The Prognostic Value of ADAMTS8 and Its Role as a Tumor Suppressor in Breast Cancer

Qia, Zhang; Kanyomse, Quist; Luo, Chenghao; Mo, Qingfan; Zhao, Xunping; Wang, Long; Peng, Weiyan; Ren, Guosheng

doi:10.1080/07357907.2022.2128367

Cited by 3 publications

(3 citation statements)

References 42 publications

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“…For ADAMTS8, it appears that some cancers have decreased ADAMTS8 expression 45 , 46 . Meanwhile, ADAMTS8 exhibited an inhibitory influence on tumor proliferation and invasion 47 - 49 . The above arguments were well demonstrated in breast cancer in our study.…”

Section: Discussionmentioning

confidence: 99%

Novel Implication of the Basement Membrane for Breast Cancer Outcome and Immune Infiltration

Tian¹,

Luo²,

Tang³

et al. 2023

Int. J. Biol. Sci.

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Therapeutic failure in breast cancer patients is largely attributed to postoperative advancement and therapy resistance. Nevertheless, an efficacious prognostic signature for recognizing this population is lacking. The basement membrane (BM) has been proven to be strongly involved in cancer progression and metastasis, and has the potential to be a powerful predictor in breast cancer. In this study, substantial bulk RNA transcriptomics, single cell RNA transcriptomics and clinical information were collected from TCGA-BRCA, METABRIC and GSE96058, and Kaplan-Meier survival curves, single cell analysis and in vitro experiments were conducted to validate the signature. From the results, a prognostic index, namely, the BMscore, was established with six pivotal BM genes, specifically LOXL1, FBLN1, FBLN5, SDC1, ADAMTS8 and PXDNL. Verification by independent cohorts showed that breast cancer patients with high BMscore had a distinctly worse outcome. By integrating the BMscore and clinical factors, we constructed a prognostic nomogram that displayed good predictive capability. Furthermore, we evaluated the implication of the BMscore in breast cancer immune infiltration. More importantly, a strongly positive correlation between the BMscore and EMT activity was revealed with immunohistochemistry and in vitro experiments. Taken together, we provided a novel BMscore gene signature for breast cancer patients to predict clinical prognosis and metastasis accurately, which may help with individualized clinical decision-making.

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Section: Discussionmentioning

confidence: 99%

Novel Implication of the Basement Membrane for Breast Cancer Outcome and Immune Infiltration

Tian¹,

Luo²,

Tang³

et al. 2023

Int. J. Biol. Sci.

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show abstract

“…[29] The ADAMTS genes participate in a wide range of biological processes such as extracellular matrix assembly and degradation, and ADAMTS8 has been proven to function as a tumor suppressor gene for BRCA. [30] DCAF12L2 is involved in a variety of cellular processes such as cell cycle progression and apoptosis, and it was only found to correlate with the microsatellite instability in colorectal cancer [31] but no research was reported about BRCA. PCDHA10 has been demonstrated an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters, and decreased DNA methylation in PCDHA10 has just been found as a risk factor for early-onset high myopia in young children.…”

Section: Discussionmentioning

confidence: 99%

Establishment of a 6-signature risk model associated with cellular senescence for predicting the prognosis of breast cancer

Zhang,

Yu,

Zhu

et al. 2023

Medicine

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This study focused on screening novel markers associated with cellular senescence for predicting the prognosis of breast cancer. The RNA-seq expression profile of BRCA and clinical data were obtained from TCGA. The pam algorithm was used to cluster patients based on senescence-related genes. The weighted gene co-expression network analysis was used to identify co-expressed genes, and LASSO-Cox analysis was performed to build a risk prognosis model. The performance of the model was also evaluated. We additionally explored the role of senescence in cancer development and possible regulatory mechanism. The patients were clustered into 2 subtypes. A total of 5259 genes significantly related to senescence were identified by weighted gene co-expression network analysis. LASSO-Cox finally established a 6-signature risk model (ADAMTS8, DCAF12L2, PCDHA10, PGK1, SLC16A2, and TMEM233) that exhibited favorable and stable performance in our training, validation, and whole BRCA datasets. Furthermore, the superiority of our model was also observed after comparing it to other published models. The 6-signature was proved to be an independent risk factor for prognosis. In addition, mechanism prediction implied the activation of glycometabolism processes such as glycolysis and TCA cycle under the condition of senescence. Glycometabolism pathways were further found to negatively correlate with the infiltration level of CD8 T-cells and natural killer cells but positively correlate with M2 macrophage infiltration and expressions of tissue degeneration biomarkers, which suggested the deficit immune surveillance and risk of tumor migration. The constructed 6-gene model based on cellular senescence could be an effective indicator for predicting the prognosis of BRCA.

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“…ADAMTS8 serves as a suppressor or oncogene in numerous cancers (Zhong and Khalil, 2019). In breast cancer, its overexpression may be associated with longer OS and progression-free survival, which may take part in cell cycle regulation, and may be related to the EGFR/Akt signaling pathway (Zhang et al, 2022a). Based on some findings, it was lower in NSCLC tissues compared with normal tissues (Dunn et al, 2004).…”

Section: Figurementioning

confidence: 99%

Function and prognostic value of basement membrane -related genes in lung adenocarcinoma

Zhang

Liu

et al. 2023

Front. Pharmacol.

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Background: Lung adenocarcinoma (LUAD) has become a common cause of cancer-related death. Many studies have shown that the basement membrane (BM) is associated with the development of cancer. However, BM-related gene expression and its relationship to LUAD prognosis remains unclear.Methods: BM-related genes from previous studies were used. Clinical and mRNA expression information were obtained from TCGA database. Cox, minimum absolute contraction, and selection operator regression were applied to analyze the selected genes affecting LUAD prognosis. A prognostic-risk model was then established. Furthermore, this study applied Kaplan-Meier analysis to assess the outcomes of high- and low-risk groups, then explored their differences in drug sensitivity. The DSigDB database was used to screen for therapeutic small-molecule drugs.Results: Fourteen prognostic models based on BM-related genes were successfully constructed and validated in patients with LUAD. We also found that independence was a prognostic factor in all 14 BM-based models. Functional analysis showed that the enrichment of BM-related genes mainly originated from signaling pathways related to cancer. The BM-based model also suggested that immune cell infiltration is associated with checkpoints. The low-risk patients may benefit from cyclopamine and docetaxel treatments.Conclusion: This study identified a reliable biomarker to predict survival in patients with LUAD and offered new insights into the function of BM-related genes in LUAD.

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The Prognostic Value of ADAMTS8 and Its Role as a Tumor Suppressor in Breast Cancer

Cited by 3 publications

References 42 publications

Novel Implication of the Basement Membrane for Breast Cancer Outcome and Immune Infiltration

Novel Implication of the Basement Membrane for Breast Cancer Outcome and Immune Infiltration

Establishment of a 6-signature risk model associated with cellular senescence for predicting the prognosis of breast cancer

Function and prognostic value of basement membrane -related genes in lung adenocarcinoma

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