Low-Level Expression of MTUS1 Is Associated with Poor Survival in Patients with Lung Adenocarcinoma

Microtubule-associated tumor suppressor 1 (MTUS1) is thought to be downregulated in arious human cancers, which suggests its role as a tumor suppressor. This study investigated the clinicopathological significance of MTUS1 expression in lung adenocarcinoma. Tissue microarray blocks consisting of 161 cases were constructed, and immunohistochemical staining was used to assess MTUS1 expression. Correlations of MTUS1 expression and clinicopathological parameters were analyzed. In addition, we used public databases and performed bioinformatics analysis. Low level of MTUS1 was significantly associated with higher clinical stage (p = 0.006), higher tumor stage (p = 0.044), lymph node metastasis (p = 0.01), worse histologic grade (p = 0.007), lymphovascular invasion (p = 0.014), and higher Ki-67 proliferation index (p < 0.001). Patients with low MTUS1 expression also showed shorter disease-free survival (p = 0.002) and cancer-specific survival (p = 0.006). Analysis of data from the Cancer Genome Atlas confirmed that the mRNA expression of MTUS1 in lung adenocarcinoma was significantly lower than that of normal lung tissue (p = 0.02), and patients with decreased MTUS1 expression showed significantly shorter overall survival (p = 0.008). These results suggest that MTUS1 may be a potential biomarker for predicting clinical outcomes in lung adenocarcinoma patients.

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Increased STIP1 and Hsp90 Correlate with Progression and Prognosis of Lung Adenocarcinoma

10.21203/rs.3.rs-226260/v1 ◽

2021 ◽

Author(s):

Biaoxue Rong ◽

Youwen Zhang ◽

Junye Wang ◽

Shucheng Ye ◽

Maoqing Guo ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Malignant Tumors ◽

Clinical Stage ◽

A549 Cells ◽

Biological Behavior ◽

Prognostic Indicators ◽

Normal Lung ◽

Clinicopathological Parameters ◽

Strong Positive Correlation ◽

Advanced Clinical Stage

Abstract Background: Stress-inducible phosphoprotein 1 (STIP1) and heat shock protein 90 (Hsp90) have been found to be correlated with malignant tumors. The aim of this investigation was to study the relationship between their expressions and lung adenocarcinoma (LAC). Methods: The expressions of STIP1and Hsp90 in LAC cells and tissues were tested by immunohistochemistry and western blot; the correlation between their expressions and clinicopathological parameters of LAC was analyzed by survival analysisand multiple regression analysis. Results: Expressions of STIP1 and Hsp90 were higher in A549 cells and LAC tissues than that in 16 human bronchial epithelial cells (16HBE cells) (P<0.05) and adjacent normal lung tissues (P < 0.05). The expression of STIP1 and Hsp90 in LAC showed a strong positive correlation (P < 0.05) and significantly correlated with lymph node metastasis (P < 0.05), advanced clinical stage (P < 0.05) and shorter survival (P < 0.05) of LAC. Conclusions: Increased expressions of STIP1 and Hsp90 were closely related to malignant biological behavior of LAC, suggesting that they could be used as potential biomarkers and prognostic indicators for LAC.

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Elevated Glutathione Peroxidase 2 Expression Promotes Cisplatin Resistance in Lung Adenocarcinoma

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/7370157 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

He Du ◽

Bi Chen ◽

Nan-Lin Jiao ◽

Yan-Hua Liu ◽

San-Yuan Sun ◽

...

Keyword(s):

Energy Metabolism ◽

Glutathione Peroxidase ◽

Lung Adenocarcinoma ◽

Cell Line ◽

A549 Cells ◽

Disease Free Survival ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Normal Lung

The aim of this study was to explore the roles of GPX2, a member of the glutathione peroxidase family (GPXs, GSH-Px), in cisplatin (DDP) resistance in lung adenocarcinoma (LUAD). GPX2 was found to be the most significantly upregulated gene in a DDP-resistant A549/DDP cell line compared with the parental A549 cell line by RNA sequencing. The knockdown of GPX2 expression in A549/DDP cells inhibited cell proliferation in vitro and in vivo, decreased the IC50 values of DDP, induced apoptosis, inhibited the activities of GSH-Px and superoxide dismutase (SOD), inhibited ATP production and glucose uptake, and increased malondialdehyde (MDA) and reactive oxygen species (ROS) production; while GPX2 overexpression in A549 cells resulted in the opposite effects. Using gene set enrichment analysis (GSEA), we found that GPX2 may be involved in DDP resistance through mediating drug metabolism, the cell cycle, DNA repair and energy metabolism, and the regulation of an ATP-binding cassette (ABC) transporters member ABCB6, which is one of the hallmark genes in glycolysis. Moreover, immunohistochemistry revealed that GPX2 was upregulated in 58.6% (89/152) of LUAD cases, and elevated GPX2 expression was correlated with high expression of ABCB6, high 18-fluorodeoxyglucose (18F-FDG) uptake, and adverse disease-free survival (DFS) in our cohort. The Cancer Genome Atlas (TCGA) data also indicated that GPX2 expression was higher in LUAD than it was in normal lung tissues, and the mRNA expression levels of GPX2 and ABCB6 were positively correlated. In conclusion, our study demonstrates that GPX2 acts as oncogene in LUAD and promotes DDP resistance by regulating oxidative stress and energy metabolism.

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Co-overexpression of STIP1 and Hsp90 correlates with progression and prognosis of lung adenocarcinoma

10.21203/rs.2.13680/v2 ◽

2020 ◽

Author(s):

Youwen Zhang ◽

Junye Wang ◽

Shucheng Ye ◽

Maoqing Guo ◽

Shenghua Jiang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Malignant Tumors ◽

Clinical Stage ◽

A549 Cells ◽

Biological Behavior ◽

Prognostic Indicators ◽

Normal Lung ◽

Clinicopathological Parameters ◽

Strong Positive Correlation ◽

Advanced Clinical Stage

Abstract Background: Stress-inducible phosphoprotein 1 (STIP1) and heat shock protein 90 (Hsp90) have been found to be correlated with malignant tumors. The aim of this study was to analyze the relationship between their expressions and lung adenocarcinoma (LAC). Methods: The expressions of STIP1 and Hsp90 in LAC cells and tissues were tested by immunohistochemistry and western blot; the correlation between their expressions and clinicopathological parameters of LAC was analyzed by survival analysis and multiple regression analysis. Results: The expressions of STIP1 and Hsp90 were higher in A549 cells and LAC tissues than that in 16 human bronchial epithelial cells (16HBE cells) (P < 0.05) and cancer-adjacent normal lung tissues (P < 0.05). The expressions of STIP1 and Hsp90 in LAC showed a strong positive correlation (P < 0.05) and the increased expressions of STIP1 and Hsp90 significantly correlated with lymph node metastasis (P < 0.05), advanced clinical stage (P < 0.05) and shorter survival (P < 0.05) of LAC. Conclusions: The increased expressions of STIP1 and Hsp90 were closely related to malignant biological behavior of LAC, indicating that they could be used as the potential biomarkers and prognostic indicators for LAC.

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Increased STIP1 and Hsp90 correlate with progression and prognosis of lung adenocarcinoma

10.21203/rs.2.13680/v1 ◽

2019 ◽

Author(s):

Youwen Zhang ◽

Junye Wang ◽

Shucheng Ye ◽

Maoqing Guo ◽

Shenghua Jiang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Malignant Tumors ◽

Clinical Stage ◽

A549 Cells ◽

Biological Behavior ◽

Prognostic Indicators ◽

Normal Lung ◽

Clinicopathological Parameters ◽

Strong Positive Correlation ◽

Advanced Clinical Stage

Abstract Background: Stress-inducible phosphoprotein 1 (STIP1) and heat shock protein 90 (Hsp90) have been found to be correlated with malignant tumors. The aim of this investigation was to study the relationship between their expressions and lung adenocarcinoma (LAC). Methods: The expressions of STIP1 and Hsp90 in LAC cells and tissues were tested by immunohistochemistry and western blot; the correlation between their expressions and clinicopathological parameters of LAC was analyzed by survival analysis and multiple regression analysis. Results: Expressions of STIP1 and Hsp90 were higher in A549 cells and LAC tissues than that in 16 human bronchial epithelial cells (16HBE cells) (P < 0.05) and adjacent normal lung tissues (P < 0.05). The expression of STIP1 and Hsp90 in LAC showed a strong positive correlation (P < 0.05) and significantly correlated with lymph node metastasis (P < 0.05), advanced clinical stage (P < 0.05) and shorter survival (P < 0.05) of LAC. Conclusions: Increased expressions of STIP1 and Hsp90 were closely related to malignant biological behavior of LAC, suggesting that they could be used as potential biomarkers and prognostic indicators for LAC.

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FADS1 is a Prognostic Biomarker in Bladder Cancer: A Study Based on TCGA Data

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666200925104911 ◽

2020 ◽

Vol 23 ◽

Author(s):

Ying Lu ◽

Jing Shao ◽

Xu Shu ◽

Yaofei Jiang ◽

Jianfang Rong ◽

...

Keyword(s):

Bladder Cancer ◽

Histological Grade ◽

Clinical Stage ◽

Fatty Acid Desaturase ◽

Clinical Information ◽

The Cancer Genome Atlas ◽

Cancer Prognosis ◽

Normal Tissues ◽

Potential Biomarker ◽

T Classification

Aim and Objective: Fatty acid desaturase 1 (FADS1) has been reported to be a potential biomarker in various cancers. However, no study has explored the relationship between FADS1 expression and bladder cancer. Our study aimed to investigate the role of FADS1 in bladder cancer prognosis via The Cancer Genome Atlas (TCGA). Materials and Methods: RNA-Seq expression of 414 tumor tissues and 19 paired normal tissues, as well as corresponding clinical data, were downloaded from TCGA database. Two cancer cases were excluded due to a lack of clinical information. The association between FADS1 and the clinicopathological features of bladder cancer was analyzed. This study was conducted in October of 2019 in China. Results: The high expression of FADS1 in bladder cancer was significantly related to histological grade (OR = 0.155 for low vs. high), clinical stage (OR=2.074 for III or IV vs. I or II), T classification (OR=2.326 for T3 or T4 vs. T1 or T2), lymphatic metastasis (OR=1.923 for N1 or N2 or N3 vs. N0) and distant metastasis (OR=4.883 for yes vs. no) (all p-values <0.05). Bladder cancer with high FADS1 levels was related to a worse prognosis than bladder cancer with low FADS1 levels (p= 1.626*10-5 ), according to median expression value 3.622. FADS1 was an independent factor of overall survival in bladder cancer, with a hazard ratio of 1.048 (95%CI: 1.020–1.077, p = 0.001). Conclusions: Increased FADS1 expression in bladder cancer is associated with advanced clinical pathological features and may be a potential biomarker for poor 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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Erythropoietin Receptor is a Risk Factor for Prognosis: A Potential Biomarker in Lung Adenocarcinoma

10.21203/rs.3.rs-1211017/v1 ◽

2022 ◽

Author(s):

Ya-Jing Zhang ◽

Sen-Yu Wang ◽

Song-Tao Han ◽

Yao-Yao Huang ◽

Yang-Chun Feng

Keyword(s):

Lung Adenocarcinoma ◽

Gene Mutations ◽

Predictive Ability ◽

Erythropoietin Receptor ◽

Immunohistochemical Method ◽

Normal Lung ◽

Mrna Levels ◽

Protein Levels ◽

Potential Biomarker ◽

Epor Expression

Abstract Background: Lung cancer has the highest mortality rate of all cancers, and LUAD's survival rate is particularly poor. Erythropoietin receptor (EPOR) is a member of the cytokine class I receptor family and can be detected in cancers such as lung adenocarcinoma (LUAD), however, the expression levels and prognostic value of EPOR in LUAD are still unclear.Methods: Multiple bioinformatics databases such as TIMER, Kaplan-Meier Plotter and TCGA databases, immunohistochemical method, and clinicopathological data of 92 LUADpatients between January 2008 and June 2016 were used to explore the EPOR expression, gene mutations affecting EPOR expression, EPOR-interacting or coexpressed genes, potential biological functions and the correlation of EPOR expression with prognosis, immune microenvironment and so on.All statistical analyses were performed in the R version 4.1.1.Results: In this study, the EPOR mRNA expression in LUAD tissues was possibly downregulated compared with that in normal lung tissues, but the EPOR protein expression in LUAD tissues was higher than that in paired normal lung tissues. Mutations in five genes, DDX60L, LGR6, POTEB3, RIF1 and SOX5, resulted in downregulation of EPOR expression, mutations in 10 genes includingC1orf168, DBX2 and EIF5B, resulted in upregulation of EPOR expression. Erichment analyses showed that EPOR is involved in neural tissue ligand-receptor interactions, MAPK and PI3K/Akt signaling pathways and cancer pathways. The KM Plotter and PrognoScan databases consistently concluded that EPOR was associated with prognosis in LUAD patients. Our clinicopathological data showed that high EPOR expression was associated with poorer OS (29.5 vs 46 months) and had a good predictive ability for 5-year survival probability. Conclusions: EPOR expression might be downregulated at the mRNA levels and significantly upregulated at the protein levels in LUAD, which showed that the mRNA and protein levels of EPOR are inconsistent.The high expression of EPOR was associated with poor prognosis and is expected to be a potential new prognostic marker for LUAD.

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Prognostic implications of programmed death ligand 1 expression in resected lung adenocarcinoma: a systematic review and meta-analysis

European Journal of Cardio-Thoracic Surgery ◽

10.1093/ejcts/ezaa172 ◽

2020 ◽

Vol 58 (5) ◽

pp. 888-898

Author(s):

Donglai Chen ◽

Yiming Mao ◽

Qifeng Ding ◽

Wei Wang ◽

Feng Zhu ◽

...

Keyword(s):

Gene Expression ◽

Protein Expression ◽

Lung Adenocarcinoma ◽

Messenger Rna ◽

Disease Free Survival ◽

Pooled Analysis ◽

The Cancer Genome Atlas ◽

Free Survival ◽

L1 Protein ◽

Disease Free

Abstract OBJECTIVES Conflicting results have been reported about the prognostic value of programmed death ligand 1 (PD-L1) protein and gene expression in lung adenocarcinoma. METHODS We performed a comprehensive online search to explore the association between PD-L1 expression (protein and messenger RNA) and overall survival (OS) or disease-free survival. Outcomes also included pooled rates of high PD-L1 protein expression in different cell types, per threshold used and per antibody used. A pooled gene expression analysis was also performed on 3 transcriptomic data sets that were obtained from The Cancer Genome Atlas database and the Gene Expression Omnibus database. RESULTS A total of 6488 patients from 25 studies were included. The pooled results suggested that high PD-L1 expression was associated with shorter OS [hazard ratio (HR) 1.57; P < 0.001] and disease-free survival (HR 1.341; P = 0.037) in the overall population. The overall pooled rate of high PD-L1 protein expression was 29% (95% confidence interval 23–34%) in tumour cells. In subgroup analysis, high PD-L1 protein expression in tumour cells predicted worse OS and disease-free survival. A pooled analysis of The Cancer Genome Atlas and Gene Expression Omnibus data sets revealed that higher levels of PD-L1 messenger RNA predicted poorer OS in the entire population. CONCLUSIONS This study is, to our knowledge, the largest pooled analysis on the subject to shed light on the high expression rate of PD-L1 and the prognostic value of high PD-L1 expression in resected lung adenocarcinomas. PD-L1 gene expression is a promising prognostic factor for patients with surgically resected lung adenocarcinoma. Standardization of staining should be underscored prior to routine implementation.

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LETM1 is a potential biomarker of prognosis in lung non-small cell carcinoma

BMC Cancer ◽

10.1186/s12885-019-6128-9 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Longzhen Piao ◽

Zhaoting Yang ◽

Ying Feng ◽

Chengye Zhang ◽

Chunai Cui ◽

...

Keyword(s):

Cox Regression ◽

Transmembrane Protein ◽

Small Cell Lung Carcinoma ◽

Clinical Stage ◽

Small Cell ◽

Cancer Prognosis ◽

Normal Lung ◽

Cell Lung Carcinoma ◽

Cox Regression Analysis ◽

Potential Biomarker

Abstract Background Although the leucine zipper-EF-hand-containing transmembrane protein 1 (LETM1) is one of the mitochondrial inner membrane proteins that is involved in cancer prognosis in various tumors, LETM1 as a biomarker for prognostic evaluation of non-small cell lung carcinoma (NSCLC) has not been well studied. Methods To address this issue, we used 75 cases NSCLC, 20 cases adjacent normal lung tissues and NSCLC cell lines. We performed immunohistochemistry staining and western blot analysis as well as immunofluorescence imaging. Results Our studies show that expression of LETM1 is significantly correlated with the lymph node metastasis (p = 0.003) and the clinical stage (p = 0.005) of NSCLC. The Kaplan-Meier survival analysis revealed that NSCLC patients with positive expression of LETM1 exhibits a shorter overall survival (OS) rate (p = 0.005). The univariate and multivariate Cox regression analysis indicated that LETM1 is a independent poor prognostic marker of NSCLC. In addition, the LETM1 expression is correlated with cancer stemness-related gene LGR5 (p < 0.001) and HIF1α expression (p < 0.001), but not with others. Moreover, LETM1 expression was associated with the expression of cyclin D1 (p = 0.003), p27 (p = 0.001), pPI3K(p85) (p = 0.025), and pAkt-Thr308 (p = 0.004). Further, our studies show in LETM1-positive NSCLC tissues the microvessel density was significantly higher than in the negative ones (p = 0.024). Conclusion These results indicate that LETM1 is a potential prognostic biomarker of NSCLC.

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The clinical and prognostic value of polo-like kinase 1 in lung squamous cell carcinoma patients: immunohistochemical analysis

Bioscience Reports ◽

10.1042/bsr20170852 ◽

2017 ◽

Vol 37 (4) ◽

Cited By ~ 8

Author(s):

Hefei Li ◽

Haibo Wang ◽

Zhenqing Sun ◽

Qiang Guo ◽

Hongyun Shi ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Lung Adenocarcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Prognostic Value ◽

Clinical Stage ◽

Lung Squamous Cell Carcinoma ◽

Immunohistochemical Analysis ◽

High Expression ◽

Normal Lung

Polo-like kinase 1 (PLK1) has been suggested to serve as an oncogene in most human cancers. The aim of our study is to present more evidence about the clinical and prognostic value of PLK1 in lung squamous cell carcinoma patients. The status of PLK1 was observed in lung adenocarcinoma, lung squamous cell carcinoma, and normal lung tissues through analyzing microarray dataset (GEO accession numbers: GSE1213 and GSE 3627). PLK1 mRNA and protein expressions were detected in lung squamous cell carcinoma and normal lung tissues by using quantitative real-time PCR (qRT-PCR) and immunohistochemistry. In our results, the levels of PLK1 in lung squamous cell carcinoma tissues were higher than that in lung adenocarcinoma tissues. Compared with paired adjacent normal lung tissues, the PLK1 expression was increased in lung squamous cell carcinoma tissues. Furthermore, high expression of PLK1 protein was correlated with differentiated degree, clinical stage, tumor size, lymph node metastasis, and distant metastasis. The univariate and multivariate analyses showed PLK1 protein high expression was an unfavorable prognostic biomarker for lung squamous cell carcinoma patients. In conclusion, high expression of PLK1 is associated with the aggressive progression and poor prognosis in lung squamous cell carcinoma patients.

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