Discovery of KIRREL as a biomarker for prognostic stratification of patients with thin melanoma 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis

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Lundgren, SebastianLund University,Lunds universitet,Personlig patologi och cancerbehandling,Forskargrupper vid Lunds universitet,Personalized Pathology & Cancer Therapy,Lund University Research Groups (author)

Discovery of KIRREL as a biomarker for prognostic stratification of patients with thin melanoma 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis

Article/chapterEnglish2019

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2019-01-14
Springer Science and Business Media LLC,2019

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LIBRIS-ID:oai:lup.lub.lu.se:f318b2c5-ec73-4897-9a90-3cc6e781743c
https://lup.lub.lu.se/record/f318b2c5-ec73-4897-9a90-3cc6e781743cURI
https://doi.org/10.1186/s40364-018-0153-8DOI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype

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There is a great unmet clinical need to identify patients with thin primary cutaneous melanomas (T1, Breslow thickness ≤ 1 mm) who have a high risk for tumour recurrence and death from melanoma. Kin of IRRE-like protein 1 (KIRREL/NEPH1) is expressed in podocytes and involved in glomerular filtration. Screening in the Human Protein Atlas portal revealed a particularly high expression of KIRREL in melanoma, both at the mRNA and protein levels. In this study, we followed up on these findings and examined the prognostic value of KIRREL in a population-based cohort. Immunohistochemical expression of KIRREL was examined in tissue microarrays with a subset of primary tumours and paired lymph node metastases from an original cohort of 268 incident cases of melanoma in the Malmö Diet and Cancer study. KIRREL mRNA expression was examined in 103 melanoma cases in The Cancer Genome Atlas (TCGA). Membranous/cytoplasmic expression of KIRREL was detected in 158/185 (85.4%) primary tumours and 18/19 (94.7%) metastases. High expression of KIRREL was significantly associated with several unfavourable clinicopathological factors. High KIRREL protein expression was an independent factor of reduced recurrence free and melanoma specific survival, particularly in thin melanomas, even outperforming absolute thickness and ulceration (HR = 30.85; 95% CI 1.54-616.36 and HR = 6.32 95% CI 1.19-33.65). High mRNA levels of KIRREL were not significantly associated with survival in TCGA. In conclusion, KIRREL is not only a novel potential diagnostic marker for melanoma, but may also be a useful prognostic biomarker for improved stratification of patients with thin melanoma. These findings may be of high clinical relevance and therefore merit further validation.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
KIRREL
Melanoma
NEPH1
Prognosis

Added entries (persons, corporate bodies, meetings, titles ...)

Fagerström-Vahman, HelenaLund University (author)
Zhang, ChengKTH Royal Institute of Technology (author)
Ben-Dror, LivLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-lvj (author)
Mardinoglu, AdilKTH Royal Institute of Technology (author)
Uhlen, MathiasKTH Royal Institute of Technology (author)
Nodin, BjörnLund University,Lunds universitet,Personlig patologi och cancerbehandling,Forskargrupper vid Lunds universitet,Personalized Pathology & Cancer Therapy,Lund University Research Groups(Swepub:lu)immu-bnn (author)
Jirström, KarinLund University,Lunds universitet,Personlig patologi och cancerbehandling,Forskargrupper vid Lunds universitet,Personalized Pathology & Cancer Therapy,Lund University Research Groups(Swepub:lu)pat-kji (author)
Personlig patologi och cancerbehandlingForskargrupper vid Lunds universitet (creator_code:org_t)

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