Combined RNA/tissue profiling identifies novel Cancer/testis genes

Jamin, Soazik P.; Hikmet, Feria; Mathiéu, Romain; Jégou, Bernard; Lindskog, Cecilia; Chalmel, Frédéric; Primig, Michael

doi:10.1002/1878-0261.12900

Cited by 6 publications

(7 citation statements)

References 85 publications

(137 reference statements)

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“…Observations of the testes of PDCL2 -knockout mice revealed the loss of sperm acrosomal cap formation and malformed nuclei. It has also been reported that the PDCL2 protein is associated with the decreased survival of kidney cancer patients ( 31 ).…”

Section: Discussionmentioning

confidence: 94%

Identification of PDCL2 as a candidate marker in Sertoli cell-only syndrome by chromatin immunoprecipitation-sequencing and bioinformatics analysis

Yu¹,

Qin²,

Wu³

et al. 2023

Transl Androl Urol

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Background Sertoli cell-only syndrome (SCOS) or germ cell aplasia is one of the most serious histopathological subtypes within the scope of non-obstructive azoospermia (NOA). Understanding the molecular mechanism of SCOS and identifying new non-invasive markers for clinical application is crucial to guide proper sperm procurement and avoid unnecessary interventions. This study sought to identify the differentially expressed genes (DEGs) of SCOS by using gene sequencing identity and verify the key marker genes to provide basic data for subsequent research on SCOS. Methods A total of 50 testicular samples were collected in this study from 25 patients with SCOS and 25 patients with normal spermatogenesis. In total, 5 pairs of testis samples were used for the RNA-sequencing (RNA-seq). We identified the DEGs between the SCOS and normal spermatogenesis patients and conducted a Gene Ontology (GO) analysis and a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The expression of the main target gene phosducin-like 2 ( PDCL2 ) was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Results In total, 3,133 upregulated DEGs and 1,406 downregulated DEGs were identified by the RNA-seq. The highly enriched processes involved in spermatogenesis included the mitotic cell cycle, cell cycle, and oocyte maturation. The expression of PDCL2 was verified as a downregulation marker in SCOS by qRT-PCR and IHC. Conclusions This study identified the DEGs of SCOS, and the bioinformatics analysis results identified the potential target key genes and pathways for SCOS. PDCL2 is a key gene involved in SCOS and may serve as a non-invasive downregulation marker of SCOS.

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Section: Discussionmentioning

confidence: 94%

Identification of PDCL2 as a candidate marker in Sertoli cell-only syndrome by chromatin immunoprecipitation-sequencing and bioinformatics analysis

Yu¹,

Qin²,

Wu³

et al. 2023

Transl Androl Urol

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“…Furthermore, SPESP1 knockdown induced cell senescence and accelerated skin ageing. While previous studies have linked SPESP1 to the growth and development of tumour diseases, 20 , 40 , 41 , 42 there remains a limited understanding of the functional roles and underlying mechanisms of SPESP1.…”

Section: Discussionmentioning

confidence: 99%

Downregulated SPESP1‐driven fibroblast senescence decreases wound healing in aged mice

Zhong,

Zhou,

Guo

et al. 2024

Clinical & Translational Med

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BackgroundHuman dermal fibroblasts (HDFs) are essential in the processes of skin ageing and wound healing. However, the underlying mechanism of HDFs in skin healing of the elderly has not been well defined. This study aims to elucidate the mechanisms of HDFs senescence and how senescent HDFs affect wound healing in aged skin.MethodsThe expression and function of sperm equatorial segment protein 1 (SPESP1) in skin ageing were evaluated via in vivo and in vitro experiments. To delve into the potential molecular mechanisms by which SPESP1 influences skin ageing, a combination of techniques was employed, including proteomics, RNA sequencing, immunoprecipitation, chromatin immunoprecipitation and liquid chromatography‐mass spectrometry analyses. Clearance of senescent cells by dasatinib plus quercetin (D+Q) was investigated to explore the role of SPESP1‐induced senescent HDFs in wound healing.ResultsHere, we define the critical role of SPESP1 in ameliorating HDFs senescence and retarding the skin ageing process. Mechanistic studies demonstrate that SPESP1 directly binds to methyl‐binding protein, leading to Decorin demethylation and subsequently upregulation of its expression. Moreover, SPESP1 knockdown delays wound healing in young mice and SPESP1 overexpression induces wound healing in old mice. Notably, pharmacogenetic clearance of senescent cells by D+Q improved wound healing in SPESP1 knockdown skin.ConclusionsTaken together, these findings reveal the critical role of SPESP1 in skin ageing and wound healing, expecting to facilitate the development of anti‐ageing strategies and improve wound healing in the elderly.

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“…Molecular biology and genomic approaches have led to the discovery of several hundred cancer testis genes, most of which are identified using gene expression on the mRNA level (mRNA expression described further in the text). However, the gene expression on the protein level (protein expression described further in the text) in the testis is still unclear, and the human protein atlas (HPA) has been used as a reference to determine the testicular proteome [25]. The HPA is a free-to-use and open-access platform with the aim of mapping all the human proteins in the body.…”

Section: Introductionmentioning

confidence: 99%

Testicular Germ Cell Tumor Tissue Biomarker Analysis: A Comparison of Human Protein Atlas and Individual Testicular Germ Cell Tumor Component Immunohistochemistry

Krasic,

Skara Abramovic,

Himelreich Peric

et al. 2023

Cells

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The accurate management of testicular germ cell tumors (TGCTs) depends on identifying the individual histological tumor components. Currently available data on protein expression in TGCTs are limited. The human protein atlas (HPA) is a comprehensive resource presenting the expression and localization of proteins across tissue types and diseases. In this study, we have compared the data from the HPA with our in-house immunohistochemistry on core TGCT diagnostic genes to test reliability and potential biomarker genes. We have compared the protein expression of 15 genes in TGCT patients and non-neoplastic testicles with the data from the HPA. Protein expression was converted into diagnostic positivity. Our study discovered discrepancies in three of the six core TGCT diagnostic genes, POU5F1, KIT and SOX17 in HPA. DPPA3, CALCA and TDGF1 were presented as potential novel TGCT biomarkers. MGMT was confirmed while RASSF1 and PRSS21 were identified as biomarkers of healthy testicular tissue. Finally, SALL4, SOX17, RASSF1 and PRSS21 dysregulation in the surrounding testicular tissue with complete preserved spermatogenesis of TGCT patients was detected, a potential early sign of neoplastic transformation. We highlight the importance of a multidisciplinary collaborative approach to fully understand the protein landscape of human testis and its pathologies.

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Combined RNA/tissue profiling identifies novel Cancer/testis genes

Cited by 6 publications

References 85 publications

Identification of PDCL2 as a candidate marker in Sertoli cell-only syndrome by chromatin immunoprecipitation-sequencing and bioinformatics analysis

Identification of PDCL2 as a candidate marker in Sertoli cell-only syndrome by chromatin immunoprecipitation-sequencing and bioinformatics analysis

Downregulated SPESP1‐driven fibroblast senescence decreases wound healing in aged mice

Testicular Germ Cell Tumor Tissue Biomarker Analysis: A Comparison of Human Protein Atlas and Individual Testicular Germ Cell Tumor Component Immunohistochemistry

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