Tensin2 Is a Novel Diagnostic Marker in GIST, Associated with Gastric Location and Non-Metastatic Tumors

Salmikangas, Sami; Böhling, Tom; Merikoski, Nanna; Jagdeo, Joanna; Sampo, Mika; Vesterinen, Tiina; Sihto, Harri

doi:10.3390/cancers14133212

Cited by 4 publications

(2 citation statements)

References 42 publications

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“…It was noted the metastatic cases demonstrated lower expression of TNS2 compared to nonmetastatic samples; however, fewer metastatic cases were involved in the study (17/148 patients) (Table .2). 61…”

Section: Tensinmentioning

confidence: 99%

The molecular and clinical role of Tensin 1/2/3 in cancer

Mainsiouw

Ryan

Hafizi

et al. 2023

J Cellular Molecular Medi

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Local and systemic processes defining cancer are summarized in the classic and modified 'hallmarks of cancer', providing a conceptual tool to visualize a multi-pathway system (Figure 1). 1 Over the previous two decades, a mechanistic link between the family of structural proteins known as Tensins and primary malignancies has been proposed. [2][3][4][5] The initial hypotheses on the four members of the Tensin family focussed on their role as either structural support or focal adhesion adaptor proteins, providing a critical link between the extracellular matrix (ECM) and intracellular cytoskeleton. 6,7 However, this was likely an oversimplification with more recent evidence suggesting additional signal transduction roles. Furthermore, the dysregulation of focal adhesion complexes is one recognized mechanism behind the ability of cancer cells to metastasise. A clear role or mechanism of action in oncogenesis for Tensins has not been elucidated, and findings appear tumour type-specific. 2 The growing body of evidence for a diagnostic, prognostic and potential therapeutic role for these proteins mandates a clearer understanding of their molecular biology and oncogenic function. Tensin 4 (CTEN) has received the most focus in the literature and was recently reviewed in Liao et al (2021). 8 The remaining three Tensin family members share

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Section: Tensinmentioning

confidence: 99%

The molecular and clinical role of Tensin 1/2/3 in cancer

Mainsiouw

Ryan

Hafizi

et al. 2023

J Cellular Molecular Medi

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“…In addition, a previously collected series of 543 STS samples were investigated by using IHC and tissue microarray (TMA) from the following subtypes: fibrosarcoma, GIST, LPS, leiomyosarcoma, malignant peripheral nerve sheath tumor, myxofibrosarcoma, sarcoma with unspecified histotype, and synovial sarcoma [32]. TMA blocks included two to three 1-mm diameter core punches from each tumor sample.…”

Section: Patient Cohort and Selection Criteriamentioning

confidence: 99%

PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma

Toivanen,

Kilpinen,

Ojala

et al. 2023

Cancers

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Liposarcomas (LPSs) are a heterogeneous group of malignancies that arise from adipose tissue. Although LPSs are among the most common soft-tissue sarcoma subtypes, precision medicine treatments are not currently available. To discover LPS-subtype-specific therapy targets, we investigated RNA sequenced transcriptomes of 131 clinical LPS tissue samples and compared the data with a transcriptome database that contained 20,218 samples from 95 healthy tissues and 106 cancerous tissue types. The identified genes were referred to the NCATS BioPlanet library with Enrichr to analyze upregulated signaling pathways. PDE3A protein expression was investigated with immunohistochemistry in 181 LPS samples, and PDE3A and SLFN12 mRNA expression with RT-qPCR were investigated in 63 LPS samples. Immunoblotting and cell viability assays were used to study LPS cell lines and their sensitivity to PDE3A modulators. We identified 97, 247, and 37 subtype-specific, highly expressed genes in dedifferentiated, myxoid, and pleomorphic LPS subtypes, respectively. Signaling pathway analysis revealed a highly activated hedgehog signaling pathway in dedifferentiated LPS, phospholipase c mediated cascade and insulin signaling in myxoid LPS, and pathways associated with cell proliferation in pleomorphic LPS. We discovered a strong association between high PDE3A expression and myxoid LPS, particularly in high-grade tumors. Moreover, myxoid LPS samples showed elevated expression levels of SLFN12 mRNA. In addition, PDE3A- and SLFN12-coexpressing LPS cell lines SA4 and GOT3 were sensitive to PDE3A modulators. Our results indicate that PDE3A modulators are promising drugs to treat myxoid LPS. Further studies are required to develop these drugs for clinical use.

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A performance evaluation of drug response prediction models for individual drugs

Park¹,

Lee²,

Nam³

2023

Sci Rep

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Drug response prediction is important to establish personalized medicine for cancer therapy. Model construction for predicting drug response (i.e., cell viability half-maximal inhibitory concentration [IC50]) of an individual drug by inputting pharmacogenomics in disease models remains critical. Machine learning (ML) has been predominantly applied for prediction, despite the advent of deep learning (DL). Moreover, whether DL or traditional ML models are superior for predicting cell viability IC50s has to be established. Herein, we constructed ML and DL drug response prediction models for 24 individual drugs and compared the performance of the models by employing gene expression and mutation profiles of cancer cell lines as input. We observed no significant difference in drug response prediction performance between DL and ML models for 24 drugs [root mean squared error (RMSE) ranging from 0.284 to 3.563 for DL and from 0.274 to 2.697 for ML; R2 ranging from −7.405 to 0.331 for DL and from −8.113 to 0.470 for ML]. Among the 24 individual drugs, the ridge model of panobinostat exhibited the best performance (R2 0.470 and RMSE 0.623). Thus, we selected the ridge model of panobinostat for further application of explainable artificial intelligence (XAI). Using XAI, we further identified important genomic features for panobinostat response prediction in the ridge model, suggesting the genomic features of 22 genes. Based on our findings, results for an individual drug employing both DL and ML models were comparable. Our study confirms the applicability of drug response prediction models for individual drugs.

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Tensin2 Is a Novel Diagnostic Marker in GIST, Associated with Gastric Location and Non-Metastatic Tumors

Cited by 4 publications

References 42 publications

The molecular and clinical role of Tensin 1/2/3 in cancer

The molecular and clinical role of Tensin 1/2/3 in cancer

PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma

A performance evaluation of drug response prediction models for individual drugs

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