EFNA3 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in patients with lung adenocarcinoma

Deng, Mingming; Tong, Run; Zhang, Zhe; Liang, Caihong; Zhou, Xiaoming; Hou, Gang

doi:10.1186/s12935-021-02226-x

Cited by 12 publications

(12 citation statements)

References 47 publications

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“…EFNA3 is a hypoxia regulated gene and is a GPI-anchored ligand for the EPH receptors involved in cell adhesion and motility. It is a negative prognostic factor of gastric, ovarian, and lung cancers [ 38 , 39 , 40 ]. DDX10 is an RNA helicase that is frequently lost in ovarian cancer [ 41 ] and is a poor prognostic factor in osteosarcoma [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of a Tumor Cell Associated Type I IFN Resistance Gene Expression Signature of Human Melanoma, the Components of Which Have a Predictive Potential for Immunotherapy

Ladányi

Rásó

Barbai

et al. 2022

IJMS

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We developed a human melanoma model using the HT168-M1 cell line to induce IFN-α2 resistance in vitro (HT168-M1res), which was proven to be maintained in vivo in SCID mice. Comparing the mRNA profile of in vitro cultured HT168-M1res cells to its sensitive counterpart, we found 79 differentially expressed genes (DEGs). We found that only a 13-gene core of the DEGs was stable in vitro and only a 4-gene core was stable in vivo. Using an in silico cohort of IFN-treated melanoma tissues, we validated a differentially expressed 9-gene core of the DEGs. Furthermore, using an in silico cohort of immune checkpoint inhibitor (ICI)-treated melanoma tissues, we tested the predictive power of the DEGs for the response rate. Analysis of the top four upregulated and top four downregulated genes of the DEGs identified WFDC1, EFNA3, DDX10, and PTBP1 as predictive genes, and analysis of the “stable” genes of DEGs for predictive potential of ICI response revealed another 13 genes, out of which CDCA4, SOX4, DEK, and HSPA1B were identified as IFN-regulated genes. Interestingly, the IFN treatment associated genes and the ICI-therapy predictive genes overlapped by three genes: WFDC1, BCAN, and MT2A, suggesting a connection between the two biological processes.

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Section: Discussionmentioning

confidence: 99%

Identification of a Tumor Cell Associated Type I IFN Resistance Gene Expression Signature of Human Melanoma, the Components of Which Have a Predictive Potential for Immunotherapy

Ladányi

Rásó

Barbai

et al. 2022

IJMS

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“…EphrinA3 (EFNA3) can play a pivotal role in tumorigenesis. For instance, EFNA3 can affect lung adenocarcinoma clinical prognosis and immune checkpoint therapy efficacy [ 29 ]. MiR-210 has been found to target EFNA3 to accelerate the peripheral nerve sheath tumor cell proliferation and invasion [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

LncRNA LINC01270 aggravates the progression of gastric cancer through modulation of miR-326/EFNA3 axis

et al. 2022

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Gastric cancer (GC) is lethal malignancy, which is associated with high mortality. Long noncoding RNA LINC01270 has been identified to act as a potential oncogene in several cancers. However, its role and related regulatory mechanism in GC are yet to be illustrated. The levels of lncRNA LINC01270, miR-326, and EphrinA3 (EFNA3) were assessed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8) and colony formation assays were applied for analyzing cell proliferation. Transwell assay was used for measuring cellular migration and invasion. Western blot analysis was employed for evaluating the protein levels. Luciferase reporter and RNA pull-down assays were utilized to verify the binding ability between LINC01270 (or EFNA3) and miR-326. Our findings indicated that LINC01270 expression was significantly up-regulated in GC tissues and cell lines. Additionally, LINC01270 knockdown attenuated GC progression through inhibiting cell proliferation, migration, and invasion. Functional experiments identified that lncRNA LINC01270 could positively regulate EFNA3 expression by serving as a competing endogenous RNA (ceRNA) for miR-326. Through rescue assays, inhibition of GC progression caused by LINC01270 suppression was found to be reversed by the application of miR-326 inhibitor or EFNA3 overexpression. Overall, our work demonstrated that lncRNA LINC01270 can accelerate cell proliferation, migration, and invasion via modulating miR-326/EFNA3 axis. These findings might implicate the potential role of lncRNA LINC01270 in GC treatment.

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“…EFNA3 is located in the 1q21.3 region of the human chromosome ( 23 ). The epidermal differentiation complex gene cluster is located in this region.…”

Section: Discussionmentioning

confidence: 99%

The 1q21.3 region driver gene EFNA3 promotes disease progression via inhibition of lung adenocarcinoma cell apoptosis

Dong¹,

Wu²,

Guo³

et al. 2022

Transl Cancer Res TCR

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Background Lung adenocarcinoma (LUAD) is the leading cause of cancer deaths in the world. Therefore, it is necessary to explore the underlying mechanism of EFNA3 (a 1q21.3 region driver gene) in the progression of LUAD cells. Methods Differentially-expressed genes (DEGs) in LUAD tissues were screened based on The Cancer Genome Atlas (TCGA) database. The gene copy number variations in the 1q21.3 region were clarified by copy number variation analysis. Genes associated with overall survival (OS) were identified by Kaplan-Meier (KM) analysis. The intersection of the genes was used to obtain the driver genes. LUAD patients were grouped with driver gene expression, and the DEGs were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to identify the enrichment pathways of the driver genes. EFNA3 was knocked down using lentiviral infection in A549 and PC9 cell lines. The efficiencies of lentiviral infection were confirmed by RT-PCR (reverse transcription polymerase chain reaction). After EFNA3 knockdown, changes in cell viability were confirmed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, changes in cell proliferation and apoptosis were confirmed by enzyme-linked immunosorbent assay (ELISA), while changes in the expression of apoptosis-related proteins ( Bax and caspase 3 ) were confirmed by RT-PCR and western blot. Results A total of 483 LUAD samples and 59 normal control samples were obtained from TCGA database, and 640 upregulated genes were identified. 154 genes with a coefficient of copy number variations greater than 10% in the 1q23.1 region and 1,247 genes that were significantly associated with patient OS were selected. The intersection results indicated that EFNA3 might be a driver gene of LUAD. KEGG enrichment analysis indicated that the DEGs were mainly enriched in apoptosis-related pathways. Cell experiments showed that after lentiviral knockdown of EFNA3 , EFNA3 messenger RNA (mRNA) and protein expression was significantly reduced (P<0.05), cell viability was markedly reduced (P<0.05), LUAD cell apoptosis increased notably (P<0.05), and LUAD cell proliferation decreased significantly (P<0.05). After EFNA3 knockdown, the expression of apoptosis-related proteins ( Bax and caspase3 ) and mRNA in LUAD cells increased markedly (P<0.05). Conclusions As a driver gene in the progression of LUAD, EFNA3 mainly affects the progression of LUAD by regulating LUAD cell apoptosis.

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EFNA3 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in patients with lung adenocarcinoma

Cited by 12 publications

References 47 publications

Identification of a Tumor Cell Associated Type I IFN Resistance Gene Expression Signature of Human Melanoma, the Components of Which Have a Predictive Potential for Immunotherapy

Identification of a Tumor Cell Associated Type I IFN Resistance Gene Expression Signature of Human Melanoma, the Components of Which Have a Predictive Potential for Immunotherapy

LncRNA LINC01270 aggravates the progression of gastric cancer through modulation of miR-326/EFNA3 axis

The 1q21.3 region driver gene EFNA3 promotes disease progression via inhibition of lung adenocarcinoma cell apoptosis

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