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

Lundgren, Sebastian LU ; Fagerström-Vahman, Helena ; Zhang, Cheng ; Ben-Dror, Liv LU ; Mardinoglu, Adil ; Uhlen, Mathias ; Nodin, Björn LU and Jirström, Karin LU (2019) In Biomarker research 7(1).
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... (More)

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.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
KIRREL, Melanoma, NEPH1, Prognosis
in
Biomarker research
volume
7
issue
1
article number
1
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85062927349
  • pmid:30675360
ISSN
2050-7771
DOI
10.1186/s40364-018-0153-8
language
English
LU publication?
yes
id
f318b2c5-ec73-4897-9a90-3cc6e781743c
date added to LUP
2019-03-28 13:34:34
date last changed
2021-01-06 07:58:41
@article{f318b2c5-ec73-4897-9a90-3cc6e781743c,
  abstract     = {<p>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.</p>},
  author       = {Lundgren, Sebastian and Fagerström-Vahman, Helena and Zhang, Cheng and Ben-Dror, Liv and Mardinoglu, Adil and Uhlen, Mathias and Nodin, Björn and Jirström, Karin},
  issn         = {2050-7771},
  language     = {eng},
  month        = {01},
  number       = {1},
  publisher    = {BioMed Central (BMC)},
  series       = {Biomarker research},
  title        = {Discovery of KIRREL as a biomarker for prognostic stratification of patients with thin melanoma 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis},
  url          = {http://dx.doi.org/10.1186/s40364-018-0153-8},
  doi          = {10.1186/s40364-018-0153-8},
  volume       = {7},
  year         = {2019},
}