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Discovery of KIRREL as a biomarker for prognostic stratification of patients with thin melanoma

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Discovery of KIRREL as a biomarker for prognostic stratification of patients with thin melanoma. / Lundgren, Sebastian; Fagerstrom-Vahman, Helena; Zhang, Cheng; Ben-Dror, Liv; Mardinoglu, Adil; Uhlen, Mathias; Nodin, Bjorn; Jirstrom, Karin.

In: BIOMARKER RESEARCH, Vol. 7, No. 1, 1, 14.01.2019.

Research output: Contribution to journalArticle

Harvard

Lundgren, S, Fagerstrom-Vahman, H, Zhang, C, Ben-Dror, L, Mardinoglu, A, Uhlen, M, Nodin, B & Jirstrom, K 2019, 'Discovery of KIRREL as a biomarker for prognostic stratification of patients with thin melanoma', BIOMARKER RESEARCH, vol. 7, no. 1, 1. https://doi.org/10.1186/s40364-018-0153-8

APA

Lundgren, S., Fagerstrom-Vahman, H., Zhang, C., Ben-Dror, L., Mardinoglu, A., Uhlen, M., ... Jirstrom, K. (2019). Discovery of KIRREL as a biomarker for prognostic stratification of patients with thin melanoma. BIOMARKER RESEARCH, 7(1), [1]. https://doi.org/10.1186/s40364-018-0153-8

Vancouver

Lundgren S, Fagerstrom-Vahman H, Zhang C, Ben-Dror L, Mardinoglu A, Uhlen M et al. Discovery of KIRREL as a biomarker for prognostic stratification of patients with thin melanoma. BIOMARKER RESEARCH. 2019 Jan 14;7(1). 1. https://doi.org/10.1186/s40364-018-0153-8

Author

Lundgren, Sebastian ; Fagerstrom-Vahman, Helena ; Zhang, Cheng ; Ben-Dror, Liv ; Mardinoglu, Adil ; Uhlen, Mathias ; Nodin, Bjorn ; Jirstrom, Karin. / Discovery of KIRREL as a biomarker for prognostic stratification of patients with thin melanoma. In: BIOMARKER RESEARCH. 2019 ; Vol. 7, No. 1.

Bibtex Download

@article{289a4048d2d5497da766a9a5aa0f1b63,
title = "Discovery of KIRREL as a biomarker for prognostic stratification of patients with thin melanoma",
abstract = "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 Malm{\"o} 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.",
keywords = "KIRREL, Melanoma, NEPH1, Prognosis",
author = "Sebastian Lundgren and Helena Fagerstrom-Vahman and Cheng Zhang and Liv Ben-Dror and Adil Mardinoglu and Mathias Uhlen and Bjorn Nodin and Karin Jirstrom",
year = "2019",
month = "1",
day = "14",
doi = "10.1186/s40364-018-0153-8",
language = "English",
volume = "7",
journal = "BIOMARKER RESEARCH",
issn = "2050-7771",
publisher = "BioMed Central Ltd.",
number = "1",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Discovery of KIRREL as a biomarker for prognostic stratification of patients with thin melanoma

AU - Lundgren, Sebastian

AU - Fagerstrom-Vahman, Helena

AU - Zhang, Cheng

AU - Ben-Dror, Liv

AU - Mardinoglu, Adil

AU - Uhlen, Mathias

AU - Nodin, Bjorn

AU - Jirstrom, Karin

PY - 2019/1/14

Y1 - 2019/1/14

N2 - 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.

AB - 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.

KW - KIRREL

KW - Melanoma

KW - NEPH1

KW - Prognosis

UR - http://www.scopus.com/inward/record.url?scp=85062927349&partnerID=8YFLogxK

U2 - 10.1186/s40364-018-0153-8

DO - 10.1186/s40364-018-0153-8

M3 - Article

VL - 7

JO - BIOMARKER RESEARCH

JF - BIOMARKER RESEARCH

SN - 2050-7771

IS - 1

M1 - 1

ER -

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