Increased expression of TET3 predicts unfavorable prognosis in patients with ovarian cancer-a bioinformatics integrative analysis

Cao, Tiefeng; Pan, Wenwei; Sun, Xiangrong; Shen, Huimin

doi:10.1186/s13048-019-0575-4

Cited by 56 publications

(34 citation statements)

References 42 publications

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“…Likewise, we have compared gene expressions among COAD, adjacent normal colon and healthy colon; or lung cancer, adjacent normal lung and healthy lung. 10 As previously reported, 10 , 20 data were normalized in R environment using NormalizeBetweenArrays.…”

Section: Methodsmentioning

confidence: 99%

Integrated Bioinformatic Analysis of SARS-CoV-2 Infection Related Genes ACE2, BSG and TMPRSS2 in Aerodigestive Cancers

He¹,

Hua²,

Sun³

et al. 2021

JIR

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Background Cancer patients are more vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than the general population, with lung epithelial cells or enterocytes being the main targets. However, the expressions of SARS-CoV-2 entry-related genes in aerodigestive cancers have not been fully elucidated. Methods In this study, the expressions of SARS-CoV-2 receptors and cofactors, including angiotensin I-converting enzyme 2 (ACE2), basigin (BSG) and transmembrane serine protease 2 (TMPRSS2), were comprehensively assessed. We compared BSG and TMPRSS2 expressions between aerodigestive cancers and matched normal tissues through Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Furthermore, expressions in healthy colon tissues at different anatomical locations were explored using the Genotype-Tissue Expression (GTEx) dataset. In addition, expressions among different tumor stages and the prognostic values were detected through GEPIA2. Moreover, the correlation between gene expression and immune infiltration was explored via Tumor Immune Estimation Resource (TIMER). Finally, expressions in primary colorectal cancer (CRC), lung metastasis and liver metastasis were investigated using the Gene Expression Omnibus (GEO) dataset GSE41258. Results Similar to ACE2, TMPRSS2 and BSG were also highly expressed in the digestive tracts. Intriguingly, BSG/TMPRSS2 expression in adjacent normal colon tissue or lung tissue was higher than that in corresponding healthy tissue, whereas they varied not among different tumor stages and correlated not with prognosis in aerodigestive cancers. Moreover, ACE2 was expressed at higher levels in lung metastases from CRC than in normal lung tissues. Conclusion SARS-CoV-2 entry genes were highly expressed in CRC, and we reported for the first time higher expression of ACE2 in lung metastases from CRC than in normal lung, indicating that these patients may be more susceptible to extrapulmonary or pulmonary SARS-CoV-2 infection. Since our study is a bioinformatic analysis, further experimental evidences and clinical data are urgently needed.

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Section: Methodsmentioning

confidence: 99%

Integrated Bioinformatic Analysis of SARS-CoV-2 Infection Related Genes ACE2, BSG and TMPRSS2 in Aerodigestive Cancers

He¹,

Hua²,

Sun³

et al. 2021

JIR

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“…It was used to compare ACE2 expression between cancer and normal tissues. In addition, we downloaded the data of number of fragments per kilobase of exon per million reads (FPKM) in cancer, adjacent normal tissue and healthy tissue from TCGA or GTEx, which were normalized in R environment using NormalizeBetweenArrays [24]. In addition, pairwise comparisons of ACE2 expression were performed in TCGA datasets.…”

Section: Comparisons Of Ace2 Expression Among Cancer Adjacent Normalmentioning

confidence: 99%

Bioinformatic Analysis of Correlation between Immune Infiltration and COVID-19 in Cancer Patients

Huang¹,

He²,

Hua³

et al. 2020

Int. J. Biol. Sci.

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In 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused infections worldwide. However, the correlation between the immune infiltration and coronavirus disease 2019 (COVID-19) susceptibility or severity in cancer patients remains to be fully elucidated. ACE2 expressions in normal tissues, cancers and cell lines were comprehensively assessed. Furthermore, we compared ACE2 expression between cancers and matched normal tissues through Gene Expression Profiling Interactive Analysis (GEPIA). In addition, we performed gene set enrichment analysis (GSEA) to investigate the related signaling pathways. Finally, the correlations between ACE2 expression and immune infiltration were investigated via Tumor Immune Estimation Resource (TIMER) and GEPIA. We found that ACE2 was predominantly expressed in both adult and fetal tissues from the digestive, urinary and male reproductive tracts; moreover, ACE2 expressions in corresponding cancers were generally higher than that in matched healthy tissues. GSEA showed that various metabolic and immune-related pathways were significantly associated with ACE2 expression across multiple cancer types. Intriguingly, we found that ACE2 expression correlated significantly with immune cell infiltration in both normal and cancer tissues, especially in the stomach and colon. These findings proposed a possible fecal-oral and maternal-fetal transmission of SARS-CoV-2 and suggested that cancers of the respiratory, digestive or urinary tracts would be more vulnerable to SARS-CoV-2 infection.

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“…Furthermore, increasing evidence suggests a close association between TET3 and PD‐L1 in cancers. Cao et al [ 24 ] demonstrated that the elevated expression of TET3 is associated with poor clinic‐pathological functions and poor prognosis for ovarian cancer. More importantly, the active demethylation of PD‐L1 promoter was concomitant with the upregulation of TET3 in human breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of NF‐κB is required for oleanolic acid to downregulate PD‐L1 by promoting DNA demethylation in gastric cancer cells

Yang

et al. 2020

J Biochem & Molecular Tox

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Gastric cancer is one of the most common causes of cancer‐related death worldwide. Immunotherapy via programmed cell death protein 1 (PD‐1)/programmed cell death‐ligand 1 (PD‐L1) blockade has shown benefits for gastric cancer. Epigenetic DNA methylation critically regulates cancer immune checkpoints. We investigated how the natural compound oleanolic acid (OA) affected PD‐L1 expression in gastric cancer cells. Interleukin‐1β (IL‐1β) at 20 ng/mL was used to stimulate human gastric cancer MKN‐45 cells. IL‐1β significantly increased PD‐L1 expression, which was abolished by OA. Next, OA‐treated MKN‐45 cells were co‐cultured with activated and PD‐1‐overexpressing Jurkat T cells. OA restored IL‐2 levels in the co‐culture system and increased T cell killing toward MKN‐45 cells. Overexpression of PD‐L1 eliminated OA‐enhanced T cell killing capacity; however, PD‐1 blocking antibody abrogated the cytotoxicity of T cells. Moreover, OA abolished IL‐1β‐increased DNA demethylase activity in MKN‐45 cells. DNA methyltransferase inhibitor 5‐azacytidine rescued OA‐reduced PD‐L1 expression; whereas DNA demethylation inhibitor gemcitabine inhibited PD‐L1 expression, and, in combination with OA, provided more potent inhibitory effects. Furthermore, OA selectively reduced the expression of DNA demethylase TET3 in IL‐1β‐treated MKN‐45 cells, and overexpression of TET3 restored OA‐reduced PD‐L1 expression. Finally, OA disrupted nuclear factor κB (NF‐κB) signaling IL‐1β‐treated MKN‐45 cells, and overexpression of NF‐κB restored OA downregulation of TET3 and PD‐L1. The cytotoxicity of T cells toward MKN‐45 cells was also weakened by NF‐κB overexpression. Altogether, OA blocked the IL‐1β/NF‐κB/TET3 axis in gastric cancer cells, leading to DNA hypomethylation and downregulation of PD‐L1. Our discoveries suggested OA as an epigenetic modulator for immunotherapy or an adjuvant therapy against gastric cancer.

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Increased expression of TET3 predicts unfavorable prognosis in patients with ovarian cancer-a bioinformatics integrative analysis

Cited by 56 publications

References 42 publications

Integrated Bioinformatic Analysis of SARS-CoV-2 Infection Related Genes ACE2, BSG and TMPRSS2 in Aerodigestive Cancers

Integrated Bioinformatic Analysis of SARS-CoV-2 Infection Related Genes ACE2, BSG and TMPRSS2 in Aerodigestive Cancers

Bioinformatic Analysis of Correlation between Immune Infiltration and COVID-19 in Cancer Patients

Inhibition of NF‐κB is required for oleanolic acid to downregulate PD‐L1 by promoting DNA demethylation in gastric cancer cells

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