Erythropoietin Receptor is a Risk Factor for Prognosis: A Potential Biomarker in Lung Adenocarcinoma

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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MicroRNA-96 inhibits FoxO3a function in IPF fibroblasts on type I collagen matrix

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00127.2014 ◽

2014 ◽

Vol 307 (8) ◽

pp. L632-L642 ◽

Cited By ~ 37

Author(s):

Richard Seonghun Nho ◽

Jintaek Im ◽

Yen-Yi Ho ◽

Polla Hergert

Keyword(s):

Type I Collagen ◽

Collagen Matrix ◽

Lung Fibroblasts ◽

Normal Lung ◽

Type I ◽

Mrna Levels ◽

Protein Levels ◽

Dose Dependent Fashion ◽

Mrna And Protein Expression

Idiopathic pulmonary fibrosis (IPF) is a lethal and progressive lung disease characterized by persistent (myo)fibroblasts and the relentless accumulation of collagen matrix. Unlike normal lung fibroblasts, IPF lung fibroblasts have suppressed forkhead box O3a (FoxO3a) activity, which allows them to expand in this diseased environment. microRNA-96 (miR-96) has recently been found to directly bind to the 3′-untranslated region of FoxO3a mRNA, which subsequently inhibits its function. We examined whether aberrantly low FoxO3a expression is in part due to increased miR-96 levels in IPF fibroblasts on polymerized collagen, thereby causing IPF fibroblasts to maintain their pathological properties. miR-96 expression was upregulated in IPF fibroblasts compared with control fibroblasts when cultured on collagen. In contrast, FoxO3a mRNA levels were reduced in most IPF fibroblasts. However, when miR-96 function was inhibited, FoxO3a mRNA and protein expression were increased, suppressing IPF fibroblast proliferation and promoting their cell death in a dose-dependent fashion. Likewise, FoxO3a and its target proteins p21, p27, and Bim expression was also increased in the presence of a miR-96 inhibitor in IPF fibroblasts. However, when control fibroblasts were treated with miR-96 mimic, FoxO3a, p27, p21, and Bim mRNA and protein levels were decreased. In situ hybridization analysis further revealed the presence of enhanced miR-96 expression in cells within the fibroblastic foci of IPF lung tissue. Our results suggest that when IPF fibroblasts interact with collagen-rich matrix, pathologically altered miR-96 expression inhibits FoxO3a function, causing IPF fibroblasts to maintain their pathological phenotype, which may contribute to the progression of IPF.

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Interactive Verification Analysis of Multiple Sequencing Data for Identifying Potential Biomarker of Lung Adenocarcinoma

BioMed Research International ◽

10.1155/2020/8931419 ◽

2020 ◽

Vol 2020 ◽

pp. 1-18

Author(s):

Hongjun Fei ◽

Songchang Chen ◽

Chenming Xu

Keyword(s):

Lung Adenocarcinoma ◽

Differentially Expressed Genes ◽

Gene Expression Omnibus ◽

Differentially Expressed ◽

Normal Lung ◽

Pcr Analysis ◽

Sequencing Data ◽

Hub Genes ◽

Lung Cancers ◽

Potential Biomarker

Background. Lung adenocarcinoma (LUAD) comprises around 40% of all lung cancers, and in about 70% of patients, it has spread locally or systemically when first detected leading to a worse prognosis. Methods. We filtered out differentially expressed genes (DEGs) based on the RNA sequencing data in the Gene Expression Omnibus database and verified and deeply analyzed screened DEGs using a combined bioinformatics approach. Results. Expressions of 11,143 genes in 694 nontumor lung tissues and LUAD cases from 8 independent laboratories were analyzed; 188 mRNAs were identified as differentially expressed genes (DEGs). A PPI network constructed with 188 DEGs screened out 8 hub DEGs (CDH5, PECAM1, VWF, CLDN5, COL1A1, MMP9, SPP1, and IL6) which highly interconnected with other nodes. The expression levels of 8 hub genes in LUAD and control were assessed in the Oncomine database, and the results were consistent. The survival curves of 8 hub genes showed that their expressions are significantly related to the prognosis of lung cancer and LUAD patients except for IL6. Since the expression of IL6 is nonspecific and highly sensitive, we choose the other 7 hub genes we had verified to do the next analysis. Mutual exclusivity or cooccurrence analysis of 7 hub genes identified a tendency towards cooccurrence between CDH5, PECAM1, and VWF in LUAD. The coexpression profiles of CDH5 in LUAD were identified, and we found that PECAM1 and VWF coexpressed with CDH5. Immunohistochemistry and RT-PCR analysis showed that higher levels of CDH5, PECAM1, and VWF were expressed in normal lung tissues but a low or undetectable level was found in LUAD tissues. Conclusions. Taken together, we speculate that CDH5, PECAM1, and VWF played an important role in LUAD.

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Absence of HTATIP2 Expression in A549 Lung Adenocarcinoma Cells Promotes Tumor Plasticity in Response to Hypoxic Stress

Cancers ◽

10.3390/cancers12061538 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1538

Author(s):

Minghua Li ◽

Jing Li ◽

Xiaofang Guo ◽

Hua Pan ◽

Qingyu Zhou

Keyword(s):

Lung Adenocarcinoma ◽

Parental Control ◽

Adaptation To Hypoxia ◽

Mrna Levels ◽

Hypoxic Stress ◽

Sorafenib Treatment ◽

Mesenchymal Transition ◽

Protein Levels ◽

Metabolic Plasticity ◽

The Impact

HIV-1 Tat Interactive Protein 2 (HTATIP2) is a tumor suppressor, of which reduced or absent expression is associated with increased susceptibility to tumorigenesis and enhanced tumor invasion and metastasis. However, whether the absent expression of HTATIP2 is a tumor-promoting factor that acts through improving tumor adaptation to hypoxia is unclear. Here, we established a stable HTATIP2-knockdown A549 human lung adenocarcinoma cell line (A549shHTATIP2) using lentiviral-delivered HTATIP2-targeting short hairpin RNA (shRNA), employed a double subcutaneous xenograft model and incorporated photoacoustic imaging and metabolomics approaches to elucidate the impact of the absent HTATIP2 expression on tumor response to hypoxic stress. Results from the in vivo study showed that A549shHTATIP2 tumors exhibited accelerated growth but decreased intratumoral oxygenation and angiogenesis and reduced sensitivity to sorafenib treatment as compared with their parental counterparts. Moreover, results of the immunoblot and real-time PCR analyses revealed that the HIF2α protein and mRNA levels in vehicle-treated A549shHTATIP2 tumors were significantly increased (p < 0.01 compared with the parental control tumors). Despite the strong HIF2α-c-Myc protein interaction indicated by our co-immunoprecipitation data, the increase in the c-Myc protein and mRNA levels was not significant in the A549shHTATIP2 tumors. Nonetheless, MCL-1 and β-catenin protein levels in A549shHTATIP2 tumors were significantly increased (p < 0.05 compared with the parental control tumors), suggesting an enhanced β-catenin/c-Myc/MCL-1 pathway in the absence of HTATIP2 expression. The finding of significantly decreased E-cadherin (p < 0.01 compared with vehicle-treated A549shHTATIP2 tumors) and increased vimentin (p < 0.05 compared with sorafenib-treated A549 tumors) protein levels in A549shHTATIP2 tumors implicates that the absence of HTATIP2 expression increases the susceptibility of A549 tumors to sorafenib-activated epithelial-mesenchymal transition (EMT) process. Comparison of the metabolomic profiles between A549 and A549shHTATIP2 tumors demonstrated that the absence of HTATIP2 expression resulted in increased tumor metabolic plasticity that enabled tumor cells to exploit alternative metabolic pathways for survival and proliferation rather than relying on glutamine and fatty acids as a carbon source to replenish TCA cycle intermediates. Our data suggest a mechanism by which the absent HTATIP2 expression modulates tumor adaptation to hypoxia and promotes an aggressive tumor phenotype by enhancing the HIF2α-regulated β-catenin/c-Myc/MCL-1 signaling, increasing the susceptibility of tumors to sorafenib treatment-activated EMT process, and improving tumor metabolic plasticity.

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MiR-22-3p Expression is down-regulated in lung adenocarcinoma

Acta Biochimica Polonica ◽

10.18388/abp.2020_5540 ◽

2021 ◽

Author(s):

Dong-Jie Ma ◽

Xiao-Yun Zhou ◽

Ying-Zhi Qin ◽

Zhen-Huan Tian ◽

Hong-Sheng Liu ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

Lung Adenocarcinoma ◽

Time Correlation ◽

Clinicopathological Characteristics ◽

Immunohistochemical Method ◽

Maximum Diameter ◽

Normal Lung ◽

Control Group ◽

Matrix Metalloproteinase 3 ◽

Significant Difference

Background: Our current study was performed with an attempt to detect the expression of microRNA-22-3p (miR-22-3p) in lung adenocarcinoma, as well as to analyze its role in clinical practice. In addition, its relationship with vascular endothelial growth factor (VEGF) and metastasis related indexes was focused. Material and Method: The trials in which 62 cases of lung adenocarcinoma were received to collect tumor tissue (study group) and normal lung tissue (control group) were eligible for this study. The expression of miR-22-3p in the two groups was detected through RT-PCR. Immunohistochemical method was used to detect the expression of VEGF and leukocyte differentiation antigen 31 (CD31) marked microvessel density (MVD) in lung adenocarcinoma. The expressions of matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-7 (MMP-7) in lung adenocarcinoma were also detected through the use of Western Blot. Results: The present study revealed significant difference in the expression of miR-22-3p between the two groups. No significant difference in the expression of gender, age, neural invasion and the number of lesions were observed between groups. There was significant difference in the expression of miR-22-3p in the maximum diameter of tumor, pleural recidivism, vascular recidivism, lymph node metastasis and different TNM stages. Based on survival analysis, miR-22-3p was linked to survival time. Correlation analysis indicated that there was negative correlation between miR-22-3p and VEGF, miR-22-3p and MVD, miR-22-3p and MMP-3, and miR-22-3p and MMP-7 in lung adenocarcinoma. Conclusion: Our findings provide evidence that miR-22-3p is low expressed in lung adenocarcinoma tissues and the low expression of miR-22-3p is closely associated with clinicopathological characteristics and the prognosis. MiR-22-3p may be involved in the tumor progression of lung adenocarcinoma and may serve as a biomarker for the diagnosis and prognosis of lung adenocarcinoma.

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Blood Levels of NLRP3 Inflammasome Components is Associated with Obsessive Compulsive Disorder

10.1101/2020.01.30.20019646 ◽

2020 ◽

Author(s):

Melike Tetik ◽

Nese Direk ◽

Betul Onder ◽

Cansu Aykac ◽

Burcu Ekinci ◽

...

Keyword(s):

Inflammatory Response ◽

Obsessive Compulsive Disorder ◽

Nlrp3 Inflammasome ◽

Mrna Levels ◽

Hamilton Depression Scale ◽

Obsessive Compulsive ◽

Compulsive Disorder ◽

Protein Levels ◽

Caspase 1 ◽

Potential Biomarker

ABSTRACTBackgroundInflammation has a well-known role in the pathogenesis of a range of neuropsychiatric disorders such as major depressive disorder and schizophrenia. Previous studies provided evidence regarding its possible involvement in the etiology of obsessive-compulsive disorder (OCD). However, mechanisms explaining the association of inflammation with OCD are lacking. The NLRP3 inflammasome complex initiates and mediates inflammatory response, which explain one of the most important key mechanisms behind inflammatory response. In this study, we aimed to determine a possible association between NLRP3 inflammasome and OCD, and to evaluate its relationship with clinical features.MethodsThis case-control study included 103 participants (51 OCD and 52 healthy controls). OCD patients were diagnosed using DSM-IV criteria. All participants were evaluated by psychiatric inventories, i.e. Yale Brown Obsessive Compulsive Scale, Hamilton Depression Scale, and Hewitt Multidimensional Perfectionism Scale. Peripheral blood mononuclear cells (PBMCs) were isolated from fresh blood samples. RNA and protein were extracted from PBMCs and expression of NLRP3 inflammasome components were evaluated by quantitative real-time PCR (qPCR) and Western blotting. Serum IL-1beta and IL-18 cytokine levels were determined by ELISA.ResultsNEK7 and CASP1 mRNA levels were significantly higher in OCD patients, compared to controls. Pro-Caspase-1 protein levels were elevated, as well. Regression analysis showed that NEK7 mRNA and Caspase-1 protein levels can differentiate OCD and healthy control groups.Discussionpro-Caspase-1 mRNA and protein levels in PBMCs, as well as NEK7 mRNA levels are potential biomarker candidates in OCD. Our results may prompt research into possible role of NLRP3 inflammasome in OCD etiology.

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Translocator Protein (TSPO) as a Potential Biomarker in Human Cancers

International Journal of Molecular Sciences ◽

10.3390/ijms19082176 ◽

2018 ◽

Vol 19 (8) ◽

pp. 2176 ◽

Cited By ~ 11

Author(s):

Nimisha Bhoola ◽

Zukile Mbita ◽

Rodney Hull ◽

Zodwa Dlamini

Keyword(s):

Lung Cancer ◽

Cell Line ◽

Cancer Cell ◽

Normal Lung ◽

Mrna Levels ◽

Rt Pcr ◽

Fluorescent Intensity ◽

Potential Biomarker ◽

Cancer Tissues

TSPO is a receptor involved in the regulation of cellular proliferation, apoptosis and mitochondrial functions. Previous studies showed that the expression of TSPO protein correlated positively with tumour malignancy and negatively with patient survival. The aim of this study was to determine the transcription of Tspo mRNA in various types of normal and cancer tissues. In situ hybridization was performed to localise the Tspo mRNA in various human normal and cancer tissues. The relative level of Tspo mRNA was quantified using fluorescent intensity and visual estimation of colorimetric staining. RT-PCR was used to confirm these mRNA levels in normal lung, lung cancer, liver cancer, and cervical cancer cell lines. There was a significant increase in the level of transcription in liver, prostate, kidney, and brain cancers while a significant decrease was observed in cancers of the colon and lung. Quantitative RT-PCR confirmed that the mRNA levels of Tspo are higher in a normal lung cell line than in a lung cancer cell line. An increase in the expression levels of Tspo mRNA is not necessarily a good diagnostic biomarker in most cancers with changes not being large enough to be significantly different when detected by in situ hybridisation.

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ZNF768 Expression Associates with High Proliferative Clinicopathological Features in Lung Adenocarcinoma

Cancers ◽

10.3390/cancers13164136 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4136

Author(s):

Audrey Poirier ◽

Andréanne Gagné ◽

Philippe Laflamme ◽

Meagan Marcoux ◽

Michèle Orain ◽

...

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Cell Lines ◽

Cancer Cell ◽

Zinc Finger Protein ◽

Cancer Cell Lines ◽

Clinicopathological Features ◽

Normal Lung ◽

Growth Factor Signaling ◽

Protein Levels

Lung adenocarcinoma (LUAD) is the most common type of lung cancer and a leading cause of cancer-related deaths worldwide. Despite important recent advances, the prognosis for LUAD patients is still unfavourable, with a 5 year-survival rate close to 15%. Improving the characterization of lung tumors is important to develop alternative options for the diagnosis and the treatment of this disease. Zinc-finger protein 768 (ZNF768) is a transcription factor that was recently shown to promote proliferation and repress senescence downstream of growth factor signaling. Although ZNF768 protein levels were found to be elevated in LUAD compared to normal lung tissue, it is currently unknown whether ZNF768 expression associates with clinicopathological features in LUAD. Here, using tissue microarrays of clinical LUAD surgical specimens collected from 364 patients, we observed that high levels of ZNF768 is a common characteristic of LUAD. We show that ZNF768 protein levels correlate with high proliferative features in LUAD, including the mitotic score and Ki-67 expression. Supporting a role for ZNF768 in promoting proliferation, we report that ZNF768 depletion severely impairs proliferation in several lung cancer cell lines in vitro. A marked decrease in the expression of key proliferative genes was observed in cancer cell lines depleted from ZNF768. Altogether, our findings support a role for ZNF768 in promoting proliferation of LUAD.

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Intratumor heterogeneity of stage IA lung adenocarcinoma by multiregion whole exome sequencing and association with survival.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.8545 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 8545-8545 ◽

Cited By ~ 1

Author(s):

Kelly Quek ◽

Jun Li ◽

Junya Fujimoto ◽

Jianhua Zhang ◽

Jinliang Wang ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Gene Mutations ◽

Normal Lung ◽

Intratumor Heterogeneity ◽

Cancer Gene ◽

Whole Exome ◽

Potential Biomarker ◽

Stage Ia ◽

Early Carcinogenesis

8545 Background: Our previous study has suggested that complex genomic intratumor heterogeneity (gITH) was associated with an increased risk of relapse in patients with localized lung adenocarcinomas (LUAD). We have launched a study to investigate molecular and immune profile ITH of Stage IA NSCLC (a patient population with no optimal biomarker to guide postsurgical therapy) to understand the molecular evolution during early carcinogenesis and to identify biomarkers for early detection and intervention. Here, we report the preliminary analysis on gITH. Methods: We performed multiregion whole exome sequencing on 30 Stage IA LUAD and matched normal lung tissue to a median sequencing depth of 494x. 15 patients have relapsed within 3 years post-surgery (cases) and 15 patients have not relapsed with a minimum of 5-year postsurgical follow up (controls). Cases and controls are 1:1 matched for the key prognostic factors including tumor size, smoking status, age, gender, ethnicity and lobectomy or wedge resection. Shannon diversity index (SDI) was used to quantify ITH in each individual tumor. Kaplan-Meier method was used to evaluate the relationship between ITH and disease-free survival (DFS) as well as overall survival (OS). Results: Consistent with our previous study, 108 of 110 (98.2%) canonical cancer gene mutations were shared events by all regions of individual tumor. Compared to non-relapsed controls, tumors from relapsed cases demonstrated significantly higher degree of ITH (SDI of 1.78 in cases vs 1.58 for controls, p = 0.016). Higher degree of gITH was associated with shorter DFS (p = 0.008) and shorter OS (p = 0.0153). Significantly higher mutation burden was observed in tumors from relapsed patients (median of 10.86 mutations per MB in cases vs 7.45 mutations per MB in controls, p = 0.03). Analysis of gITH on a larger cohort and on predicted neoantigen, methylation, gene expression and immune profiles are in progress. Conclusions: Majority of cancer gene mutations are clonal events during early carcinogenesis of LUAD. Complex gITH may be associated with more aggressive biology and inferior clinical outcome in patients with Stage IA LUAD, therefore, may be evaluated as a potential biomarker.

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Study on the Mechanism of Cancer/Testicular Antigen FSIP1 in Regulating Autophagy and Promoting Survival of Lung Cancer Cells

Journal of Clinical Medicine Research ◽

10.32629/jcmr.v2i1.322 ◽

2021 ◽

Vol 2 (1) ◽

Author(s):

Xiaoping Zhu ◽

Yingping Song ◽

Wei Wang ◽

Weiqi Yang

Keyword(s):

Gene Expression ◽

Quantitative Analysis ◽

Lung Adenocarcinoma ◽

Actinomycin D ◽

Normal Lung ◽

Time Points ◽

Protein Levels ◽

Adenocarcinoma Cells ◽

Significant Difference ◽

Lung Adenocarcinoma Cells

Objective — To investigate the molecular mechanism of FSIP1 gene expression and autophagy inhibition in patients with lung adenocarcinoma. Methods — TTP expression in lung adenocarcinoma H1299, H1975 and normal lung forming cells was detected by QRT-PCR and Western Bloting. Quantitative analysis and Western Bloting were performed by transfecting pCMV-FSIPI at 24h, 48h and 72h respectively to analyze the expression of autophagy related factors like P62, LC3II/LCI and BecIinl. The transient transfection of overexpressed and empty plasmid was performed by adding 10 mg/ml of actinomycin D. After the termination of this transcription, RNA extraction was performed at different time points to detect the expression of Beclin1m RNA at different time points. After adding TNF-a by transfection plasmid, lung adenocarcinoma cells were divided into different groups, including no-load group, FSIPI group, no-load + TNF-A group, and FSIPI + TNF-a group. The gene expression of P50, c-Rel and NF-KBp65 in the nucleus was analyzed by immunofluorescence and Western Bloting. Lung adenocarcinoma was divided into Ikba-mut no-load group, FSIPI no-load group, 1Ikba-mut group, FSIPI group and FSIPI+ Ikba-mut group. FSIPI expression and autophagy gene expression were detected by quantitative analysis and Western Bloting. Results — In lung adenocarcinoma cells, FSIP1 RNA and protein levels were RELATIVELY low, and autophagy Becline and LC 3II/I had lower RNA and protein levels after overexpression of FSIPI compared with the no-load group. Transcription is terminated by the addition of actinomycin D. There was no significant difference in the expression of the autophagy-related gene BEC LINEM between FSIP1 and the no-load group. After overexpression of FSIPI, according to Western Bloting results, nuclear C-Rel and P65 proteins were less than those in the no-load +TNF-a group and the no-load group, whileP50 protein did not change significantly. Combined with immunofluorescence studies, it was found that the expressions of c-Rel and P65 were significantly decreased after FSIP1 overexpression compared with the no-load group, while the expression of P50 was not significantly changed. Conclusion — FSIP1 is usually low expressed in lung adenocarcinoma. Overexpression of FSIP1 can effectively inhibit the nuclear metastasis of C-Rel and NF-KBp65, thus inhibiting autophagy of the cells.

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

Diagnostics ◽

10.3390/diagnostics11071250 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1250

Author(s):

Seungyun Jee ◽

Hyunsung Kim ◽

Seongsik Bang ◽

Yeseul Kim ◽

Ha Young Park ◽

...

Keyword(s):

Tumor Suppressor ◽

Lung Adenocarcinoma ◽

Clinical Stage ◽

Disease Free Survival ◽

The Cancer Genome Atlas ◽

Proliferation Index ◽

Normal Lung ◽

Clinicopathological Parameters ◽

Low Level ◽

Potential Biomarker

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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