SMAD7 is a novel independent predictor of survival in patients with cutaneous melanoma

Kaczorowski, Maciej; Biecek, Przemysław; Donizy, Piotr; Pieniążek, Małgorzata; Matkowski, Rafał; Hałoń, Agnieszka

doi:10.1016/j.trsl.2018.09.002

Cited by 10 publications

(7 citation statements)

References 31 publications

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“…In recent years, inhibitors targeting TGF-β pathway have been discovered and investigated by pharmaceutical companies for cancer therapy, and some of them are in clinical trial now, such as Phase I study of GC1008 (fresolimumab), Ph II study of NCT01453361 (Gemogenovatucel-T) and so on [58,59]. In 2019, Kaczorowski et al [60] suggested that overexpression of SMAD7 may be a new hallmark inhibitor of TGF-β in melanoma. In 2021, Liu et al [61] proposed a triple combination therapy with PD-1/PD-L1, BRAF, and MEK inhibitor in stage III-IV melanoma as significantly improving PFS of patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of Immune Function-Related Subtypes in Cutaneous Melanoma

Liu

Zhu

Jin

et al. 2021

Life

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Tumour immunotherapy combined with molecular typing is a new therapy to help select patients. However, molecular typing algorithms related to tumour immune function have not been thoroughly explored. We herein proposed a single sample immune signature network (SING) method to identify new immune function-related subtypes of cutaneous melanoma of the skin. A sample-specific network and tumour microenvironment were constructed based on the immune annotation of cutaneous melanoma samples. Then, the differences and heterogeneity of immune function among different subtypes were analysed and verified. A total of 327 cases of cutaneous melanoma were divided into normal and immune classes; the immune class had more immune enrichment characteristics. After further subdividing the 327 cases into three immune-related subtypes, the degree of immune enrichment in the “high immune subtype” was greater than that in other subtypes. Similar results were validated in both tumour samples and cell lines. Sample-specific networks and the tumour microenvironment based on immune annotation contribute to the mining of cutaneous melanoma immune function-related subtypes. Mutations in B2M and PTEN are considered potential therapeutic targets that can improve the immune response. Patients with a high immune subtype can generally obtain a better immune prognosis effect, and the prognosis may be improved when combined with TGF-β inhibitors.

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Section: Discussionmentioning

confidence: 99%

Identification of Immune Function-Related Subtypes in Cutaneous Melanoma

Liu

Zhu

Jin

et al. 2021

Life

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“…The semi-quantitative scale of Remmele and Stegner (26) combining two parameters of immunohistochemical reaction, i.e. the percentage of reactive tissue and staining intensity, was modified by the authors and employed as described previously for evaluation of immunoexpression in tumor cells (27). In brief, 0-3 points were given for the intensity of reaction and 0-10 points were given (0%: 0 points, 1-10%: 1 point, 11-20%: 2 points, etc.)…”

Section: Methodsmentioning

confidence: 99%

ROCK1 and ROCK2 Are Down-regulated in Aggressive and Advanced Skin Melanomas – A Clinicopathological Perspective

et al. 2020

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Background: RhoA and its downstream effectors Rho-associated coiled-coil kinases (ROCK) 1 and 2 are central controllers of cytoskeleton dynamics, and therefore influence cell shape, adhesion and migration. Since modulation of these processes holds promise for an effective anticancer strategy, effects of ROCK inhibition have been evaluated in a number of malignancies. Materials and Methods: Using immunohistochemistry, ROCK1 and ROCK2 expression was semi-quantitatively assessed in 129 patientderived primary melanomas. Results: There was a striking predilection for low melanocytic expression of both kinases in thick, ulcerated and mitogenic tumors, as well as in nodular histological type. ROCK1 and-2 expression in tumor-infiltrating lymphocytes (TILs) was preferentially down-regulated in advanced and aggressive tumors. Moreover, diminished ROCK2 reactivity in melanoma cells and TILs was associated with shorter melanoma-specific and recurrence-free survival. Conclusion: This is the first analysis of ROCK1 and-2 protein expression in clinical melanoma samples and the results indicated the suppression of ROCK signaling in melanocytes of aggressive and late-stage tumors. Functional models that more accurately represent the clinical setting are necessary to dissect the role of ROCK1 and-2 in melanoma. Additionally, our study indicates that ROCK activity in TILs may be involved in the pathogenesis of cancer, and thus merits further investigations.

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“…Kaczorowski et al [ 37 ] measured the expression of Smad7 in 205 patients with skin melanoma and found that expression was closely related to invasive tumor phenotypes, such as ulcerated tumors and tumors with a higher thickness and mitotic rates. However, no regional or distant metastases were observed.…”

Section: Smad7 In Cancermentioning

confidence: 99%

Expression and function of Smad7 in autoimmune and inflammatory diseases

et al. 2021

J Mol Med

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Transforming growth factor-β (TGF-β) plays a critical role in the pathological processes of various diseases. However, the signaling mechanism of TGF-β in the pathological response remains largely unclear. In this review, we discuss advances in research of Smad7, a member of the I-Smads family and a negative regulator of TGF-β signaling, and mainly review the expression and its function in diseases. Smad7 inhibits the activation of the NF-κB and TGF-β signaling pathways and plays a pivotal role in the prevention and treatment of various diseases. Specifically, Smad7 can not only attenuate growth inhibition, fibrosis, apoptosis, inflammation, and inflammatory T cell differentiation, but also promotes epithelial cells migration or disease development. In this review, we aim to summarize the various biological functions of Smad7 in autoimmune diseases, inflammatory diseases, cancers, and kidney diseases, focusing on the molecular mechanisms of the transcriptional and posttranscriptional regulation of Smad7.

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SMAD7 is a novel independent predictor of survival in patients with cutaneous melanoma

Cited by 10 publications

References 31 publications

Identification of Immune Function-Related Subtypes in Cutaneous Melanoma

Identification of Immune Function-Related Subtypes in Cutaneous Melanoma

ROCK1 and ROCK2 Are Down-regulated in Aggressive and Advanced Skin Melanomas – A Clinicopathological Perspective

Expression and function of Smad7 in autoimmune and inflammatory diseases

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