INHBA upregulation correlates with poorer prognosis in patients with esophageal squamous cell carcinoma

Lyu, Shanshan; Jiang, Chao; Xu, Rui; Huang, Yuhua; Yan, Shumei

doi:10.2147/cmar.s160186

Cited by 36 publications

(26 citation statements)

References 22 publications

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“…By further analyzing our previously published gene expression microarray data from these cell lines (14, 29), we found that both IL13R α 2 and INHBA exhibit increased expression levels in metastatic compared to non-metastatic breast cancer cells and that overexpression of both genes can similarly predict worse DMFS of patients with grade 3 tumors. This is consistent with previous reports suggesting that INHBA overexpression or increased Activin A plasma levels are associated with poor prognosis in lung, gastric, pancreatic and esophageal cancers (37–40). Our data presented here also demonstrate that shRNA-mediated depletion of INHBA in metastatic breast cancer cells led to suppression of IL13Rα2 mRNA and protein levels, whereas treatment of non-metastatic cells with Activin A resulted in upregulation of IL13Rα2 expression.…”

Section: Discussionsupporting

confidence: 93%

Activin A Signaling Regulates IL13Rα2 Expression to Promote Breast Cancer Metastasis

et al. 2019

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Metastatic dissemination of cancer cells to distal organs is the major cause of death for patients suffering from the aggressive basal-like breast cancer (BLBC) subtype. Recently, we have shown that interleukin 13 receptor alpha 2 (IL13Rα2) is a critical gene that is overexpressed in a subset of BLBC primary tumors associated with poor distant metastasis-free survival (DMFS) and can promote extravasation and metastasis of breast cancer cells to the lungs. However, the upstream signaling mechanisms that promote aberrant IL13Rα2 expression during tumor progression remain unknown. Driven by our previously published gene expression microarray data derived from a well-characterized cell line model for BLBC progression, we show that both Inhibin βA (INHBA) and IL13Rα2 genes exhibit similarly higher expression levels in metastatic compared to non-metastatic cells and that overexpression of both genes predicts worse metastasis-free survival of patients with high grade tumors. Activin A, a member of the TGFβ superfamily comprising two INHBA subunits, has been shown to play context-depended roles in cancer progression. Here, we demonstrate that INHBA depletion downregulates IL13Rα2 expression in metastatic breast cancer cells, whereas treatment with Activin A in non-metastatic cells increases its expression levels. We also find that Activin A predominantly induces Smad2 phosphorylation and to a lesser extent activates Smad3 and Akt. Interestingly, we also show that Activin A-mediated upregulation of IL13Rα2 is Smad2-dependent since knocking down Smad2 or using the ALK4/ALK5 inhibitors EW-7197 and SB-505124 abolishes this effect. Most importantly, our data indicate that knocking down INHBA levels in breast cancer cells delays primary tumor growth, suppresses migration in vitro and inhibits the formation of lung metastases in vivo. Conclusively, our findings presented here suggest that the development of therapeutic interventions employing small molecule inhibitors against Activin receptors or neutralizing antibodies targeting Activin A ligand, could serve as alternative approaches against breast tumors overexpressing INHBA and/or IL13Rα2.

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Section: Discussionsupporting

confidence: 93%

Activin A Signaling Regulates IL13Rα2 Expression to Promote Breast Cancer Metastasis

et al. 2019

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“…There are also reports in the literature that the effect of suppressing the development of colon cancer can be achieved by immunosuppression of CXCL3 [23][24][25][26][27]. INHBA has a significant relationship with the occurrence and development of gastric, esophageal, and ovarian cancers, and studies have reported that the immunosuppressive treatment of INHBA can reduce the rate of deterioration of gastric and ovarian cancers [28][29][30]. STC1 can promote the metastasis of colon cancer [31,32].…”

Section: Discussionmentioning

confidence: 99%

Prediction and identification of immune genes related to the prognosis of patients with colon adenocarcinoma and its mechanisms

Chen

Cao

et al. 2020

World J Surg Onc

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Background: Colon adenocarcinoma (COAD) is a gastrointestinal tumor with a high degree of malignancy. Its deterioration process is closely related to the tumor microenvironment, and transcription factors (TF) play a regulatory role in this process. Currently, there is a lack of exploration between the genes related to the COAD tumor microenvironment and the survival prognosis of patients. Models composed of multiple genes usually predict the survival prognosis of patients more accurately than single genes. We can analyze the multigene models that can predict the prognosis of COAD from the current database. Methods: The limma package of the R programming language is used for gene differential expression analysis. Kaplan-Meier curve is used to analyze the relationship between the patient risk score model and survival data. The hazard model is used to analyze the relationship between the risk score and the clinical data of COAD patients. The information of immune genes and immune cells is obtained from IMMPORT database and TIMER database. Receiver operating characteristic (ROC) curve is used to judge the stability of the model. Results: We found 7 immune genes, which can built a risk score model to predict the survival prognosis of COAD. According to univariate and multivariate analysis, the risk score can be used as an independent predictor. The content of some immune microenvironment cells will also increase as the risk score increases. Conclusions: We found 7 immune genes, such as SLC10A2 (solute carrier family 10 member 2), CXCL3 (C-X-C motif chemokine ligand 3), IGHV5-51 (immunoglobulin heavy variable 5-51), INHBA (inhibin subunit beta A), STC1 (stanniocalcin 1), UCN (urocortin), and OXTR (oxytocin receptor), can constitute a model for predicting the prognosis of COAD. They may provide potential therapeutic targets for clinical treatment of COAD.

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“…There are also reports in the literature that the effect of suppressing the development of colon cancer can be achieved by immunosuppression of CXCL3 [12][13][14][15][16]. INHBA has a significant relationship with the occurrence and development of gastric, esophageal, and ovarian cancers, and studies have reported that the immunosuppressive treatment of INHBA can reduce the rate of deterioration of gastric and ovarian cancers [17][18][19]. STC1OXTR, and UCN can promote the metastasis of colon cancer [20][21][22][23].…”

Section: Discussionmentioning

confidence: 99%

Prediction and identification of immune genes related to the prognosis of patients with colon adenocarcinoma and its mechanisms

Chen

et al. 2020

Preprint

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Abstract Background Colon adenocarcinoma(COAD) is a type of gastrointestinal tumor with a high degree of malignancy, and its immunotherapy method has been stagnant. Recently, with the development of network databases and the development of bioinformatics tools, we can analyze the data in the current database to find out which genes may be the target of immunotherapy for COAD. Methods We use various codes and packages in R language to analyze the downloaded data, construct a riskScore model of immune genes and clinical data, and use Cox regression analysis to explore the clinical relationship between riskScore and COAD. Results We found that seven immune genes associated with the survival prognosis of COAD were related to the construction of a riskScore model. And Cox regression analysis found that there was clinical significance and statistical significance between the riskScore model and clinical data of COAD. Some traditional immune microenvironment cells also increase their cell content with the increase of riskScore. Conclusions We found 7 immune genes (SLC10A2, CXCL3, IGHV5-51, INHBA, STC1, UCN, and OXTR) that affect the clinical prognosis of COAD patients and can construct a riskScore model. It may be a target for future COAD immunotherapy.

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INHBA upregulation correlates with poorer prognosis in patients with esophageal squamous cell carcinoma

Cited by 36 publications

References 22 publications

Activin A Signaling Regulates IL13Rα2 Expression to Promote Breast Cancer Metastasis

Activin A Signaling Regulates IL13Rα2 Expression to Promote Breast Cancer Metastasis

Prediction and identification of immune genes related to the prognosis of patients with colon adenocarcinoma and its mechanisms

Prediction and identification of immune genes related to the prognosis of patients with colon adenocarcinoma and its mechanisms

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