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Boldrup, Linda
Publications (10 of 31) Show all publications
Gu, X., Wang, L., Boldrup, L., Coates, P. J., Fåhraeus, R., Sgaramella, N., . . . Nylander, K. (2019). AP001056.1, A Prognosis-Related Enhancer RNA in Squamous Cell Carcinoma of the Head and Neck. Cancers, 11(3), Article ID 347.
Open this publication in new window or tab >>AP001056.1, A Prognosis-Related Enhancer RNA in Squamous Cell Carcinoma of the Head and Neck
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2019 (English)In: Cancers, ISSN 2072-6694, Vol. 11, no 3, article id 347Article in journal (Refereed) Published
Abstract [en]

A growing number of long non-coding RNAs (lncRNAs) have been linked to squamous cell carcinoma of the head and neck (SCCHN). A subclass of lncRNAs, termed enhancer RNAs (eRNAs), are derived from enhancer regions and could contribute to enhancer function. In this study, we developed an integrated data analysis approach to identify key eRNAs in SCCHN. Tissue-specific enhancer-derived RNAs and their regulated genes previously predicted using the computational pipeline PreSTIGE, were considered as putative eRNA-target pairs. The interactive web servers, TANRIC (the Atlas of Noncoding RNAs in Cancer) and cBioPortal, were used to explore the RNA levels and clinical data from the Cancer Genome Atlas (TCGA) project. Requiring that key eRNAs should show significant associations with overall survival (Kaplan-Meier log-rank test, p < 0.05) and the predicted target (correlation coefficient r > 0.4, p < 0.001), we identified five key eRNA candidates. The most significant survival-associated eRNA was AP001056.1 with ICOSLG encoding an immune checkpoint protein as its regulated target. Another 1640 genes also showed significant correlation with AP001056.1 (r > 0.4, p < 0.001), with the "immune system process" being the most significantly enriched biological process (adjusted p < 0.001). Our results suggest that AP001056.1 is a key immune-related eRNA in SCCHN with a positive impact on clinical outcome.

Place, publisher, year, edition, pages
MDPI, 2019
Keywords
AP001056.1, lncRNA, enhancer, SCCHN, ICOSLG, tumor immunity
National Category
Cell and Molecular Biology Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-159881 (URN)10.3390/cancers11030347 (DOI)000468550200077 ()30862109 (PubMedID)
Funder
Swedish Cancer Society, 18 05 42Swedish Cancer Society, 18 02 96Västerbotten County Council
Available from: 2019-06-10 Created: 2019-06-10 Last updated: 2019-06-10Bibliographically approved
Gu, X., Coates, P. J., Boldrup, L., Wang, L., Krejci, A., Hupp, T., . . . Nylander, K. (2019). Copy number variation: A prognostic marker for young patients with squamous cell carcinoma of the oral tongue. Journal of Oral Pathology & Medicine, 48(1), 24-30
Open this publication in new window or tab >>Copy number variation: A prognostic marker for young patients with squamous cell carcinoma of the oral tongue
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2019 (English)In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 48, no 1, p. 24-30Article in journal (Refereed) Published
Abstract [en]

Background The incidence of squamous cell carcinoma of the oral tongue (SCCOT) is increasing in people under age 40. There is an urgent need to identify prognostic markers that help identify young SCCOT patients with poor prognosis in order to select these for individualized treatment. Materials and methods To identify genetic markers that can serve as prognostic markers for young SCCOT patients, we first investigated four young (<= 40 years) and five elderly patients (>= 50 years) using global RNA sequencing and whole-exome sequencing. Next, we combined our data with data on SCCOT from the cancer genome atlas (TCGA), giving a total of 16 young and 104 elderly, to explore the correlations between genomic variations and clinical outcomes. Results In agreement with previous studies, we found that SCCOT from young and elderly patients was transcriptomically and also genomically similar with no significant differences regarding cancer driver genes, germline predisposition genes, or the burden of somatic single nucleotide variations (SNVs). However, a disparate copy number variation (CNV) was found in young patients with distinct clinical outcome. Combined with data from TCGA, we found that the overall survival was significantly better in young patients with low-CNV (n = 5) compared to high-CNV (n = 11) burden (P = 0.044). Conclusions Copy number variation burden is a useful single prognostic marker for SCCOT from young, but not elderly, patients. CNV burden thus holds promise to form an important contribution when selecting suitable treatment protocols for young patients with SCCOT.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
age, copy number variation, prognosis, squamous cell carcinoma of the oral tongue, whole-exome sequencing
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-155648 (URN)10.1111/jop.12792 (DOI)000454799800005 ()30357923 (PubMedID)
Funder
Swedish Cancer Society, 17 0663Västerbotten County Council
Available from: 2019-01-25 Created: 2019-01-25 Last updated: 2019-01-25Bibliographically approved
Sgaramella, N., Wilms, T., Boldrup, L., Loljung, L., Gu, X., Coates, P. J., . . . Nylander, K. (2018). Ethnicity based variation in expression of E-cadherin in patients with squamous cell carcinoma of the oral tongue. Oncology Letters, 16(5), 6603-6607
Open this publication in new window or tab >>Ethnicity based variation in expression of E-cadherin in patients with squamous cell carcinoma of the oral tongue
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2018 (English)In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 16, no 5, p. 6603-6607Article in journal (Refereed) Published
Abstract [en]

The oral tongue is the most common site for tumours within the oral cavity. Despite intense research, there has been no improvement in the survival rate for patients with oral tongue squamous cell carcinoma (OTSCC) during the last decades. Differences between oral cancer patients based on ethno-geographical distribution have been reported. The present study used immunohistochemistry to evaluate commonly used markers of cancer cell phenotypes, E-cadherin, -catenin and cytokeratins 5 and 19, in 120 patients with OTSCC. To evaluate the impact of ethnicity, patients from Sweden and Italy were included. A higher proportion of Swedish patients exhibited high expression of E-cadherin in their tumours (P=0.039), and high levels of E-cadherin in Swedish OTSCC patients that had succumbed to their disease were associated with poor prognosis. These data demonstrated differences in the pathological characteristics of OTSCC between two different European populations. The findings emphasise the need to take ethnicity/geographical location of patients into account when comparing results from different studies of OTSCC.

Place, publisher, year, edition, pages
Spandidos Publications, 2018
Keywords
E-cadherin, beta catenin, squamous cell carcinoma, oral tongue, ethnicity
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-153550 (URN)10.3892/ol.2018.9452 (DOI)000448433500141 ()30405799 (PubMedID)
Funder
Swedish Cancer Society, 17 06 63Västerbotten County Council, MEYS-NPSI-LO1413
Available from: 2018-11-22 Created: 2018-11-22 Last updated: 2019-05-10Bibliographically approved
Sgaramella, N., Gu, X., Boldrup, L., Coates, P. J., Fåhraeus, R., Califano, L., . . . Nylander, K. (2018). Searching for new targets and treatments in the battle against squamous cell carcinoma of the head and neck, with specific focus on tumours of the tongue. Current Topics in Medicinal Chemistry, 18(3), 214-218
Open this publication in new window or tab >>Searching for new targets and treatments in the battle against squamous cell carcinoma of the head and neck, with specific focus on tumours of the tongue
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2018 (English)In: Current Topics in Medicinal Chemistry, ISSN 1568-0266, E-ISSN 1873-4294, Vol. 18, no 3, p. 214-218Article, review/survey (Refereed) Published
Abstract [en]

Squamous cell carcinoma of the head and neck, SCCHN, is a heterogeneous group of tumours not only concerning the site of origin but also regarding aetiology. The 5-year survival for the whole group of SCCHN tumours has not significantly improved over the last 20-25 years. Apart from tumour spread to lymph nodes, N status, gains and losses of specific chromosomes are the only factors shown to be independent prognostic markers for these tumours. Worldwide, an increasing number of people ≤ 40 years are seen being affected by tongue SCC, the most common tumour within the SCCHN group. Even without any clinical signs of metastasis, up to 30% of all tongue SCC have histologically detectable spread to lymph nodes. In this mini review, field cancerization, tumour microenvironment, the so called EMT (epithelial mesenchymal transition) process and the role of viruses in development of SCCHN are discussed as well as potential new therapeutic targets. For the group of tongue SCC, with the increasing incidence seen in young patients and particularly women, new data with impact on prognosis and treatment are urgently needed. But as long as data from the analyses of several sub sites are presented as valid for the whole group of tumours, this vital point is missed.

Place, publisher, year, edition, pages
Bentham Science Publishers, 2018
Keywords
squamous cell carcinoma, tongue, prognosis, therapy, miRNA, HPV, EBV, p63
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-148841 (URN)10.2174/1568026618666180116121624 (DOI)000432250800006 ()29345578 (PubMedID)
Available from: 2018-06-12 Created: 2018-06-12 Last updated: 2019-05-10Bibliographically approved
Boldrup, L., Troiano, G., Gu, X., Coates, P., Fåhraeus, R., Wilms, T., . . . Nylander, K. (2017). Evidence that circulating proteins are more promising than miRNAs for identification of patients with squamous cell carcinoma of the tongue. OncoTarget, 8(61), 103437-103448
Open this publication in new window or tab >>Evidence that circulating proteins are more promising than miRNAs for identification of patients with squamous cell carcinoma of the tongue
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2017 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 61, p. 103437-103448Article in journal (Refereed) Published
Abstract [en]

Despite intense research, squamous cell carcinoma of the tongue remains a devastating disease with a five-year survival of around 60%. Late detection and recurrence are the main causes for poor survival. The identification of circulating factors for early diagnosis and/or prognosis of cancer is a rapidly evolving field of interest, with the hope of finding stable and reliable markers of clinical significance. The aim of this study was to evaluate circulating miRNAs and proteins as potential factors for distinguishing patients with tongue squamous cell carcinoma from healthy controls. Array-based profiling of 372 miRNAs in plasma samples showed broad variations between different patients and did not show any evidence for their use in diagnosis of tongue cancer. Although one miRNA, miR-150, was significantly down-regulated in plasma from patients compared to controls. Surprisingly, the corresponding tumor tissue showed an up-regulation of miR-150. Among circulating proteins, 23 were identified as potential markers of squamous cell carcinoma of the tongue. These findings imply that circulating proteins are a more promising source of biomarkers for tongue squamous cell carcinomas than circulating miRNAs. The data also highlight that circulating markers are not always directly associated with tumor cell properties.

Place, publisher, year, edition, pages
IMPACT JOURNALS LLC, 2017
Keywords
miRNA, circulating markers, NT-3, miR-150, squamous cell carcinoma of the tongue
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-144977 (URN)10.18632/oncotarget.21402 (DOI)000419562500057 ()29262574 (PubMedID)
Available from: 2018-02-20 Created: 2018-02-20 Last updated: 2018-06-09Bibliographically approved
Troiano, G., Caponio, V. C., Boldrup, L., Gu, X., Lo Muzio, L., Sgaramella, N., . . . Nylander, K. (2017). Expression of the long non-coding RNA HOTAIR as a prognostic factor in squamous cell carcinoma of the head and neck: a systematic review and meta-analysis. OncoTarget, 8(42), 73029-73036
Open this publication in new window or tab >>Expression of the long non-coding RNA HOTAIR as a prognostic factor in squamous cell carcinoma of the head and neck: a systematic review and meta-analysis
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2017 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 42, p. 73029-73036Article, review/survey (Refereed) Published
Abstract [en]

Introduction: Long noncoding RNAs (lncRNAs) are often dysregulated in cancer tissue and seem to play an important role in neoplastic processes. Recent studies have shown that the HOX transcript antisense intergenic RNA (HOTAIR) may play a role as a marker of prognosis in squamous cell carcinoma of the head and neck (SCCHN). The aim of this study was to perform a meta-analysis of studies focused on the prognostic role of HOTAIR in SCCHN.

Results: At the end of the selection process, four studies were considered eligible for inclusion in the meta-analysis, comprising a total of 271 patients. Meta-analysis revealed that high expression of HOTAIR was associated with poor overall survival (HR, 1.90; 95% CI: [1.42, 2.53]; p < 0,0001), advanced tumor stage (OR, 3.44; 95% CI: [1.84, 6.43]; p < 0,001) and lymph-node metastasis (OR, 3.31; 95% CI: [1.24, 8.79]; p = 0,02).

Materials and Methods: The literature search was performed in the following databases: PUBMED, SCOPUS, EMBASE and Web of Science, in order to find studies that met the inclusion criteria.

Conclusions: Findings from this systematic review and meta-analysis revealed that HOTAIR represents a potential biomarker of prognosis in patients with squamous cell carcinoma of the head and neck.

Place, publisher, year, edition, pages
Impact Journals LLC, 2017
Keywords
lncRNA, lncRNAs, non-coding RNA, HOTAIR, biomarker
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-140648 (URN)10.18632/oncotarget.20373 (DOI)000411509400134 ()
Available from: 2017-10-18 Created: 2017-10-18 Last updated: 2019-05-10Bibliographically approved
Boldrup, L., Gu, X., Coates, P. J., Norberg-Spaak, L., Fåhraeus, R., Laurell, G., . . . Nylander, K. (2017). Gene expression changes in tumor free tongue tissue adjacent to tongue squamous cell carcinoma. OncoTarget, 8(12), 19389-19402
Open this publication in new window or tab >>Gene expression changes in tumor free tongue tissue adjacent to tongue squamous cell carcinoma
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2017 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 12, p. 19389-19402Article in journal (Refereed) Published
Abstract [en]

Due to the high frequency of loco-regional recurrences, which could be explained by changes in the field surrounding the tumor, patients with squamous cell carcinoma of head and neck show poor survival. Here we identified a total of 554 genes as dysregulated in clinically tumor free tongue tissue in patients with tongue tumors when compared to healthy control tongue tissue. Among the top dysregulated genes when comparing control and tumor free tissue were those involved in apoptosis (CIDEC, MUC1, ZBTB16, PRNP, ECT2), immune response (IFI27) and differentiation (KRT36). Data suggest that these are important findings which can aid in earlier diagnosis of tumor development, a relapse or a novel squamous cell carcinoma of the tongue, in the absence of histological signs of a tumor.

Keywords
tongue cancer, RNA expression, field cancerization
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-133220 (URN)10.18632/oncotarget.14288 (DOI)000396879200062 ()
Available from: 2017-04-12 Created: 2017-04-12 Last updated: 2018-06-09Bibliographically approved
Strindlund, K., Troiano, G., Sgaramella, N., Coates, P. J., Gu, X., Boldrup, L., . . . Nylander, K. (2017). Patients with high c-MYC-expressing squamous cell carcinomas of the tongue show better survival than those with low- and medium-expressing tumours. Journal of Oral Pathology & Medicine, 46(10), 967-971
Open this publication in new window or tab >>Patients with high c-MYC-expressing squamous cell carcinomas of the tongue show better survival than those with low- and medium-expressing tumours
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2017 (English)In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 46, no 10, p. 967-971Article in journal (Refereed) Published
Abstract [en]

Backgroundc-MYC is a potent oncoprotein with roles in a wide range of cellular processes such as differentiation, apoptosis and growth control. Deregulation of the MYC gene is commonly seen in human tumours resulting in overexpression of the protein. Here we studied expression of c-MYC in correlation to clinical outcome in patients with primary squamous cell carcinoma of the mobile tongue. MethodsImmunohistochemistry was used to identify c-MYC in a group of 104 tongue squamous cell carcinomas with an antibody directed against the N-terminal part of the protein. Staining was evaluated by multiplying the percentage of c-MYC-expressing cells with staining intensity, giving a quick score for each tumour. ResultsAll 104 tumours expressed c-MYC at varying levels. Quantitation according to per cent of positive cells and staining intensity revealed that most (15/21; 71%) high-expressing tumours were seen in males. Within the group of high c-MYC-expressing tumours, the majority were alive 2 and 5 years after treatment. ConclusionsThe present findings show that expression of c-MYC has prognostic value in squamous cell carcinoma of the tongue, and could be useful in choice of therapy.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
Keywords
c-MYC, radiotherapy, squamous cell carcinoma, tongue
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-141977 (URN)10.1111/jop.12579 (DOI)000414366000017 ()28393404 (PubMedID)
Available from: 2017-12-06 Created: 2017-12-06 Last updated: 2018-06-09Bibliographically approved
Troiano, G., Boldrup, L., Ardito, F., Gu, X., Lo Muzio, L. & Nylander, K. (2016). Circulating miRNAs from blood, plasma or serum as promising clinical biomarkers in oral squamous cell carcinoma: A systematic review of current findings. Oral Oncology, 63, 30-37
Open this publication in new window or tab >>Circulating miRNAs from blood, plasma or serum as promising clinical biomarkers in oral squamous cell carcinoma: A systematic review of current findings
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2016 (English)In: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 63, p. 30-37Article, review/survey (Refereed) Published
Abstract [en]

The purpose of this systematic review was to summarize current findings on the use of circulating miRNAs from blood, serum and plasma as cancer biomarkers in patients with oral squamous cell carcinoma. Studies were gathered after searching four different electronic databases: PUBMED, SCOPUS, Cochrane Library and Web of Science. Additional search was carried out through cross check on bibliography of selected articles. After the selection process made by two of the authors, 16 articles met the inclusion criteria and were included in the review. Results showed that circulating miRNAs from blood, serum or plasma represent promising candidates as cancer biomarkers in patients suffering from oral cancer. The possibility to predict recurrences and metastases through follow-up quantification of candidate miRNAs represents another potential feature to be addressed in future studies. However, methodological standardization and uniform sampling is needed to increase the power and accuracy of results. 

Keywords
MicroRNA, miRNAs, Micro RNA, miRNA, Oral cancer, Mouth cancers, Cancer biomarkers, Blood plasma, Blood serum, Tongue cancer
National Category
Clinical Laboratory Medicine Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-131661 (URN)10.1016/j.oraloncology.2016.11.001 (DOI)000392637300010 ()27938997 (PubMedID)
Available from: 2017-02-24 Created: 2017-02-24 Last updated: 2018-06-09Bibliographically approved
Gu, X., Boldrup, L., Coates, P. J., Fåhraeus, R., Nylander, E., Loizou, C., . . . Nylander, K. (2016). Epigenetic regulation of OAS2 shows disease-specific DNA methylation profiles at individual CpG sites. Scientific Reports, 6, Article ID 32579.
Open this publication in new window or tab >>Epigenetic regulation of OAS2 shows disease-specific DNA methylation profiles at individual CpG sites
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2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 32579Article in journal (Refereed) Published
Abstract [en]

Epigenetic modifications are essential regulators of biological processes. Decreased DNA methylation of OAS2 (2'-5'-Oligoadenylate Synthetase 2), encoding an antiviral protein, has been seen in psoriasis. To provide further insight into the epigenetic regulation of OAS2, we performed pyrosequencing to detect OAS2 DNA methylation status at 11 promoter and first exon located CpG sites in psoriasis (n = 12) and two common subtypes of squamous cell carcinoma (SCC) of the head and neck: tongue (n = 12) and tonsillar (n = 11). Compared to corresponding controls, a general hypomethylation was seen in psoriasis. In tongue and tonsillar SCC, hypomethylation was found at only two CpG sites, the same two sites that were least demethylated in psoriasis. Despite differences in the specific residues targeted for methylation/demethylation, OAS2 expression was upregulated in all conditions and correlations between methylation and expression were seen in psoriasis and tongue SCC. Distinctive methylation status at four successively located CpG sites within a genomic area of 63 bp reveals a delicately integrated epigenetic program and indicates that detailed analysis of individual CpGs provides additional information into the mechanisms of epigenetic regulation in specific disease states. Methylation analyses as clinical biomarkers need to be tailored according to disease-specific sites.

Keywords
Tympanic membrane, myringoplasty, perforation, Gelfoam®
National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-125822 (URN)10.1038/srep32579 (DOI)000391984400001 ()27572959 (PubMedID)
Available from: 2017-02-22 Created: 2017-02-22 Last updated: 2018-06-09Bibliographically approved
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