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Publikationer (10 of 73) Visa alla publikationer
Herdenberg, C. & Hedman, H. (2023). Hypothesis: Do LRIG proteins regulate stem cell quiescence by promoting BMP signaling?. Stem Cell Reviews and Reports, 19(1), 59-66
Öppna denna publikation i ny flik eller fönster >>Hypothesis: Do LRIG proteins regulate stem cell quiescence by promoting BMP signaling?
2023 (Engelska)Ingår i: Stem Cell Reviews and Reports, ISSN 2629-3269, Vol. 19, nr 1, s. 59-66Artikel, forskningsöversikt (Refereegranskat) Published
Abstract [en]

Leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins are evolutionarily conserved integral membrane proteins. Mammalian LRIG1 regulates stem cell quiescence in various tissue compartments, including compartments in the epidermis, oral mucosa, intestines, neural system, and incisors. The planarian LRIG1 homolog regulates the quiescence of multipotent neoblasts. The mechanism through which LRIG proteins regulate stem cell quiescence has not been well documented, although it is generally assumed that LRIG1 regulates the epidermal growth factor receptor (EGFR) or other receptor tyrosine kinases. However, Lrig-null (Lrig1-/-;Lrig2-/-; and Lrig3-/-) mouse embryonic fibroblasts (MEFs) have been recently found to exhibit apparently normal receptor tyrosine kinase functions. Moreover, bone morphogenetic protein (BMP) signaling has been shown to depend on LRIG1 and LRIG3 expression. BMPs are well-known regulators of stem cell quiescence. Here, we hypothesize that LRIG1 might regulate stem cell quiescence by promoting BMP signaling.

HYPOTHESIS: Based on recent findings, it is hypothesized that LRIG1 regulates stem cell quiescence in mammalian tissues as well as in planarian neoblasts by promoting BMP signaling.

Ort, förlag, år, upplaga, sidor
Springer, 2023
Nyckelord
BMP, EGF, LRIG1, Quiescence, Stem cell
Nationell ämneskategori
Cancer och onkologi Cell- och molekylärbiologi
Identifikatorer
urn:nbn:se:umu:diva-198922 (URN)10.1007/s12015-022-10442-9 (DOI)000840596100002 ()35969315 (PubMedID)2-s2.0-85135895107 (Scopus ID)
Tillgänglig från: 2022-09-09 Skapad: 2022-09-09 Senast uppdaterad: 2023-01-11Bibliografiskt granskad
Abdullah Nasir, A., Herdenberg, C. & Hedman, H. (2023). Ligand-specific regulation of transforming growth factor beta superfamily factors by leucine-rich repeats and immunoglobulin-like domains proteins. PLOS ONE, 18(8), Article ID e0289726.
Öppna denna publikation i ny flik eller fönster >>Ligand-specific regulation of transforming growth factor beta superfamily factors by leucine-rich repeats and immunoglobulin-like domains proteins
2023 (Engelska)Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 18, nr 8, artikel-id e0289726Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Leucine-rich repeats and immunoglobulin-like domains (LRIG) are transmembrane proteins shown to promote bone morphogenetic protein (BMP) signaling in Caenorhabditis elegans, Drosophila melanogaster, and mammals. BMPs comprise a subfamily of the transforming growth factor beta (TGFβ) superfamily, or TGFβ family, of ligands. In mammals, LRIG1 and LRIG3 promote BMP4 signaling. BMP6 signaling, but not BMP9 signaling, is also regulated by LRIG proteins, although the specific contributions of LRIG1, LRIG2, and LRIG3 have not been investigated, nor is it known whether other mammalian TGFβ family members are regulated by LRIG proteins. To address these questions, we took advantage of Lrig-null mouse embryonic fibroblasts (MEFs) with doxycycline-inducible LRIG1, LRIG2, and LRIG3 alleles, which were stimulated with ligands representing all the major TGFβ family subgroups. By analyzing the signal mediators pSmad1/5 and pSmad3, as well as the induction of Id1 expression, we showed that LRIG1 promoted BMP2, BMP4, and BMP6 signaling and suppressed GDF7 signaling; LRIG2 promoted BMP2 and BMP4 signaling; and LRIG3 promoted BMP2, BMP4, BMP6, and GDF7 signaling. BMP9 and BMP10 signaling was not regulated by individual LRIG proteins, however, it was enhanced in Lrig-null cells. LRIG proteins did not regulate TGFβ1-induced pSmad1/5 signaling, or GDF11- or TGFβ1-induced pSmad3 signaling. Taken together, our results show that some, but not all, TGFβ family ligands are regulated by LRIG proteins and that the three LRIG proteins display differential regulatory effects. LRIG proteins thereby provide regulatory means for the cell to further diversify the signaling outcomes generated by a limited number of TGFβ family ligands and receptors.

Ort, förlag, år, upplaga, sidor
Public Library of Science (PLoS), 2023
Nationell ämneskategori
Cancer och onkologi
Identifikatorer
urn:nbn:se:umu:diva-214058 (URN)10.1371/journal.pone.0289726 (DOI)001055176800011 ()37603563 (PubMedID)2-s2.0-85168488332 (Scopus ID)
Forskningsfinansiär
Cancerfonden, 21 1583 PjKempestiftelserna, JCK-1829Umeå universitet, RV-967035Region Västerbotten, RV-967035
Tillgänglig från: 2023-09-06 Skapad: 2023-09-06 Senast uppdaterad: 2023-09-18Bibliografiskt granskad
Rosenbaum, A., Dahlin, A. M., Andersson, U., Björkblom, B., Wu, W.-Y. Y., Hedman, H., . . . Melin, B. S. (2023). Low-grade glioma risk SNP rs11706832 is associated with type I interferon response pathway genes in cell lines. Scientific Reports, 13, Article ID 6777.
Öppna denna publikation i ny flik eller fönster >>Low-grade glioma risk SNP rs11706832 is associated with type I interferon response pathway genes in cell lines
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2023 (Engelska)Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 13, artikel-id 6777Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Genome-wide association studies (GWAS) have contributed to our understanding of glioma susceptibility. To date, 25 risk loci for development of any of the glioma subtypes are known. However, GWAS studies reveal little about the molecular processes that lead to increased risk, especially for non-coding single nucleotide polymorphisms (SNP). A particular SNP in intron 2 of LRIG1, rs11706832, has been shown to increase the susceptibility for IDH1 mutated low-grade gliomas (LGG). Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is important in cancer development as it negatively regulates the epidermal growth factor receptor (EGFR); however, the mechanism responsible for this particular risk SNP and its potential effect on LRIG1 are not known. Using CRISPR-CAS9, we edited rs11706832 in HEK293T cells. Four HEK293T clones with the risk allele were compared to four clones with the non-risk allele for LRIG1 and SLC25A26 gene expression using RT-qPCR, for global gene expression using RNA-seq, and for metabolites using gas chromatography-mass spectrometry (GC–MS). The experiment did not reveal any significant effect of the SNP on the expression levels or splicing patterns of LRIG1 or SLC25A26. The global gene expression analysis revealed that the risk allele C was associated with upregulation of several mitochondrial genes. Gene enrichment analysis of 74 differentially expressed genes in the genome revealed a significant enrichment of type I interferon response genes, where many genes were downregulated for the risk allele C. Gene expression data of IDH1 mutated LGGs from the cancer genome atlas (TCGA) revealed a similar under expression of type I interferon genes associated with the risk allele. This study found the expression levels and splicing patterns of LRIG1 and SLC25A26 were not affected by the SNP in HEK293T cells. However, the risk allele was associated with a downregulation of genes involved in the innate immune response both in the HEK293T cells and in the LGG data from TCGA.

Ort, förlag, år, upplaga, sidor
Springer Nature, 2023
Nationell ämneskategori
Cancer och onkologi Medicinsk genetik
Identifikatorer
urn:nbn:se:umu:diva-208211 (URN)10.1038/s41598-023-33923-4 (DOI)000984494600021 ()37185361 (PubMedID)2-s2.0-85154566176 (Scopus ID)
Tillgänglig från: 2023-05-16 Skapad: 2023-05-16 Senast uppdaterad: 2023-09-05Bibliografiskt granskad
Lorenzzi Löfgren de Melo, A., Linder, A., Sundfeldt, K., Lindquist, D. & Hedman, H. (2022). Single-molecule array assay reveals the prognostic impact of plasma LRIG1 in ovarian carcinoma. Acta Oncologica, 61(11), 1425-1433
Öppna denna publikation i ny flik eller fönster >>Single-molecule array assay reveals the prognostic impact of plasma LRIG1 in ovarian carcinoma
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2022 (Engelska)Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 61, nr 11, s. 1425-1433Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Ovarian carcinoma is the eighth most common cause of cancer death in women worldwide. The disease is predominantly diagnosed at a late stage. This contributes to high recurrence rates, eventually leading to the development of treatment-resistant disease. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is a transmembrane protein that functions as a tumor suppressor and regulator of growth factor signaling. LRIG1 levels have not been investigated in human plasma previously.

Materials and methods: A quantitative LRIG1-specific single molecule array assay was developed and validated. LRIG1 levels were quantified in plasma samples from 486 patients with suspicious ovarian masses.

Results: Among women with ovarian carcinoma, LRIG1 levels were significantly elevated compared to women with benign or borderline type tumors. High LRIG1 plasma levels were associated with worse overall survival and shorter disease-free survival both in the group of all malignant cases and among the stage 3 cases only. LRIG1 was an independent prognostic factor in patients with stage 3 ovarian carcinoma.

Conclusion: LRIG1 plasma levels were elevated in patients with ovarian carcinoma, and high levels were associated with poor prognosis, suggesting that LRIG1 might be an etiologic factor and a potentially useful biomarker in ovarian carcinoma.

Ort, förlag, år, upplaga, sidor
Taylor & Francis, 2022
Nyckelord
biomarker, LRIG1, Ovarian carcinoma, plasma, prognosis, Simoa
Nationell ämneskategori
Cancer och onkologi
Forskningsämne
onkologi
Identifikatorer
urn:nbn:se:umu:diva-201254 (URN)10.1080/0284186X.2022.2140016 (DOI)000878575500001 ()36326616 (PubMedID)2-s2.0-85141433333 (Scopus ID)
Forskningsfinansiär
Cancerfonden, 2018/546Cancerfonden, 2018/384Umeå universitetVästerbottens läns landsting, RV 836951Cancerforskningsfonden i Norrland, AMP 21-1047
Tillgänglig från: 2022-11-25 Skapad: 2022-11-25 Senast uppdaterad: 2022-12-30Bibliografiskt granskad
Herdenberg, C., Mutie, P., Billing, O., Abdullah, A., Strawbridge, R. J., Dahlman, I., . . . Hedman, H. (2021). LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes. Communications Biology, 4(1), Article ID 90.
Öppna denna publikation i ny flik eller fönster >>LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes
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2021 (Engelska)Ingår i: Communications Biology, E-ISSN 2399-3642, Vol. 4, nr 1, artikel-id 90Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins have been implicated as regulators of growth factor signaling; however, the possible redundancy among mammalian LRIG1, LRIG2, and LRIG3 has hindered detailed elucidation of their physiological functions. Here, we show that Lrig-null mouse embryonic fibroblasts (MEFs) are deficient in adipogenesis and bone morphogenetic protein (BMP) signaling. In contrast, transforming growth factor-beta (TGF-beta) and receptor tyrosine kinase (RTK) signaling appeared unaltered in Lrig-null cells. The BMP signaling defect was rescued by ectopic expression of LRIG1 or LRIG3 but not by expression of LRIG2. Caenorhabditis elegans with mutant LRIG/sma-10 variants also exhibited a lipid storage defect. Human LRIG1 variants were strongly associated with increased body mass index (BMI) yet protected against type 2 diabetes; these effects were likely mediated by altered adipocyte morphology. These results demonstrate that LRIG proteins function as evolutionarily conserved regulators of lipid metabolism and BMP signaling and have implications for human disease. Herdenberg et al. show that adipogenesis and BMP signaling are altered in mouse cells deficient in LRIG (Leucine-rich repeats and immunoglobulin-like domains) proteins. They find that mutant LRIG/sma-10 variant worms exhibit lipid storage defects and that human LRIG1 variants are associated with higher body mass index, yet protect against type 2 diabetes. This study suggests an evolutionarily conserved role of LRIG proteins for lipid metabolism and BMP signaling.

Ort, förlag, år, upplaga, sidor
Springer Nature, 2021
Nationell ämneskategori
Cell- och molekylärbiologi
Identifikatorer
urn:nbn:se:umu:diva-180823 (URN)10.1038/s42003-020-01613-w (DOI)000613509200014 ()33469151 (PubMedID)2-s2.0-85099541477 (Scopus ID)
Tillgänglig från: 2021-02-26 Skapad: 2021-02-26 Senast uppdaterad: 2022-09-09Bibliografiskt granskad
De Vincenti, A. P., Alsina, F. C., Ferrero Restelli, F., Hedman, H., Ledda, F. & Paratcha, G. (2021). Lrig1 and Lrig3 cooperate to control Ret receptor signaling, sensory axonal growth and epidermal innervation. Development, 148(16), Article ID dev197020.
Öppna denna publikation i ny flik eller fönster >>Lrig1 and Lrig3 cooperate to control Ret receptor signaling, sensory axonal growth and epidermal innervation
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2021 (Engelska)Ingår i: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 148, nr 16, artikel-id dev197020Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Negative feedback loops represent a regulatory mechanism that guarantees that signaling thresholds are compatible with a physiological response. Previously, we established that Lrig1 acts through this mechanism to inhibit Ret activity. However, it is unclear whether other Lrig family members play similar roles. Here, we show that Lrig1 and Lrig3 are co-expressed in Ret-positive mouse dorsal root ganglion (DRG) neurons. Lrig3, like Lrig1, interacts with Ret and inhibits GDNF/Ret signaling. Treatment of DRG neurons with GDNF ligands induces a significant increase in the expression of Lrig1 and Lrig3. Our findings show that, whereas a single deletion of either Lrig1 or Lrig3 fails to promote Ret-mediated axonal growth, haploinsufficiency of Lrig1 in Lrig3 mutants significantly potentiates Ret signaling and axonal growth of DRG neurons in response to GDNF ligands. We observe that Lrig1 and Lrig3 act redundantly to ensure proper cutaneous innervation of nonpeptidergic axons and behavioral sensitivity to cold, which correlates with a significant increase in the expression of the cold-responsive channel TrpA1. Together, our findings provide insights into the in vivo functions through which Lrig genes control morphology, connectivity and function in sensory neurons.

Ort, förlag, år, upplaga, sidor
The Dompany of Biologists, 2021
Nyckelord
Cutaneous sensory innervation and nociceptive neurons, Dorsal root ganglia (DRG), GDNF, GFRα, Lrig family members, Mouse, Ret
Nationell ämneskategori
Cancer och onkologi
Identifikatorer
urn:nbn:se:umu:diva-187480 (URN)10.1242/dev.197020 (DOI)000691627500007 ()34338291 (PubMedID)2-s2.0-85114200159 (Scopus ID)
Tillgänglig från: 2021-09-13 Skapad: 2021-09-13 Senast uppdaterad: 2022-09-09Bibliografiskt granskad
Billing, O., Holmgren, Y., Nosek, D., Hedman, H. & Hemmingsson, O. (2021). LRIG1 is a conserved EGFR regulator involved in melanoma development, survival and treatment resistance. Oncogene, 40, 3707-3718
Öppna denna publikation i ny flik eller fönster >>LRIG1 is a conserved EGFR regulator involved in melanoma development, survival and treatment resistance
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2021 (Engelska)Ingår i: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 40, s. 3707-3718Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a pan-negative regulator of receptor tyrosine kinase (RTK) signaling and a tumor suppressor in several cancers, but its involvement in melanoma is largely unexplored. Here, we aim to determine the role of LRIG1 in melanoma tumorigenesis, RTK signaling, and BRAF inhibitor resistance. We find that LRIG1 is downregulated during early tumorigenesis and that LRIG1 affects activation of the epidermal growth factor receptor (EGFR) in melanoma cells. LRIG1-dependent regulation of EGFR signaling is evolutionary conserved to the roundworm C. elegans, where negative regulation of the EGFR-Ras-Raf pathway by sma-10/LRIG completely depends on presence of the receptor let-23/EGFR. In a cohort of metastatic melanoma patients, we observe an association between LRIG1 and survival in the triple wild-type subtype and in tumors with high EGFR expression. During in vitro development of BRAF inhibitor resistance, LRIG1 expression decreases; and mimics LRIG1 knockout cells for increased EGFR expression. Treating resistant cells with recombinant LRIG1 suppresses AKT activation and proliferation. Together, our results show that sma-10/LRIG is a conserved regulator of RTK signaling, add to our understanding of LRIG1 in melanoma and identifies recombinant LRIG1 as a potential therapeutic against BRAF inhibitor-resistant melanoma.

Ort, förlag, år, upplaga, sidor
Springer Nature, 2021
Nationell ämneskategori
Kirurgi Cancer och onkologi
Identifikatorer
urn:nbn:se:umu:diva-182828 (URN)10.1038/s41388-021-01808-3 (DOI)000647099200001 ()33947959 (PubMedID)2-s2.0-85105305447 (Scopus ID)
Tillgänglig från: 2021-05-06 Skapad: 2021-05-06 Senast uppdaterad: 2024-04-18Bibliografiskt granskad
Abdullah Nasir, A., Herdenberg, C. & Hedman, H. (2021). Netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling. Scientific Reports, 11(1), Article ID 8585.
Öppna denna publikation i ny flik eller fönster >>Netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling
2021 (Engelska)Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 11, nr 1, artikel-id 8585Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Netrin-1 is a secreted protein that is well known for its involvement in axonal guidance during embryonic development and as an enhancer of cancer cell metastasis. Despite extensive efforts, the molecular mechanisms behind many of the physiological functions of netrin-1 have remained elusive. Here, we show that netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling in various cellular systems, including a mutually inhibitory interaction with the BMP-promoting function of leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins. The BMP inhibitory function of netrin-1 in mouse embryonic fibroblasts was dependent on the netrin receptor neogenin, with the expression level regulated by both netrin-1 and LRIG proteins. Our results reveal a previously unrecognized function of netrin-1 that may help to explain several of the developmental, physiological, and cancer-promoting functions of netrins at the signal transduction level.

Ort, förlag, år, upplaga, sidor
Nature Publishing Group, 2021
Nationell ämneskategori
Cancer och onkologi Cell- och molekylärbiologi
Identifikatorer
urn:nbn:se:umu:diva-182911 (URN)10.1038/s41598-021-87949-7 (DOI)000644194200021 ()33883596 (PubMedID)2-s2.0-85104705931 (Scopus ID)
Tillgänglig från: 2021-05-28 Skapad: 2021-05-28 Senast uppdaterad: 2022-09-15Bibliografiskt granskad
Faraz, M., Tellström, A., Edwinsdotter Ardnor, C., Grankvist, K., Huminiecki, L., Tavelin, B., . . . Ljuslinder, I. (2020). LRIG1 gene copy number analysis by ddPCR and correlations to clinical factors in breast cancer. BMC Cancer, 20(1), Article ID 459.
Öppna denna publikation i ny flik eller fönster >>LRIG1 gene copy number analysis by ddPCR and correlations to clinical factors in breast cancer
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2020 (Engelska)Ingår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 20, nr 1, artikel-id 459Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) copy number alterations and unbalanced gene recombination events have been reported to occur in breast cancer. Importantly, LRIG1 loss was recently shown to predict early and late relapse in stage I-II breast cancer.

Methods: We developed droplet digital PCR (ddPCR) assays for the determination of relative LRIG1 copy numbers and used these assays to analyze LRIG1 in twelve healthy individuals, 34 breast tumor samples previously analyzed by fluorescence in situ hybridization (FISH), and 423 breast tumor cytosols.

Results: Four of the LRIG1/reference gene assays were found to be precise and robust, showing copy number ratios close to 1 (mean, 0.984; standard deviation, +/-0.031) among the healthy control population. The correlation between the ddPCR assays and previous FISH results was low, possibly because of the different normalization strategies used. One in 34 breast tumors (2.9%) showed an unbalanced LRIG1 recombination event. LRIG1 copy number ratios were associated with the breast cancer subtype, steroid receptor status, ERBB2 status, tumor grade, and nodal status. Both LRIG1 loss and gain were associated with unfavorable metastasis-free survival; however, they did not remain significant prognostic factors after adjustment for common risk factors in the Cox regression analysis. Furthermore, LRIG1 loss was not significantly associated with survival in stage I and II cases.

Conclusions: Although LRIG1 gene aberrations may be important determinants of breast cancer biology, and prognostic markers, the results of this study do not verify an important role for LRIG1 copy number analyses in predicting the risk of relapse in early-stage breast cancer.

Ort, förlag, år, upplaga, sidor
BioMed Central, 2020
Nyckelord
Breast cancer, LRIG1, Gene copy number, ddPCR, Prognosis
Nationell ämneskategori
Cancer och onkologi
Identifikatorer
urn:nbn:se:umu:diva-172514 (URN)10.1186/s12885-020-06919-w (DOI)000537685500004 ()32448168 (PubMedID)2-s2.0-85085414966 (Scopus ID)
Forskningsfinansiär
CancerfondenVästerbottens läns landsting
Tillgänglig från: 2020-07-01 Skapad: 2020-07-01 Senast uppdaterad: 2022-09-09Bibliografiskt granskad
Stefansson, K., Oda, H., Öfverman, C., Lundin, E., Hedman, H. & Lindquist, D. (2019). LRIG1‑2 and LMO7 immunoreactivity in vulvar squamous cell carcinoma: association with prognosis in relation to HPV‑DNA and p16INK4a status. Oncology Reports, 42(1), 142-150
Öppna denna publikation i ny flik eller fönster >>LRIG1‑2 and LMO7 immunoreactivity in vulvar squamous cell carcinoma: association with prognosis in relation to HPV‑DNA and p16INK4a status
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2019 (Engelska)Ingår i: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 42, nr 1, s. 142-150Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The present study was conducted to investigate the possible prognostic value of molecular markers LRIG1‑2 and LIM domain 7 protein (LMO7) in vulvar squamous cell carcinoma (VSCC) and their possible correlation to human papilloma virus (HPV)‑ and p16INK4a‑status of the tumors. Patients diagnosed with VSCC at the University Hospital of Umeå, Sweden, during the years 1990‑2013 were selected. Tumor blocks were retrieved from tissue archives and clinical data were collected from the records of patients. HPV‑PCR analysis, HPV genotyping and immunohistochemistry were performed. In total, 112 patients were included. Forty percent of the tumors were HPV‑positive, 27% were p16INK4a‑positive and 23% were positive for both HPV and p16INK4a (considered HPV‑driven). HPV‑positivity and p16INK4a‑positivity were associated with prolonged disease‑free survival (DFS) in Kaplan‑Meier survival analysis. Leucine‑rich repeats and immunoglobulin‑like domains 1 (LRIG1) immunoreactivity was not significantly associated with survival. High leucine‑rich repeats and immunoglobulin‑like domains 2 (LRIG2) immunoreactivity was associated with a prolonged overall survival (OS) (P=0.001). By analyzing HPV‑negative cases only, it was determined that high LRIG2 immunoreactivity was associated with both favorable OS (P=0.008) and DFS (P=0.031). LRIG2 immunoreactivity was also an independent prognostic factor in multivariate analysis of OS (P=0.002, HR=0.41; 95% CI, 0.24‑0.71). High immunoreactivity with LMO7‑1250 antibody was associated with survival benefits in the whole cohort (OS; P=0.011) although DFS was only prolonged in HPV‑negative and not HPV‑driven tumors (P=0.038 and 0.042, respectively). The present study indicated that LRIG2 and LMO7 may be useful prognostic markers in VSCC, particularly for patients without HPV‑driven tumors or with advanced tumors at diagnosis. In contrast to earlier observations regarding other types of squamous cell carcinoma, LRIG1 was not a significant prognostic factor in VSCC.

Ort, förlag, år, upplaga, sidor
Spandidos Publications, 2019
Nyckelord
vulvar squamous cell carcinoma, leucine‑rich repeats and immunoglobulin‑like domains, human papillomavirus, p16INK4a, survival
Nationell ämneskategori
Cancer och onkologi
Forskningsämne
hälso- och sjukvårdsforskning
Identifikatorer
urn:nbn:se:umu:diva-159681 (URN)10.3892/or.2019.7138 (DOI)000474808700012 ()31059071 (PubMedID)2-s2.0-85066789212 (Scopus ID)
Tillgänglig från: 2019-06-03 Skapad: 2019-06-03 Senast uppdaterad: 2023-10-04Bibliografiskt granskad
Organisationer
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0001-6891-6996

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