The Prognostic Relevance of PMCA4 Expression in Melanoma : Gender Specificity and Implications for Immune Checkpoint Inhibition

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Fältnamn	Indikatorer	Metadata
000		05005naa a2200553 4500
001		oai:lup.lub.lu.se:695e7f0b-f11e-4c74-a312-511f73b0e63d
003		SwePub
008		220609s2022 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://lup.lub.lu.se/record/695e7f0b-f11e-4c74-a312-511f73b0e63d2 URI
024	7	a https://doi.org/10.3390/ijms230633242 DOI
040		a (SwePub)lu
041		a engb eng
042		9 SwePub
072	7	a art2 swepub-publicationtype
072	7	a ref2 swepub-contenttype
100	1	a Hegedüs, Lucau Ruhrlandklinik4 aut
245	1 0	a The Prognostic Relevance of PMCA4 Expression in Melanoma : Gender Specificity and Implications for Immune Checkpoint Inhibition
264		c 2022-03-19
264	1	b MDPI AG,c 2022
520		a PMCA4 is a critical regulator of Ca2+ homeostasis in mammalian cells. While its biological and prognostic relevance in several cancer types has already been demonstrated, only preclinical investigations suggested a metastasis suppressor function in melanoma. Therefore, we studied the expression pattern of PMCA4 in human skin, nevus, as well as in primary and metastatic melanoma using immunohistochemistry. Furthermore, we analyzed the prognostic power of PMCA4 mRNA levels in cutaneous melanoma both at the non-metastatic stage as well as after PD-1 blockade in advanced disease. PMCA4 localizes to the plasma membrane in a differentiation dependent manner in human skin and mucosa, while nevus cells showed no plasma membrane staining. In contrast, primary cutaneous, choroidal and conjunctival melanoma cells showed specific plasma membrane localization of PMCA4 with a wide range of intensities. Analyzing the TCGA cohort, PMCA4 mRNA levels showed a gender specific prognostic impact in stage I–III melanoma. Female patients with high transcript levels had a significantly longer progression-free survival. Melanoma cell specific PMCA4 protein expression is associated with anaplasticity in melanoma lung metastasis but had no impact on survival after lung metastasectomy. Importantly, high PMCA4 transcript levels derived from RNA-seq of cutaneous melanoma are associated with significantly longer overall survival after PD-1 blockade. In summary, we demonstrated that human melanoma cells express PMCA4 and PMCA4 transcript levels carry prognostic information in a gender specific manner.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Cell- och molekylärbiologi0 (SwePub)301082 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Cell and Molecular Biology0 (SwePub)301082 hsv//eng
653		a Immune checkpoint inhibition
653		a Lung metastasis
653		a Melanoma
653		a Plasma membrane calcium ATPase 4
700	1	a Livingstone, Elisabethu University of Duisburg-Essen4 aut
700	1	a Bánkfalvi, Ágnesu University of Duisburg-Essen4 aut
700	1	a Viehof, Janu University of Duisburg-Essen4 aut
700	1	a Enyedi, Ágnesu Semmelweis University4 aut
700	1	a Bilecz, Ágnesu Semmelweis University4 aut
700	1	a Győrffy, Balázsu Semmelweis University4 aut
700	1	a Baranyi, Marcellu Semmelweis University4 aut
700	1	a Tőkés, Anna Máriau Semmelweis University4 aut
700	1	a Gil, Jeovanisu Lund University,Lunds universitet,Medicinsk onkologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Medical oncology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments4 aut0 (Swepub:lu)je2062gi
700	1	a Marko-Varga, Györgyu Lund University,Lunds universitet,Avdelningen för Biomedicinsk teknik,Institutionen för biomedicinsk teknik,Institutioner vid LTH,Lunds Tekniska Högskola,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Department of Biomedical Engineering,Departments at LTH,Faculty of Engineering, LTH,Lund University Research Groups4 aut0 (Swepub:lu)akem-gmv
700	1	a Griewank, Klaus G.u University of Duisburg-Essen4 aut
700	1	a Zimmer, Lisau University of Duisburg-Essen4 aut
700	1	a Váraljai, Renátau University of Duisburg-Essen4 aut
700	1	a Sucker, Antjeu University of Duisburg-Essen4 aut
700	1	a Zaremba, Anneu University of Duisburg-Essen4 aut
700	1	a Schadendorf, Dirku University of Duisburg-Essen4 aut
700	1	a Aigner, Clemensu University of Duisburg-Essen4 aut
700	1	a Hegedüs, Balázsu University of Duisburg-Essen4 aut
710	2	a Ruhrlandklinikb University of Duisburg-Essen4 org
773	0	t International Journal of Molecular Sciencesd : MDPI AGg 23:6q 23:6x 1661-6596x 1422-0067
856	4	u http://dx.doi.org/10.3390/ijms23063324x freey FULLTEXT
856	4 8	u https://lup.lub.lu.se/record/695e7f0b-f11e-4c74-a312-511f73b0e63d
856	4 8	u https://doi.org/10.3390/ijms23063324

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