STC1 is a Novel Biomarker Associated with Immune Characteristics and Prognosis of Bladder Cancer

Sun, Jiale; Wei, Xuedong; You, Jiawei; Yue, Wenchang; Ouyang, Jun; Ling, Zhixin; Hou, Jianquan

doi:10.2147/ijgm.s329723

Cited by 14 publications

(12 citation statements)

References 44 publications

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“…STC1 is also secreted by multiple cell types in the tumor microenvironment, including cancer cells, cancer associated fibroblasts, macrophages and adipocytes (48,(50)(51)(52). STC1 reversely correlates with checkpoint therapy efficacy in patients with melanoma and lung cancer and is associated with poor patient survival across multiple cancer types (49,(53)(54)(55)(56)(57)(58)(59)(60). Using RNAi technology and neutralizing antibodies, we discovered that ANGPTL4 and STC1 differentially regulated cancer-associated mesothelial cell tumor-promoting functions, and that neutralization of ANGPTL4 alone or in combination with STC1 prevented metastasis.…”

Section: Discussionmentioning

confidence: 99%

Cancer-associated mesothelial cell–derived ANGPTL4 and STC1 promote the early steps of ovarian cancer metastasis

Bajwa¹,

Kordylewicz²,

Bilecz³

et al. 2023

JCI Insight

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Ovarian cancer (OvCa) preferentially metastasizes in association with mesothelial cell-lined surfaces. We sought to determine if mesothelial cells are required for OvCa metastasis and detect alterations in mesothelial cell gene expression and cytokine secretion upon interaction with OvCa cells. Using omental samples from patients with high-grade serous OvCa and mouse models with Wt1-driven GFP-expressing mesothelial cells, we validated the intratumoral localization of mesothelial cells during human and mouse OvCa omental metastasis. Removing mesothelial cells ex vivo from human and mouse omenta or in vivo using diphtheria toxin mediated ablation in Msln-Cre mice, significantly inhibited OvCa cell adhesion and colonization. Human ascites induced angiopoietinlike 4 (ANGPTL4) and stanniocalcin 1 (STC1) expression and secretion by mesothelial cells. Inhibition of STC1 or ANGPTL4 via RNAi, obstructed OvCa cell-induced mesothelial cell to mesenchymal transition while inhibition of ANGPTL4 alone obstructed OvCa cell-induced mesothelial cell migration and glycolysis. Inhibition of mesothelial cell ANGPTL4 secretion via RNAi prevented mesothelial cell induced monocyte migration, endothelial cell vessel formation and OvCa cell adhesion, migration, and proliferation. In contrast, inhibition of mesothelial cell STC1 secretion via RNAi prevented mesothelial cell induced endothelial cell vessel formation and OvCa cell adhesion, migration, proliferation, and invasion. Additionally, blocking ANPTL4 function with antibodies reduced the ex vivo colonization of three different OvCa cell lines on human omental tissue explants and in vivo colonization of ID8 p53-/-Brca2-/cells on mouse omenta. These findings indicate that mesothelial cells are important to the initial stages of OvCa metastasis, and that the crosstalk between mesothelial cells and the tumor microenvironment, promotes OvCa metastasis through the secretion of ANGPTL4.

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Section: Discussionmentioning

confidence: 99%

Cancer-associated mesothelial cell–derived ANGPTL4 and STC1 promote the early steps of ovarian cancer metastasis

Bajwa¹,

Kordylewicz²,

Bilecz³

et al. 2023

JCI Insight

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“…Aberrant expression of STC1 had been observed in human carcinoma samples including colorectal cancer, breast cancer, lung adenocarcinoma, hepatocellular carcinoma, and thyroid carcinomas [ 35 – 37 ]. A recent study reveals that STC1 is a novel biomarker associated with immune characteristics and prognosis of bladder cancer [ 38 ] and also inhibits APC phagocytosis, contributes to tumor immune evasion and immunotherapy resistance [ 39 ]. In addition, STC1 can suppress the function of the macrophages [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analyses of Stromal-Immune Score-Related Competing Endogenous RNA Networks In Colon Adenocarcinoma

Tong

Peng

et al. 2022

Disease Markers

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Although recent clinical investigations emphasize the roles of myriad diversities of RNAs in stromal and immune components in the tumor microenvironment, especially in colon adenocarcinoma, however, analyses of “competing endogenous RNAs (ceRNA)” network in association with stromal and immune scores have yet to be determined. This study was conducted to explore the regulatory mechanisms of a stromal-immune score-based ceRNA network in colon adenocarcinoma. Stromal and immune scores of colon adenocarcinoma tumor samples were calculated by using the ESTIMATE algorithm. Differential expression analysis between samples with high/low stromal and immune scores was performed, followed by functional annotation for the overlapping DEmRNAs. The ceRNA network was constructed by differential expression analysis, prediction of RNA-RNA interaction, and correlation with clinicopathological parameters of the patients, which were further verified by external datasets and experiments. Colon adenocarcinoma patients having higher immune scores exhibited prolonged overall survival. RNA dataset analyses from TCGA revealed aberrant expressions of a total of 2052 mRNAs, 108 lncRNAs, and 70 miRNAs between high and low stromal/immune groups. Functional annotation mapped the differentially overexpressed mRNAs for immune-associated GO terms. To construct the ceRNA network, a total of 48 lncRNAs, 40 miRNAs, and 199 mRNAs were sorted out. A dysregulated ceRNA network consisting of 6 lncRNAs, 11 miRNAs, and 39 mRNAs was constructed by comparing RNA expressions between cancer as well as adjacent normal tissues. The ceRNA regulatory axis “MIAT/miR-532-3p/STC1” was regarded as a potential hit by the comprehensive analysis. The RT-qPCR assay showed upregulation of MIAT and STC1 while downregulation of hsa-miR-532-3p expression in cancer. Thus, our study highlights the potential role of a stromal-immune score-based ceRNA network in the colon adenocarcinoma microenvironment. The ceRNA axis MIAT/miR-532-3p/STC1 could serve as a promising therapeutic target for colon adenocarcinoma.

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“…26 A study illustrated that STC1 is highly expressed in bladder cancer, enhances PD-L1 expression, and increases the degree of T cell immune infiltration. 27 The role of these feature genes in tumor progression has been elucidated, but their prognostic value has not been fully explored. The prognostic genes Collectively, the 9-feature genes screened based on the ITGB superfamily in our study were not only related to LUAD prognosis but also used as a potential target for LUAD treatment.…”

Section: Discussionmentioning

confidence: 99%

“…KRT81, a hair keratin, has become a biomarker of breast cancer and was revealed to promote cancer cell migration and invasion 26 . A study illustrated that STC1 is highly expressed in bladder cancer, enhances PD‐L1 expression, and increases the degree of T cell immune infiltration 27 …”

Section: Discussionmentioning

confidence: 99%

Construction of a prognostic risk assessment model for lung adenocarcinoma based on Integrin β family‐related genes

Wang

et al. 2022

Clinical Laboratory Analysis

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Background Integrin β (ITGB) superfamily plays an essential role in the intercellular connection and signal transmission. It was exhibited that overexpressing of ITGB family members promotes the malignant progression of lung adenocarcinoma (LUAD), but the relationship between ITGB superfamily and the LUAD prognosis remains unclear. Methods In this study, the samples were assigned to different subgroups utilizing non‐negative matrix factorization clustering according to the expression of ITGB family members in LUAD. Kaplan–Meier (K‐M) survival analysis revealed the significant differences in the prognosis between different ITGB subgroups. Subsequently, we screened differentially expressed genes among different subgroups and conducted univariate Cox analysis, random forest feature selection, and multivariate Cox analysis. 9‐feature genes (FAM83A, AKAP12, PKP2, CYP17A1, GJB3, TMPRSS11F, KRT81, MARCH4, and STC1) in the ITGB superfamily were selected to establish a prognostic assessment model for LAUD. Results In accordance with the median risk score, LUAD samples were divided into high‐ and low‐risk groups. The receiver operating characteristic (ROC) curve of LUAD patients’ survival was predicted via K‐M survival curve and principal component analysis dimensionality reduction. This model was found to have a favorable performance in LUAD prognostic assessment. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of differentially expressed genes between groups and Gene Set Enrichment Analysis (GSEA) of intergroup samples confirmed that the high‐ and low‐risk groups had evident differences mainly in the function of extracellular matrix (ECM) interaction. Risk score and univariate and multivariate Cox regression analyses of clinical factors showed that the prognostic model could be applied as an independent prognostic factor for LUAD. Then, we draw the nomogram of 1‐, 3‐, and 5‐year survival of LUAD patients predicted with the risk score and clinical factors. Calibration curve and clinical decision curve proved the favorable predictive ability of nomogram. Conclusion We constructed a LUAD prognostic risk model based on the ITGB superfamily, which can provide guidance for clinicians on their prognostic judgment.

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STC1 is a Novel Biomarker Associated with Immune Characteristics and Prognosis of Bladder Cancer

Cited by 14 publications

References 44 publications

Cancer-associated mesothelial cell–derived ANGPTL4 and STC1 promote the early steps of ovarian cancer metastasis

Cancer-associated mesothelial cell–derived ANGPTL4 and STC1 promote the early steps of ovarian cancer metastasis

Comprehensive Analyses of Stromal-Immune Score-Related Competing Endogenous RNA Networks In Colon Adenocarcinoma

Construction of a prognostic risk assessment model for lung adenocarcinoma based on Integrin β family‐related genes

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