (i) signaling events (NES = 1.635; P adjust = 0.044; FDR = 0.033). Our results demonstrated that decreased DNASE1L3 may serve as a novel diagnostic and prognostic biomarker associating with immune infiltrates in lung adenocarcinoma.

scholarly journals Increased GOLM1 Expression Independently Predicts Unfavorable Overall Survival and Recurrence-Free Survival in Lung Adenocarcinoma

2018 ◽  
Vol 25 (1) ◽  
pp. 107327481877800 ◽  
Author(s):  
Xi Liu ◽  
Lei Chen ◽  
Tao Zhang
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Survival Data ◽  
Methylation Status ◽  
Lung Squamous Cell Carcinoma ◽  
Prognostic Indicator ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Recurrence Free Survival ◽  
Free Survival

Golgi membrane protein 1 (GOLM1) is a transmembrane glycoprotein of the Golgi cisternae, which is implicated in carcinogenesis of multiple types of cancer. In this study, using data from the Gene Expression Omnibus and The Cancer Genome Atlas, we compared the expression of GOLM1 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) and studied its prognostic value in terms of overall survival (OS) and recurrence-free survival (RFS) in these 2 subtypes of non-small cell lung cancer (NSCLC). Results showed that GOLM1 was significantly upregulated in both LUAD and LUSC tissues compared to the normal controls. However, GOLM1 expression was higher in LUAD tissues than in LUSC tissues. More importantly, using over 10 years’ survival data from 502 patients with LUAD and 494 patients with LUSC, we found that high GOLM1 expression was associated with unfavorable OS and RFS in patients with LUAD, but not in patients with LUSC. The following univariate and multivariate analyses confirmed that increased GOLM1 expression was an independent prognostic indicator of poor OS (hazard ratio [HR]: 1.30, 95% confidence interval [CI]: 1.11-1.54, P = .002) and RFS (HR: 1.37, 95% CI: 1.14-1.64, P = .001) in patients with LUAD. Of 511 cases with LUAD, 248 (48.5%) had heterozygous loss (−1), while 28 (5.5%) of 511 cases with LUAD had low-level copy gain (+1). In addition, we also found that the methylation status of 1 CpG site (chr9: 88,694,942-88,694,944) showed a weak negative correlation with GOLM1 expression (Pearson r = −0.25). Based on these findings, we infer that GOLM1 might serve as a valuable prognostic biomarker in LUAD, but not in LUSC. In addition, DNA copy number alterations and methylation might be 2 important mechanisms of dysregulated GOLM1 in LUAD.

scholarly journals Deciphering N6-Methyladenosine-Related Genes Signature to Predict Survival in Lung Adenocarcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Jie Zhu ◽  
Min Wang ◽  
Daixing Hu
Keyword(s):  
Lung Adenocarcinoma ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Consensus Clustering ◽  
Lasso Regression ◽  
Gene Expressions ◽  
Tumor Tissues ◽  
Cancer Genome Atlas ◽  
Selection Operator ◽  
Cox Analysis

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related death. Among these, lung adenocarcinoma (LUAD) accounts for most cases. Due to the improvement of precision medicine based on molecular characterization, the treatment of LUAD underwent significant changes. With these changes, the prognosis of LUAD becomes diverse. N6-methyladenosine (m6A) is the most predominant modification in mRNAs, which has been a research hotspot in the field of oncology. Nevertheless, little has been studied to reveal the correlations between the m6A-related genes and prognosis in LUAD. Thus, we conducted a comprehensive analysis of m6A-related gene expressions in LUAD patients based on The Cancer Genome Atlas (TCGA) database by revealing their relationship with prognosis. Different expressions of the m6A-related genes in tumor tissues and non-tumor tissues were confirmed. Furthermore, their relationship with prognosis was studied via Consensus Clustering Analysis, Principal Components Analysis (PCA), and Least Absolute Shrinkage and Selection Operator (LASSO) Regression. Based on the above analyses, a m6A-based signature to predict the overall survival (OS) in LUAD was successfully established. Among the 479 cases, we found that most of the m6A-related genes were differentially expressed between tumor and non-tumor tissues. Six genes, HNRNPC, METTL3, YTHDC2, KIAA1429, ALKBH5, and YTHDF1 were screened to build a risk scoring signature, which is strongly related to the clinical features pathological stages (p<0.05), M stages (p<0.05), T stages (p < 0.05), gender (p=0.04), and survival outcome (p=0.02). Multivariate Cox analysis indicated that risk value could be used as an independent prognostic factor, revealing that the m6A-related genes signature has great predictive value. Its efficacy was also validated by data from the Gene Expression Omnibus (GEO) database.

scholarly journals Differentially Expressed miRNAs in Tumor, Adjacent, and Normal Tissues of Lung Adenocarcinoma

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Fei Tian ◽  
Rui Li ◽  
Zhenzhu Chen ◽  
Yanting Shen ◽  
Jiafeng Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Target Genes ◽  
Expression Profiles ◽  
Major Type ◽  
Regulatory Pathways ◽  
Normal Tissues ◽  
Qrt Pcr ◽  
Diagnosis And Prognosis ◽  
Tumor Tissues

Lung cancer is the leading cause of cancer deaths. Non-small-cell lung cancer (NSCLC) is the major type of lung cancer. The aim of this study was to characterize the expression profiles of miRNAs in adenocarcinoma (AC), one major subtype of NSCLC. In this study, the miRNAs were detected in normal, adjacent, and tumor tissues by next-generation sequencing. Then the expression levels of differential miRNAs were quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In the results, 259, 401, and 389 miRNAs were detected in tumor, adjacent, and normal tissues of pooled AC samples, respectively. In addition, for the first time we have found that miR-21-5p and miR-196a-5p were gradually upregulated from normal to adjacent to tumor tissues; miR-218-5p was gradually downregulated with 2-fold or greater change in AC tissues. These 3 miRNAs were validated by qRT-PCR. Lastly, we predicted target genes of these 3 miRNAs and enriched the potential functions and regulatory pathways. The aberrant miR-21-5p, miR-196a-5p, and miR-218-5p may become biomarkers for diagnosis and prognosis of lung adenocarcinoma. This research may be useful for lung adenocarcinoma diagnosis and the study of pathology in lung cancer.

scholarly journals High expression levels of pyrimidine metabolic rate–limiting enzymes are adverse prognostic factors in lung adenocarcinoma: a study based on The Cancer Genome Atlas and Gene Expression Omnibus datasets

2020 ◽  
Vol 16 (3) ◽  
pp. 347-366 ◽  
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Ji Zhang ◽  
Hua Cao
Keyword(s):  
Lung Cancer ◽  
Metabolic Rate ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Pyrimidine Metabolism ◽  
Expression Levels ◽  
Cancer Genome Atlas ◽  
Rate Limiting ◽  
Genome Atlas

Abstract Reprogramming of metabolism is described in many types of cancer and is associated with the clinical outcomes. However, the prognostic significance of pyrimidine metabolism signaling pathway in lung adenocarcinoma (LUAD) is unclear. Using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets, we found that the pyrimidine metabolism signaling pathway was significantly enriched in LUAD. Compared with normal lung tissues, the pyrimidine metabolic rate–limiting enzymes were highly expressed in lung tumor tissues. The high expression levels of pyrimidine metabolic–rate limiting enzymes were associated with unfavorable prognosis. However, purinergic receptors P2RX1, P2RX7, P2RY12, P2RY13, and P2RY14 were relatively downregulated in lung cancer tissues and were associated with favorable prognosis. Moreover, we found that hypo-DNA methylation, DNA amplification, and TP53 mutation were contributing to the high expression levels of pyrimidine metabolic rate–limiting enzymes in lung cancer cells. Furthermore, combined pyrimidine metabolic rate–limiting enzymes had significant prognostic effects in LUAD. Comprehensively, the pyrimidine metabolic rate–limiting enzymes were highly expressed in bladder cancer, breast cancer, colon cancer, liver cancer, and stomach cancer. And the high expression levels of pyrimidine metabolic rate–limiting enzymes were associated with unfavorable prognosis in liver cancer. Overall, our results suggested the mRNA levels of pyrimidine metabolic rate–limiting enzymes CAD, DTYMK, RRM1, RRM2, TK1, TYMS, UCK2, NR5C2, and TK2 were predictive of lung cancer as well as other cancers.

scholarly journals Downregulated SPINK4 is associated with poor survival in colorectal cancer

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaojie Wang ◽  
Qian Yu ◽  
Waleed M. Ghareeb ◽  
Yiyi Zhang ◽  
Xingrong Lu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Expression Data ◽  
Poor Survival ◽  
Protein Levels ◽  
Normal Tissues ◽  
Human Protein Atlas ◽  
Cancer Genome Atlas ◽  
Independent Indicator

Abstract Background SPINK4 is known as a gastrointestinal peptide in the gastrointestinal tract and is abundantly expressed in human goblet cells. The clinical significance of SPINK4 in colorectal cancer (CRC) is largely unknown. Methods We retrieved the expression data of 1168 CRC patients from 3 Gene Expression Omnibus (GEO) datasets (GSE24551, GSE39582, GSE32323) and The Cancer Genome Atlas (TCGA) to compare the expression level of SPINK4 between CRC tissues and normal colorectal tissues and to evaluate its value in predicting the survival of CRC patients. At the protein level, these results were further confirmed by data mining in the Human Protein Atlas and by immunohistochemical staining of samples from 81 CRC cases in our own center. Results SPINK4 expression was downregulated in CRC compared with that in normal tissues, and decreased SPINK4 expression at both the mRNA and protein levels was associated with poor prognosis in CRC patients from all 3 GEO datasets, the TCGA database and our cohort. Additionally, lower SPINK4 expression was significantly related to higher TNM stage. Moreover, in multivariate regression, SPINK4 was confirmed as an independent indicator of poor survival in CRC patients in all databases and in our own cohort. Conclusions We concluded that reduced expression of SPINK4 relates to poor survival in CRC, functioning as a novel indicator.

Expression profile and potential regulatory pathways of SFTPA1 in human tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15675-e15675
Author(s):  
Lu Yuan ◽  
Mi Yang ◽  
Xixi Wu ◽  
Wenqi Huang ◽  
Yuting Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Expression Profile ◽  
Critical Role ◽  
Human Tumor ◽  
Lung Squamous Cell Carcinoma ◽  
Surfactant Protein ◽  
Functional Heterogeneity ◽  
Regulatory Pathways ◽  
Tumor Tissues ◽  
Potential Biomarker

e15675 Background: Pulmonary surfactant protein A1(SFTPA1) plays a critical role in maintaining lung tissue homeostasis and its disruption could cause lung diseases and even lung cancer. Despite the finding that SFTPA1 is a potential biomarker for lung cancer, the expression profile and molecular mechanism of SFTPA1 in pan-cancer remain unclear. Methods: The expression of SFTPA1 in BALB/c mice, human normal tissues and human tumor tissues were explored by immunohistochemistry assay. The prognostic values were evaluated by Kaplan-Meier Plotter Database Analysis. Principal components analysis and GO and KEGG pathway enrichment analyses were exerted to identify the functional heterogeneity of SFTPA1 in various tumors. Multiple databases were used to analyze immune infiltrates and regulation networks of SFTPA1. Results: This study described the expression profile of SFTPA1 in various organs and tissues of BALB/c mice and various types of human tumor tissues. Interestingly, we found the expression level of SFTPA1 mRNA was associated with different prognosis in different cancers, even in Lung adenocarcinoma(LUAD) and Lung squamous cell carcinoma(LUSC). The further analysis confirmed a functional heterogeneity of SFTPA1 across diverse cancer types. Significantly, SFTPA1 might regulate tumor microenvironment by affecting the polarization of M2 macrophages in LUAD and LUSC. Furthermore, we found the has-miR-3200-3p-HNF1B-SFTPA1 network was a potential upstream regulatory mechanism of SFTPA1 in LUSC. Conclusions: Our study elaborated expression profile and potential regulatory pathways of SFTPA1 in human solid cancers, and might provide a potential immune infiltration biomarker for lung cancer.

scholarly journals Comprehensive analysis of PD-L1 expression, tumor-infiltrating lymphocytes, and tumor microenvironment in LUAD: differences between Asians and Caucasians

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Fenglong Bie ◽  
He Tian ◽  
Nan Sun ◽  
Ruochuan Zang ◽  
Moyan Zhang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Infiltrating Lymphocytes ◽  
The Cancer Genome Atlas ◽  
Normal Tissues ◽  
Asian Patients ◽  
Expression Of Genes ◽  
Tumor Tissues ◽  
Significant Difference ◽  
Cancer Genome Atlas ◽  
Infiltrating Lymphocytes

Abstract Backgrounds The characteristics of programmed cell death protein-1 (PD-L1) expression, tumor-infiltrating lymphocytes (TILs), and tumor microenvironment (TME) in lung adenocarcinoma (LUAD) patients are closely related to immunotherapy, and there are differences between Asians and Caucasians. Methods Acquire the transcriptome data of the Cancer Genome Atlas and Chinese LUAD patients. R software was used to analyze the differential expression of genes, prognosis, and gene function. Use CIBERSORT for TIL-related analysis and ESTIMATE for TME-related analysis. Results The expression of PD-L1 in tumor tissues of Caucasian LUAD patients was lower than that in normal tissues, while there was no significant difference in Asians. There was no statistical difference between PD-L1 expression and prognosis. The composition of TILs between Caucasian and Asian LUAD patients was quite different. There was no correlation between TILs and prognosis in Caucasians. However, the higher content of resting mast cells indicated a better prognosis in Asians. The Caucasian patients with higher immune and estimate scores had a better prognosis (p = 0.021, p = 0.025). However, the Asian patients with a higher estimate score had a worse prognosis (p = 0.024). The high expression of COL5A2 (p = 0.046, p = 0.027) and NOX4 (p = 0.020, p = 0.019) were both associated with the poor prognosis in Caucasians and Asians. Conclusion There are many differences in the characteristics of PD-L1 expression, TILs, and TME between Caucasian and Asian LUAD patients. This provides a certain hint for the selection of specific immunotherapy strategies separately for Caucasian and Asian LUAD patients.

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