Multiple Skin Squamous Cell Carcinomas in Junctional Epidermolysis Bullosa Due to Altered Laminin-332 Function

Fortugno, Paola; Condorelli, Angelo Giuseppe; Dellambra, Elena; Guerra, Liliana; Cianfarani, Francesca; Tinaburri, Lavinia; Proto, Vittoria; Luca, Naomi De; Passarelli, Francesca; Ricci, Francesca; Zambruno, Giovanna; Castiglia, Daniele

doi:10.3390/ijms21041426

Cited by 5 publications

(4 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A whole-exome sequencing of both probands identi ed novel heterozygous mutations in the last exon of LAMB3 that likely truncated the protein (23). The accumulation of mutant laminin-332 contributed to invasiveness and recurrence of squamous cell carcinoma (24). Together with our addition, we found more LAMBs gene mutation types in different tumor progression, which can be used as a prognostic factor of pan cancer.…”

Section: Discussionsupporting

confidence: 52%

Integrative analysis the characterization of LAMBs in predicting the prognosis and the immunotherapy response of cancers

Tao

Yuan

Shi

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: Laminin subunit betas (LAMBs) are the major noncollagenous constituent of basement membranes that implicated in biological functions such as cell adhesion, metastasis. However, few studies have systematically analyzed the prognostic value and immune characteristics of LAMBs in pan-cancer types. Methods: A pan-cancer comprehensive analysis of LAMBs in expression levels, protein localization, structure, mutations and methylation were explored. Next, Cox regression and Kaplan-Meier method were applied to analyze the prognostic role of LAMBs in pan-cancer. Protein-Protein Interaction (PPI) analysis was performed in the GeneMANIA database, and enrichment analysis was predicted signaling pathways were identifified by using Gene Ontology (GO), Kyoto Encyclopedia of Genes (KEGG) and gene set variation analysis (GSVA) analysis. The immune characteristics of LAMBs in the tumor microenvironment were evaluated via ImmuCellAI and TIMER 2.0. was the main platform to investigate the tumor associated macrophages (TAMs) related to LAMBs in pan-cancer, especially M2-like TAMs. In addition, single-cell sequencing analysis and tracking tumor immunophenotype (TIP) were also conducted to validate the interaction immune role of LAMBs with macrophages in cancers. Furthermore, the immunoregulators, tumour mutational burden (TMB) and microsatellite instability (MSI) was performed to evaluate the immune response role of LAMBs in cancers. Finally, the immunotherapy response and drug sensitive small molecule drugs based on LAMBs expression were predicted. Results: The expression, mutation and methylation of LAMBs was aberrantly expressed in most cancer types and exhibited prognosis predictive ability in various cancers. In addition, our results also showed that LAMBs was signifificantly correlated with immune-activated (including pathways and biological processes), immune cell infifiltrations, immunoregulator expressions, TMB and MSI. Importantly, analysis of an independent immunotherapy cohorts revealed that low-risk patients had better immunotherapy responses and prognosis than high-risk patients in some cancers. Furthermore, the immunotherapy response and sensitive small molecule drugs which correlate with LAMBs expression in different cancer types, had a potent capability to predict immunotherapy response in pan-cancers. Conclusions: LAMBs expression may contribute to increased infiltration of TAMs, which not only acted as a potent prognostic factor to predict the clinical outcomes of cancer patients but was also a promising immunotherapy predictive biomarker for cancer patients treated with immune-checkpoint inhibitors (ICIs).

show abstract

Section: Discussionsupporting

confidence: 52%

Integrative analysis the characterization of LAMBs in predicting the prognosis and the immunotherapy response of cancers

Tao

Yuan

Shi

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Genotype–phenotype correlations drawn from published cases with localized or intermediate JEB phenotypes predict that LM332 chain mutations allowing the synthesis and secretion of reduced or even normal amounts of the mutant heterotrimeric molecule prevent early lethality and are compatible with normal life expectancy [ 5 ]. In the large majority of cases, such mutations affect splice sites or codon sequence and cause in-frame deletions or single amino acid changes in LM332 subdomains [ 6 , 7 , 8 , 9 , 20 ]. In frame deletions within the coiled coil domain always spare the LM332 C-terminal ends that comprise sequences crucial for heterotrimer assembly and stabilization [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…The amount of LM332 produced by epithelial cells with pathogenic variants in the LAMA3 , LAMB3 or LAMC2 genes is the major determinant of JEB phenotype severity [ 5 ]. The severe JEB subtype results from absent LM332, while intermediate or localized JEB forms associate with variably reduced or even normal amounts of mutant LM332 [ 6 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

A Novel Phenotype of Junctional Epidermolysis Bullosa with Transient Skin Fragility and Predominant Ocular Involvement Responsive to Human Amniotic Membrane Eyedrops

Castiglia

Fortugno

Condorelli

et al. 2021

Genes

Self Cite

View full text Add to dashboard Cite

Junctional epidermolysis bullosa (JEB) is a clinically and genetically heterogeneous skin fragility disorder frequently caused by mutations in genes encoding the epithelial laminin isoform, laminin-332. JEB patients also present mucosal involvement, including painful corneal lesions. Recurrent corneal abrasions may lead to corneal opacities and visual impairment. Current treatments are merely supportive. We report a novel JEB phenotype distinguished by the complete resolution of skin fragility in infancy and persistent ocular involvement with unremitting and painful corneal abrasions. Biallelic LAMB3 mutations c.3052-5C>G and c.3492_3493delCG were identified as the molecular basis for this phenotype, with one mutation being a hypomorphic splice variant that allows residual wild-type laminin-332 production. The reduced laminin-332 level was associated with impaired keratinocyte adhesion. Then, we also investigated the therapeutic power of a human amniotic membrane (AM) eyedrop preparation for corneal lesions. AM were isolated from placenta donors, according to a procedure preserving the AM biological characteristics as a tissue, and confirmed to contain laminin-332. We found that AM eyedrop preparation could restore keratinocyte adhesion in an in vitro assay. Of note, AM eyedrop administration to the patient resulted in long-lasting remission of her ocular manifestations. Our findings suggest that AM eyedrops could represent an effective, non-invasive, simple-to-handle treatment for corneal lesions in patients with JEB and possibly other EB forms.

show abstract

“…For assessing the impact of and to establish the research directions for squamous cell carcinomas, we used the scientometric method [ 3 , 4 ]. A set of instructions was defined based on the keywords from the 76 articles we assessed [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , …”

Section: Methodsmentioning

confidence: 99%

Scientific Research Directions on the Histopathology and Immunohistochemistry of the Cutaneous Squamous Cell Carcinoma: A Scientometric Study

Cocuz

Repanovici

et al. 2022

Medicina

View full text Add to dashboard Cite

Introduction: Cutaneous squamous cell carcinoma (cSCC) is one of the most frequently occurring types of cancer in humans. Scientometric research is an innovative method for analyzing the research trends in various domains, with great implications in the field of medicine. Materials and Methods: We searched the Web of Science database with the following established query terms: “Squamous cell carcinoma”, “skin”, and “immunohistochemistry”. After applying the inclusion and exclusion criteria, a total of 76 articles were selected. The present study aims to analyze, based on the frequency of use of keywords with scientometric algorithms and map-based distributions, the trends of the research concerning cSCCs in 2017–2022. Results: A graphical representation based on 11 scientometric maps presented the division of the keywords into seven clusters, from which seven categories of research interest were defined. The clusters represent a multidisciplinary approach to the diagnosis and treatment of cSCCs, cancer diagnostics, patient outcomes, histopathological importance, management of cSCCs, role of progression, and adequate treatment of and importance of immunohistochemistry for cSCCs. The distribution of the citations shows the importance of the available research on cSCCs by analyzing the first five most-cited articles included in our study in direct concordance with the seven defined clusters. Conclusion: The scientometric research method reveals the interest of research in the multidisciplinary approach used to obtain the best outcomes for the patient, including a targeted investigation, as well as diagnostic and treatment options. The trends in the research reveal that histopathological diagnostics and immunohistochemistry, combined with molecular techniques, are the most important tools used to establish a personalized diagnosis, thus increasing the quality of life and life expectancy for patients with cSCCs.

show abstract

Multiple Skin Squamous Cell Carcinomas in Junctional Epidermolysis Bullosa Due to Altered Laminin-332 Function

Cited by 5 publications

References 38 publications

Integrative analysis the characterization of LAMBs in predicting the prognosis and the immunotherapy response of cancers

Integrative analysis the characterization of LAMBs in predicting the prognosis and the immunotherapy response of cancers

A Novel Phenotype of Junctional Epidermolysis Bullosa with Transient Skin Fragility and Predominant Ocular Involvement Responsive to Human Amniotic Membrane Eyedrops

Scientific Research Directions on the Histopathology and Immunohistochemistry of the Cutaneous Squamous Cell Carcinoma: A Scientometric Study

Contact Info

Product

Resources

About