LncRNA FOXP4-AS1 Promotes Progression of Ewing Sarcoma and Is Associated With Immune Infiltrates

Ewing sarcoma (ES) is a highly malignant primary bone tumor with poor prognosis. Studies have shown that abnormal expression of lncRNA influences the prognosis of tumor patients. Herein, we established that FOXP4-AS1 was up-regulated in ES and this correlated with poor prognosis. Further analysis illustrated that FOXP4-AS1 down-regulation repression growth, migration, along with invasion of ES. On the contrary, up-regulation of FOXP4-AS1 promoted the growth, migration, as well as invasion of ES. To explore the mechanism of FOXP4-AS1, Spearman correlation analysis was carried out to determine genes that were remarkably linked to FOXP4-AS1 expression. The potential functions and pathways involving FOXP4-AS1 were identified by GO analysis, Hallmark gene set enrichment analysis, GSEA, and GSVA. The subcellular fractionation results illustrated that FOXP4-AS1 was primarily located in the cytoplasm of ES cells. Then a ceRNA network of FOXP4-AS1 was constructed. Analysis of the ceRNA network and GSEA yielded two candidate mRNAs for FOXP4-AS1. Results of the combined survival analysis led us to speculate that FOXP4-AS1 may affect the expression of TMPO by sponging miR-298, thereby regulating the malignant phenotype of ES. Finally, we found that FOXP4-AS1 may modulates the tumor immune microenvironment in an extracellular vesicle-mediated manner. In summary, FOXP4-AS1 correlates with poor prognosis of ES. It promotes the growth, migration, as well as invasion of ES cells and may modulate the tumor immune microenvironment.

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Comprehensive Analysis of a ceRNA Network Identifies lncR-C3orf35 Associated with Poor Prognosis in Osteosarcoma

BioMed Research International ◽

10.1155/2020/3178037 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Yi Shi ◽

Jianhua Ren ◽

Ze Zhuang ◽

Wenhui Zhang ◽

Zhe Wang ◽

...

Keyword(s):

Poor Prognosis ◽

Immune Cell ◽

Bone Cancer ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Regulatory Mechanisms ◽

Messenger Rnas ◽

Cerna Network ◽

Potential Biomarker ◽

Hmgb1 Expression

Osteosarcoma is a highly malignant bone cancer which primarily occurs in children and young adults. Increasing evidence indicates that long noncoding RNAs (lncRNAs), which function as competing endogenous RNAs (ceRNAs) that sponge microRNAs (miRNAs) and messenger RNAs (mRNAs), play a pivotal role in the pathogenesis and progression of cancers. The regulatory mechanisms of lncRNA-mediated ceRNAs in osteosarcoma have not been fully elucidated. In this study, we identified differentially expressed lncRNAs, miRNAs, and mRNAs in osteosarcoma based on RNA microarray profiles in the Gene Expression Omnibus (GEO) database. A ceRNA network was constructed utilizing bioinformatic tools. Kaplan-Meier survival analysis showed that lncR-C3orf35 and HMGB1 were associated with poor prognosis of osteosarcoma patients. Furthermore, results of Gene Set Enrichment Analysis (GSEA) suggested that lncR-C3orf35 may be involved in cellular invasion, the Toll-like receptor signaling pathway, and immune cell infiltration in the tumor microenvironment. Further analysis showed that patients with osteosarcoma metastasis expressed higher levels of lncR-C3orf35 and HMGB1 compared to metastasis-free patients. Moreover, the metastasis-free survival rate of the high lncR-C3orf35/HMGB1 expression group was significantly lower than that of the low expression group. The ESTIMATE algorithm was used to calculate the immune score and stromal scores for each sample. High lncR-C3orf35 and HMGB1 levels were correlated with low immune scores. ImmuCellAI analysis revealed that a low proportion of macrophage infiltration was associated with high lncR-C3orf35 and HMGB1 expression. The differential expression of lncR-C3orf35, miR-142-3p, and HMGB1 was further verified by quantitative real-time PCR. This study indicates that lncR-C3orf35 could be considered as a novel potential biomarker and therapeutic target of osteosarcoma, which may contribute to a better understanding of ceRNA regulatory mechanisms.

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NRAS Expression is Associated With Prognosis and Tumor Immune Microenvironment in Lung Adenocarcinoma

10.21203/rs.3.rs-862652/v1 ◽

2021 ◽

Author(s):

Yueren Yan ◽

Zhendong Gao ◽

Han Han ◽

Yue Zhao ◽

Yang Zhang ◽

...

Keyword(s):

T Cells ◽

Lung Adenocarcinoma ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Expression Level ◽

Immune Microenvironment ◽

Kaplan Meier ◽

Tumor Immune Microenvironment ◽

Cox Analysis

Abstract Purpose: NRAS plays a pivotal role in progression of various kinds of somatic malignancies; however, the correlation between NRAS and lung adenocarcinoma is less known. We aim to analyze the prognostic value of NRAS expression in lung adenocarcinoma, and explore the relationship between NRAS and tumor immune microenvironment. Methods: We obtained the transcriptome pofiles and clinical data of LUAD from The Cancer Genome Atlas database and three Genome Expression Omnibus datasets. Specimens from 325 patients with completely resected lung adenocarcinoma were collected for immunohistochemical assays of NRAS, PD-L1, PD-1 and TIM-3. Then we performed gene set enrichment analysis to investigate cancer-related and immune-related signaling pathways. TIMER algorithms were performed to evaluate tumor immune infiltrating cells and immune-related biomarkers.Results: Compared with adjacent non-tumor tissue, NRAS expression was significantly upregulated in LUAD tissue. NRAS expression was significantly correlated with more advanced stage and positive lymph nodes. Kaplan-Meier curves and Cox analysis suggested that high NRAS expression led to a poor prognosis, and could be an independent prognostic factor in LUAD patients. Besides, NRAS expression was positively correlated with CD8+ T cells, macrophages, and neutrophils, and negatively correlated with B cells and CD4+ T cells. The expression level of NRAS was positively correlated with PD-L1, PD-1, and TIM-3 both at RNA and protein level. Conclusions: To conclude, we found NRAS a novel prognostic biomarker in LUAD. Besides, the expression level of NRAS may influence the prognosis of LUAD via various kinds of cancer-related pathways and remodeling TIM.

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P02.07 Characterization of the tumor immune microenvironment of pediatric posterior fossa A ependymomas

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-itoc8.19 ◽

2021 ◽

Vol 9 (Suppl 1) ◽

pp. A10.1-A10

Author(s):

J Lammers ◽

F Calkoen ◽

M Kranendonk ◽

A Federico ◽

M Kool ◽

...

Keyword(s):

Rna Sequencing ◽

Posterior Fossa ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Rna Expression ◽

Sequencing Data ◽

Immune Microenvironment ◽

Gene Set Enrichment ◽

Tumor Immune Microenvironment ◽

Immune Related Genes

BackgroundEpendymoma is the third most common brain tumor in children. At the moment, surgery and radiotherapy are the only effective treatments that can be offered, and despite this, a significant part of the patients relapse with no therapeutic salvage options. Therefore, new treatment modalities are needed. To develop immunotherapies for these children, knowledge of the tumor microenvironment is crucial. The current study aims to unravel the tumor immune microenvironment (TIME) of pediatric posterior fossa A (PFA) ependymomas.Materials and MethodsWe used bulk RNA sequencing data of 22 pediatric ependymomas. We defined two groups, hereafter called PFA immune+ (PFAI+) and PFAI-, based on the RNA expression levels of the NanoString panel of Human PanCancer Immune Profiling genes. We performed gene set enrichment analysis and deconvoluted the bulk RNA samples with ependymoma-specific single-cell RNA sequencing datasets. To validate our findings on a protein level, we applied immunohistochemistry with antibodies recognizing tumor-infiltrating lymphocytes, tumor-associated macrophages and microglia.ResultsUnsupervised hierarchical clustering of RNA expression of immune-related genes revealed two distinct PFA groups. Differential gene expression analysis showed that PFAI+ have a significantly higher expression of genes associated with immune functions, such as CD3E, CCR2, GZMA, CXCL9 and TRBC2. Accordingly, gene set enrichment analysis demonstrated that several immune pathways, including T-cell signalling, interferon-gamma response and TNFα signalling are enriched in PFAI+ ependymomas. RNA expression of immune checkpoints was also higher in PFAI+ tumors, indicating that these tumors might be more responsive to combinational therapies including immune checkpoint inhibitors. While immunohistochemistry showed low amounts of infiltrating CD3+, CD8+ and CD20+ cells, high numbers of CD163+ and HLA-DRA+ cells were detected. These cells were mainly located in regions of tumor necrosis. Increased amounts of CD4+ and CD8+ lymphocytes were present in PFAI+ tumors compared to PFAI- tumors. Deconvolution of the bulk RNA samples based on single-cell RNA sequencing data revealed an enrichment of myeloid cell populations, especially microglia and macrophages. Furthermore, PFAI+ tumors were found to contain significantly higher relative proportions of T-cells compared to PFAI- tumors (median of 3.76% for PFAI+ compared to 0.03% for PFAI-).ConclusionsWe suggest that pediatric posterior fossa A ependymomas can be divided into two groups based on the expression of immune-related genes, in which PFAI+ ependymomas are characterized by higher RNA expression levels of these genes and greater amounts of tumor-infiltrating immune cells. Several techniques showed an enrichment of T-lymphocytes in the PFAI+ ependymomas relative to the PFAI- ependymomas.Disclosure InformationJ. Lammers: None. F. Calkoen: None. M. Kranendonk: None. A. Federico: None. M. Kool: None. L. Kester: None. J. van der Lugt: None.

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Overexpressed XRCC2 as an independent risk factor for poor prognosis in glioma patients

Molecular Medicine ◽

10.1186/s10020-021-00316-0 ◽

2021 ◽

Vol 27 (1) ◽

Author(s):

Zhendong Liu ◽

Wang Zhang ◽

Xingbo Cheng ◽

Hongbo Wang ◽

Lu Bian ◽

...

Keyword(s):

Risk Factor ◽

Expression Pattern ◽

Poor Prognosis ◽

Independent Risk Factor ◽

Cox Regression ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Cellular Mechanisms ◽

Molecular Features ◽

Meta Analyses

Abstract Background XRCC2, a homologous recombination-related gene, has been reported to be associated with a variety of cancers. However, its role in glioma has not been reported. This study aimed to find out the role of XRCC2 in glioma and reveal in which glioma-specific biological processes is XRCC2 involved based on thousands of glioma samples, thereby, providing a new perspective in the treatment and prognostic evaluation of glioma. Methods The expression characteristics of XRCC2 in thousands of glioma samples from CGGA and TCGA databases were comprehensively analyzed. Wilcox or Kruskal test was used to analyze the expression pattern of XRCC2 in gliomas with different clinical and molecular features. The effect of XRCC2 on the prognosis of glioma patients was explored by Kaplan–Meier and Cox regression. Gene set enrichment analysis (GSEA) revealed the possible cellular mechanisms involved in XRCC2 in glioma. Connectivity map (CMap) was used to screen small molecule drugs targeting XRCC2 and the expression levels of XRCC2 were verified in glioma cells and tissues by RT-qPCR and immunohistochemical staining. Results We found the overexpression of XRCC2 in glioma. Moreover, the overexpressed XRCC2 was associated with a variety of clinical features related to prognosis. Cox and meta-analyses showed that XRCC2 is an independent risk factor for the poor prognosis of glioma. Furthermore, the results of GSEA indicated that overexpressed XRCC2 could promote malignant progression through involved signaling pathways, such as in the cell cycle. Finally, doxazosin, quinostatin, canavanine, and chrysin were identified to exert anti-glioma effects by targeting XRCC2. Conclusions This study analyzed the expression pattern of XRCC2 in gliomas and its relationship with prognosis using multiple datasets. This is the first study to show that XRCC2, a novel oncogene, is significantly overexpressed in glioma and can lead to poor prognosis in glioma patients. XRCC2 could serve as a new biomarker for glioma diagnosis, treatment, and prognosis evaluation, thus bringing new insight into the management of glioma.

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RNA N6-Methyladenosine Regulators Contribute to Tumor Immune Microenvironment and Have Clinical Prognostic Impact in Breast Cancer

Frontiers in Genetics ◽

10.3389/fgene.2021.650499 ◽

2022 ◽

Vol 12 ◽

Author(s):

Lan-Xin Mu ◽

You-Cheng Shao ◽

Lei Wei ◽

Fang-Fang Chen ◽

Jing-Wei Zhang

Keyword(s):

Breast Cancer ◽

Immune Cell ◽

Risk Model ◽

Cox Regression ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Prognostic Impact ◽

Immune Microenvironment ◽

Model Based ◽

Tumor Immune Microenvironment

Purpose: This study aims to reveal the relationship between RNA N6-methyladenosine (m6A) regulators and tumor immune microenvironment (TME) in breast cancer, and to establish a risk model for predicting the occurrence and development of tumors.Patients and methods: In the present study, we respectively downloaded the transcriptome dataset of breast cancer from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database to analyze the mutation characteristics of m6A regulators and their expression profile in different clinicopathological groups. Then we used the weighted correlation network analysis (WGCNA), the least absolute shrinkage and selection operator (LASSO), and cox regression to construct a risk prediction model based on m6A-associated hub genes. In addition, Immune infiltration analysis and gene set enrichment analysis (GSEA) was used to evaluate the immune cell context and the enriched gene sets among the subgroups.Results: Compared with adjacent normal tissue, differentially expressed 24 m6A regulators were identified in breast cancer. According to the expression features of m6A regulators above, we established two subgroups of breast cancer, which were also surprisingly distinguished by the feature of the immune microenvironment. The Model based on modification patterns of m6A regulators could predict the patient’s T stage and evaluate their prognosis. Besides, the low m6aRiskscore group presents an immune-activated phenotype as well as a lower tumor mutation load, and its 5-years survival rate was 90.5%, while that of the high m6ariskscore group was only 74.1%. Finally, the cohort confirmed that age (p < 0.001) and m6aRiskscore (p < 0.001) are both risk factors for breast cancer in the multivariate regression.Conclusion: The m6A regulators play an important role in the regulation of breast tumor immune microenvironment and is helpful to provide guidance for clinical immunotherapy.

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High RPS27A Expression Predicts Poor Prognosis in Patients With HPV Type 16 Cervical Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.752974 ◽

2021 ◽

Vol 11 ◽

Author(s):

Qiming Wang ◽

Yan Cai ◽

Xuewen Fu ◽

Liang Chen

Keyword(s):

Cervical Cancer ◽

Poor Prognosis ◽

Biological Significance ◽

Enrichment Analysis ◽

Hpv Infection ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Protein Protein Interaction ◽

Cervical Cancer Cells ◽

Cancer Genome Atlas

In recent years, the incidence and the mortality rate of cervical cancer have been gradually increasing, becoming one of the major causes of cancer-related death in women. In particular, patients with advanced and recurrent cervical cancers present a very poor prognosis. In addition, the vast majority of cervical cancer cases are caused by human papillomavirus (HPV) infection, of which HPV16 infection is the main cause and squamous cell carcinoma is the main presenting type. In this study, we performed screening of differentially expressed genes (DEGs) based on The Cancer Genome Atlas (TCGA) database and GSE6791, constructed a protein–protein interaction (PPI) network to screen 34 hub genes, filtered to the remaining 10 genes using the CytoHubba plug-in, and used survival analysis to determine that RPS27A was most associated with the prognosis of cervical cancer patients and has prognostic and predictive value for cervical cancer. The most significant biological functions and pathways of RPS27A enrichment were subsequently investigated with gene set enrichment analysis (GSEA), and integration of TCGA and GTEx database analyses revealed that RPS27A was significantly expressed in most cancer types. In this study, our analysis revealed that RPS27A can be used as a prognostic biomarker for HPV16 cervical cancer and has biological significance for the growth of cervical cancer cells.

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Alteration in the immune microenvironment based on APC status in MSS/pMMR colon cancer data retrieved from TCGA

10.21203/rs.3.rs-56379/v1 ◽

2020 ◽

Author(s):

Haishan Lin ◽

Hongchao Zhen ◽

Kun Shan ◽

Xiaoting Ma ◽

Bangwei Cao

Keyword(s):

Colon Cancer ◽

Cancer Patients ◽

Enrichment Analysis ◽

Tumor Immunotherapy ◽

Immune Checkpoints ◽

Immune Microenvironment ◽

Cancer Data ◽

T Cell Infiltration ◽

Colon Cancers ◽

Tumor Immune Microenvironment

Abstract Immunotherapy is currently the most advanced anti-tumor treatment approach. The efficacy of anti-tumor immunotherapy is closely related to the tumor immune microenvironment, including immune cells, infiltration of immune factors, and expression of immune checkpoints. At present, the biomarkers for predicting the efficacy of colon cancer immunotherapy do not cover all colon cancer patients suitable for immunotherapy. In this study, TCGA database was used to identify tumor genotypes suitable for anti-tumor immunotherapy. We found that some of the MSS/pMMR populations, that were initially considered unsuitable for immunotherapy, might actually be suitable. In APC-wt/MSS colon cancer, the expression of PD-1, PD-L1, CTLA4 and CYT（GZMA and PRF1）were increased. Based on calculations done by ESTIMATE and CIBERSORT algorithms, the ImmunoScore and the proportion of CT8+ T cell infiltration is increased in these patients. Enrichment analysis was done to screen signaling pathways involved in immune response, extracellular matrix, and cell adhesion. Tumors from 42 colon cancer patients, including 22 APC-mt/MSS and 20 APC-wt/MSS, were immunohistochemically evaluated for expression of CD8 and PD-L1. And APC-wt/MSS tumors showed significantly higher expression of CD8 and PD-L1 than APC-mt/MSS tumor. Based on the results, we found that some colon cancers of APC-wt/MSS are classified by Tumor Immune Microenvironment types (TIMTs) TMIT I. So that we speculate that APC-wt/MSS colon cancer patients could benefit from anti-tumor immunotherapy.

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LINC01018 and SMIM25 sponged miR-182-5p in endometriosis revealed by the ceRNA network construction

International Journal of Immunopathology and Pharmacology ◽

10.1177/2058738420976309 ◽

2020 ◽

Vol 34 ◽

pp. 205873842097630

Author(s):

Li Jiang ◽

Mengmeng Zhang ◽

Sixue Wang ◽

Yuzhen Xiao ◽

Jingni Wu ◽

...

Keyword(s):

Messenger Rna ◽

Kegg Pathway ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

Protein Protein Interaction ◽

Cerna Network ◽

Non Coding Rna ◽

Differentially Expressed Mirnas ◽

Long Non Coding Rna

The current study intended to explore the interaction of the long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) under the background of competitive endogenous RNA (ceRNA) network in endometriosis (EMs). The differentially expressed miRNAs (DEmiRs), differentially expressed lncRNA (DELs), and differentially expressed genes (DEGs) between EMs ectopic (EC) and eutopic (EU) endometrium based on three RNA-sequencing datasets (GSE105765, GSE121406, and GSE105764) were identified, which were used for the construction of ceRNA network. Then, DEGs in the ceRNA network were performed with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) analysis. Besides, the DEmiRs in the ceRNA network were validated in GSE124010. And the target DELs and DEGs of verified DEmiRs were validated in GSE86534. The correlation of verified DEmiRs, DEGs, and DELs was explored. Moreover, gene set enrichment analysis (GSEA) was applied to investigate the function of verified DEmiRs, DEGs, and DELs. Overall, 1352 DEGs and 595 DELs from GSE105764, along with 27 overlapped DEmiRs between GSE105765 and GSE121406, were obtained. Subsequently, a ceRNA network, including 11 upregulated and 16 downregulated DEmiRs, 7 upregulated and 13 downregulated DELs, 48 upregulated and 46 downregulated DEGs, was constructed. The GO and KEGG pathway analysis showed that this ceRNA network probably was associated with inflammation-related pathways. Furthermore, hsa-miR-182-5p and its target DELs (LINC01018 and SMIM25) and DEGs (BNC2, CHL1, HMCN1, PRDM16) were successfully verified in the validation analysis. Besides, hsa-miR-182-5p was significantly negatively correlated with these target DELs and DEGs. The GSEA analysis implied that high expression of LINC01018, SMIM25, and CHL1, and low expression of hsa-miR-182-5p would activate inflammation-related pathways in endometriosis EU samples. LINC01018 and SMIM25 might sponge hsa-miR-182-5p to upregulate downstream genes such as CHL1 to promote the development of endometriosis.

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Premature Activation of Immune Transcription Programs in Autoimmune-Predisposed Mouse Embryonic Stem Cells and Blastocysts

International Journal of Molecular Sciences ◽

10.3390/ijms21165743 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5743

Author(s):

Oktay Kirak ◽

Eugene Ke ◽

Kevin Y. Yang ◽

Anna Schwarz ◽

Lars Plate ◽

...

Keyword(s):

Histone Modifications ◽

Genetic Predisposition ◽

Autoimmune Diabetes ◽

Es Cells ◽

Embryonic Stem ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

Immune Functions ◽

Active Expression

Autoimmune diabetes is a complex multifactorial disease with genetic and environmental factors playing pivotal roles. While many genes associated with the risk of diabetes have been identified to date, the mechanisms by which external triggers contribute to the genetic predisposition remain unclear. Here, we derived embryonic stem (ES) cell lines from diabetes-prone non-obese diabetic (NOD) and healthy C57BL/6 (B6) mice. While overall pluripotency markers were indistinguishable between newly derived NOD and B6 ES cells, we discovered several differentially expressed genes that normally are not expressed in ES cells. Several genes that reside in previously identified insulin-dependent diabetics (Idd) genomic regions were up-regulated in NOD ES cells. Gene set enrichment analysis showed that different groups of genes associated with immune functions are differentially expressed in NOD. Transcriptomic analysis of NOD blastocysts validated several differentially overexpressed Idd genes compared to B6. Genome-wide mapping of active histone modifications using ChIP-Seq supports active expression as the promoters and enhancers of activated genes are also marked by active histone modifications. We have also found that NOD ES cells secrete more inflammatory cytokines. Our data suggest that the known genetic predisposition of NOD to autoimmune diabetes leads to epigenetic instability of several Idd regions.

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Infiltration of Immunoinflammatory Cells and Related Chemokine/Interleukin Expression in Different Gastric Immune Microenvironments

Journal of Immunology Research ◽

10.1155/2020/2450569 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Ang Wang ◽

Siru Nie ◽

Zhi Lv ◽

Jing Wen ◽

Yuan Yuan

Keyword(s):

Gastric Cancer ◽

Gastric Mucosa ◽

Immune Cell ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Upward Trend ◽

Immune Microenvironment ◽

Gene Set Enrichment ◽

Expression Characteristic ◽

Precancerous Stage

Gastric mucosal immune microenvironment plays an important role in the occurrence and development of diseases such as inflammation and cancer. In the present study, single-sample gene set enrichment analysis (ssGSEA) was used to evaluate the expression of cytokines and the degree of immune cell infiltration in four different gastric mucosa tissues from normal gastric mucosa, simple gastritis, and atrophic gastritis to gastric cancer. Here, we show the immune microenvironments of these four gastric mucosae were significantly different. From inflammation to gastric cancer, most immunoinflammatory cells showed a downward trend such as central memory CD4 T cell. Instead, several cells showed an upward trend such as macrophage. Additionally, we found some chemokines/interleukins were illustrated to be low expressed (or highly expressed) in precancerous stage and highly expressed (or low expressed) in postcancerous stage, which demonstrated an opposite expression characteristic in pre-/postcancerous stage.

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