Umeå University's logo

umu.sePublications
Change search
Link to record
Permanent link

Direct link
Publications (10 of 41) Show all publications
Wilms, T., Boldrup, L., Gu, X., Coates, P. J., Sgaramella, N. & Nylander, K. (2021). High Levels of Low-Density Lipoproteins Correlate with Improved Survival in Patients with Squamous Cell Carcinoma of the Head and Neck. Biomedicines, 9(5), Article ID 506.
Open this publication in new window or tab >>High Levels of Low-Density Lipoproteins Correlate with Improved Survival in Patients with Squamous Cell Carcinoma of the Head and Neck
Show others...
2021 (English)In: Biomedicines, E-ISSN 2227-9059, Vol. 9, no 5, article id 506Article in journal (Refereed) Published
Abstract [en]

Circulating lipoproteins as risk factors or prognostic indicators for various cancers have been investigated previously; however, no clear consensus has been reached. In this study, we aimed at evaluating the impact of serum lipoproteins on the prognosis of patients with squamous cell carcinoma of the head and neck (SCCHN). Levels of total cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides and lipoprotein(a) were measured in serum samples from 106 patients and 28 healthy controls. We found that HDL was the only lipoprotein exhibiting a significant difference in concentration between healthy controls and patients (p = 0.012). Kaplan–Meier survival curves indicated that patients with high levels of total cholesterol or LDL had better overall survival than patients with normal levels (p = 0.028 and p = 0.007, respectively). Looking at patients without lipid medication (n = 89) and adjusting for the effects of TNM stage and weight change, multivariate Cox regression models indicated that LDL was an independent prognostic factor for both overall (p = 0.005) and disease-free survival (p = 0.013). In summary, our study revealed that high LDL level is beneficial for survival outcome in patients with SCCHN. Use of cholesterol-lowering medicines for prevention or management of SCCHN needs to be evaluated carefully.

Place, publisher, year, edition, pages
MDPI, 2021
Keywords
lipoprotein, SCCHN, prognosis
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-182833 (URN)10.3390/biomedicines9050506 (DOI)000653486500001 ()2-s2.0-85105631173 (Scopus ID)
Funder
Swedish Cancer Society, 20 0754 PjF 01HRegion Västerbotten
Available from: 2021-05-06 Created: 2021-05-06 Last updated: 2022-09-15Bibliographically approved
Boldrup, L., Coates, P., Gu, X., Wang, L., Fåhraeus, R., Wilms, T., . . . Nylander, K. (2021). Low potential of circulating interleukin 1 receptor antagonist as a prediction marker for squamous cell carcinoma of the head and neck. Journal of Oral Pathology & Medicine, 50(8), 785-794
Open this publication in new window or tab >>Low potential of circulating interleukin 1 receptor antagonist as a prediction marker for squamous cell carcinoma of the head and neck
Show others...
2021 (English)In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 50, no 8, p. 785-794Article in journal (Refereed) Published
Abstract [en]

Background: Circulating markers are attractive molecules for prognosis and management of cancer that allow sequential monitoring of patients during and after treatment. Based on previous protein profiling data, circulating interleukin 1 receptor antagonist (IL-1Ra) was evaluated as a potential diagnostic and prognostic marker for squamous cell carcinomas of the head and neck (SCCHN). In this study, we aimed at confirming the clinical relevance of plasma IL-1Ra in SCCHN and exploring its potential as a prediction marker for SCCHN.

Methods: Plasma from 87 patients with SCCHN, control plasma from 28 healthy individuals and pre-diagnostic plasma from 44 patients with squamous cell carcinoma of the oral tongue (SCCOT) and 88 matched controls were analysed with IL-1Ra electrochemiluminescence immunoassays from mesoscale diagnostics.

Results: Plasma IL-1Ra was found to be up-regulated in patients with oral tongue, gingiva and base of tongue tumours compared to healthy individuals (p < 0.01). IL-1Ra levels positively correlated with tumour size (p < 0.01) and body mass index (p = 0.013). Comparing pre-diagnostic plasma to the matched controls, similar IL1-Ra levels were seen (p = 0.05).

Conclusion: The anti-inflammatory cytokine IL-1Ra could be a diagnostic marker for SCCHN, whereas its potential as a cancer prediction marker was not supported by our data.

Place, publisher, year, edition, pages
John Wiley & Sons, 2021
Keywords
IL-1Ra, plasma, squamous cell carcinoma
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-183579 (URN)10.1111/jop.13187 (DOI)000648481300001 ()33880804 (PubMedID)2-s2.0-85105414094 (Scopus ID)
Funder
Cancerforskningsfonden i NorrlandSwedish Cancer Society, 20 0754 PjF 01HRegion VästerbottenSwedish Research Council, VR 2017-00650
Available from: 2021-06-01 Created: 2021-06-01 Last updated: 2021-12-30Bibliographically approved
Salehi, A. M., Norberg-Spaak, L., Wilms, T., Vallin, S., Boldrup, L., Sgaramella, N., . . . Nylander, K. (2020). Comparison of Quality of Life among Patients with Oro-Hypopharyngeal Cancer after Tonsillectomy and Panscopy Using Transoral Robotic Surgery: A Pilot Study. Case Reports in Oncology, 13(3), 1295-1303
Open this publication in new window or tab >>Comparison of Quality of Life among Patients with Oro-Hypopharyngeal Cancer after Tonsillectomy and Panscopy Using Transoral Robotic Surgery: A Pilot Study
Show others...
2020 (English)In: Case Reports in Oncology, E-ISSN 1662-6575, Vol. 13, no 3, p. 1295-1303Article in journal (Refereed) Published
Abstract [en]

Studies have shown lower treatment-related morbidity when using transoral robotic surgery (TORS) compared to conventional surgery. Patients investigated for oro- and hypopharyngeal cancer (T1, T2) were compared concerning quality of life (QoL) after tonsillectomy and TORS using validated QoL questionnaires: QLQ-C30 and QLQ-H&N35. The patients treated with TORS showed a higher pain score and thus also a higher need for painkillers, whereas they had lower values on self-assessment of anxiety/depression using the Hospital Anxiety and Depression Scale score. The pre- and postoperative information given did not meet the expectations of the patients treated with conventional surgery. The present data show advantages of the TORS technique from the patients' perspective. Even if patients treated with TORS are in need of more painkilling treatment, they cope better with the long-term effects of treatment, as judged by self-assessment of anxiety and depression.

Place, publisher, year, edition, pages
S. Karger, 2020
Keywords
Quality of life, Transoral robotic surgery, Oro-hypopharyngeal cancer, QLQ-C30, H&N35
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-179578 (URN)10.1159/000509743 (DOI)000605366900037 ()33250745 (PubMedID)2-s2.0-85094674366 (Scopus ID)
Funder
Swedish Cancer Society, 18 05 42
Available from: 2021-02-04 Created: 2021-02-04 Last updated: 2023-11-17Bibliographically approved
Attaran, N., Gu, X., Coates, P. J., Fåhraeus, R., Boldrup, L., Wilms, T., . . . Nylander, K. (2020). Downregulation of TAP1 in Tumor-Free Tongue Contralateral to Squamous Cell Carcinoma of the Oral Tongue, an Indicator of Better Survival.. International Journal of Molecular Sciences, 21(17), Article ID E6220.
Open this publication in new window or tab >>Downregulation of TAP1 in Tumor-Free Tongue Contralateral to Squamous Cell Carcinoma of the Oral Tongue, an Indicator of Better Survival.
Show others...
2020 (English)In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 21, no 17, article id E6220Article in journal (Refereed) Published
Abstract [en]

Oral cancers are surrounded by epithelium that histologically might seem normal, but genetically has aberrations. In patients with squamous cell carcinoma of the oral tongue (SCCOT), it is therefore important to study not only the tumor but also the clinically tumor-free contralateral tongue tissue that remains in the patient after treatment to map changes of prognostic and/or diagnostic value. The transporter associated with antigen processing (TAP) dimer is a key factor in the process of activating cytotoxic T cells. By downregulating the expression of TAP, tumor cells can escape cytotoxic T cell recognition. Biopsies from tumor and clinically tumor-free contralateral tongue tissue in 21 patients with SCCOT were analyzed together with tongue biopsies from 14 healthy individuals, which served as the control group. Dividing patients into TAP1-high and TAP1-low groups according to the median TAP1 level in tumor-free samples showed that patients with lower TAP1 mRNA levels in tumor-free samples had better overall (p = 0.003) and disease-free survival (p = 0.002). The results showing that TAP1 levels in tumor-free tongue tissue contralateral to the SCCOT correlate with survival is an important contribution to early diagnosis and follow up of SCCOT.

Place, publisher, year, edition, pages
MDPI, 2020
Keywords
MHC I, SCCOT, TAP1, field cancerization
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-174915 (URN)10.3390/ijms21176220 (DOI)000570369800001 ()32867395 (PubMedID)2-s2.0-85090050694 (Scopus ID)
Available from: 2020-09-10 Created: 2020-09-10 Last updated: 2023-03-23Bibliographically approved
Brychtova, V., Coates, P. J., Hrabal, V., Boldrup, L., Fabian, P., Vojtesek, B., . . . Nylander, K. (2020). Keratin 36, a specific marker of tongue filiform papillae, is downregulated in squamous cell carcinoma of the mobile tongue. Molecular and clinical oncology, 12(5), 421-428
Open this publication in new window or tab >>Keratin 36, a specific marker of tongue filiform papillae, is downregulated in squamous cell carcinoma of the mobile tongue
Show others...
2020 (English)In: Molecular and clinical oncology, ISSN 2049-9450, E-ISSN 2049-9469, Vol. 12, no 5, p. 421-428Article in journal (Refereed) Published
Abstract [en]

Human keratin 36 (K36) is a member of the hair keratin family and is a marker of hair cortex differentiation. The human KRT36 gene is located on the long arm of chromosome 17 and belongs to the cluster of structurally unrelated acidic hair keratins. Recently, it has been reported that KRT36 mRNA is specifically expressed in normal tongue epithelium and downregulated in squamous cell carcinomas of the mobile tongue. Furthermore, KRT36 levels have been reported to be downregulated in clinically normal mobile tongue tissue that is adjacent to tumours, suggesting it could be a marker of pre-neoplastic changes. However, the exact role and the potential role of K36 in tongue tumour formation remains unclear. The aim of the present study was to investigate expression of K36 in a series of squamous cell carcinomas of the mobile tongue, normal mobile tongue and a small panel of other human tissues (normal tissue from the appendix, cervix, hair, lip, mamilla, nail, oesophagus, skin, thymus and vagina) and selected cancer tissue (cervical cancer, melanoma and basal cell carcinoma). Affinity purified polyclonal antibodies against K36 were generated and used for immunohistochemical analysis. The results revealed that in the normal tongue, K36 was detected specifically in the filiform papillae of the dorsal surface of the tongue. Additionally, none of the tongue cancer tissue samples were K36-positive. Immunostaining also revealed that K36 was expressed in nail beds, Hassal's corpuscles in the thymus and the hair cortex. However, K36 was not expressed in the squamous epithelia of the skin, cervix and oesophagus, and the squamous cells of cervical carcinomas, basal cell carcinoma or melanoma. The present data indicated that K36 may be inactivated in tumours of the tongue. However, whether this is part of the tumoural process or if it is an effect of the tumour itself remains to be elucidated.

Place, publisher, year, edition, pages
Spandidos Publications, 2020
Keywords
keratin 36, mobile tongue, squamous cell carcinoma, thymus, nail
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-170392 (URN)10.3892/mco.2020.2005 (DOI)000523727900005 ()32257198 (PubMedID)2-s2.0-85085290557 (Scopus ID)
Available from: 2020-05-06 Created: 2020-05-06 Last updated: 2023-03-23Bibliographically approved
Boldrup, L., Coates, P., Gu, X., Wang, L., Fåhraeus, R., Wilms, T., . . . Nylander, K. (2020). Levels of MUC1 in tumours and serum of patients with different sub-types of squamous cell carcinoma of the head and neck. Oncology Letters, 20(2), 1709-1718
Open this publication in new window or tab >>Levels of MUC1 in tumours and serum of patients with different sub-types of squamous cell carcinoma of the head and neck
Show others...
2020 (English)In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 20, no 2, p. 1709-1718Article in journal (Refereed) Published
Abstract [en]

Mucin 1 (MUC1) is a membrane-bound and secreted glycoprotein that has a protective role in surface epithelia. We recently demonstrated that MUC1 mRNA expression was upregulated in tumour-free tongue tissues adjacent to squamous cell carcinoma of the oral tongue (SCCOT) compared with that in the tumour tissues. The present study investigated MUC1 protein in SCCOT tissue and serum from patients with squamous cell carcinoma of the head and neck (SCCHN) at different sub-sites. The results from immunohistochemistry demonstrated that all SCCOT tissues expressed MUC1; however, the protein levels were not correlated with MUC1 mRNA levels in the same tumours. Furthermore, serum MUC1 level was lower in patients with SCCOT, tonsil SCC and gingival SCC compared with that in healthy subjects; however, the difference was only significant for patients with SCCOT (P=0.0421). No correlation was seen between MUC1 level in tumour tissues and MUCI level in serum from the same patients. The absence of correlation between MUC1 protein and mRNA levels in SCCOT tissues emphasized the importance of validating genomic data in clinical samples. Although significant MUC1 downregulation was observed in the serum of patients with SCCOT, there was a large variation within the groups, suggesting that MUC1 may not be used as a biomarker for these types of tumors.

Place, publisher, year, edition, pages
Spandidos Publications, 2020
Keywords
mucin 1, squamous cell carcinomas of the oral tongue, blood markers, prognosis, microarray, validation
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-174865 (URN)10.3892/ol.2020.11746 (DOI)000563832100076 ()32724413 (PubMedID)2-s2.0-85087204210 (Scopus ID)
Available from: 2020-09-18 Created: 2020-09-18 Last updated: 2023-03-23Bibliographically approved
Wilms, T., Gu, X., Boldrup, L., Coates, P. J., Fåhraeus, R., Wang, L., . . . Nylander, K. (2020). PD-L1 in squamous cell carcinoma of the oral tongue shows gender-specific association with prognosis. Oral Diseases, 26(7), 1414-1423
Open this publication in new window or tab >>PD-L1 in squamous cell carcinoma of the oral tongue shows gender-specific association with prognosis
Show others...
2020 (English)In: Oral Diseases, ISSN 1354-523X, E-ISSN 1601-0825, Vol. 26, no 7, p. 1414-1423Article in journal (Refereed) Published
Abstract [en]

Objective: To use alternative quantitation approaches to clarify the clinical implication of programmed cell death ligand 1 (PD‐L1) in squamous cell carcinoma of the oral tongue (SCCOT).

Materials and Methods: Ventana SP263 immunohistochemistry assay and a multiplicative QuickScore method were applied to quantify PD‐L1 in tumor and surrounding immune cells from 101 patients with SCCOT. Tumor‐infiltrating immune cells were estimated from bulk tissue transcriptional profiles of 25 patients. Circulating PD‐L1 levels were measured in serum from 30 patients using an electrochemiluminescence assay platform.

Results: We found higher tumor cell PD‐L1 levels in females than males ( = .019). For patients with low PD‐L1 in tumor cells, better survival was seen in males than females (overall survival  = .021, disease‐free survival  = .020). Tumor‐infiltrating natural killer T cells, immature dendritic cells, and M1 macrophages were positively associated with tumor cell PD‐L1 ( < .05).

Conclusions: Our data confirmed the significance of gender on tumor cell PD‐L1 expression and demonstrated combined effects of gender and PD‐L1 levels on clinical outcome in patients with SCCOT. The data also indicated the involvement of specific immune cell types in PD‐L1‐regulated immune evasion.

Place, publisher, year, edition, pages
John Wiley & Sons, 2020
Keywords
gender, PD-L1, SCCOT
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-173674 (URN)10.1111/odi.13414 (DOI)000545475200001 ()32406589 (PubMedID)2-s2.0-85087561132 (Scopus ID)
Funder
Swedish Cancer Society, 18 0542Region Västerbotten
Available from: 2020-07-23 Created: 2020-07-23 Last updated: 2021-05-07Bibliographically approved
Gu, X., Wang, L., Coates, P. J., Boldrup, L., Fåhraeus, R., Wilms, T., . . . Nylander, K. (2020). Transfer-RNA-Derived Fragments Are Potential Prognostic Factors in Patients with Squamous Cell Carcinoma of the Head and Neck. Genes, 11(11), Article ID 1344.
Open this publication in new window or tab >>Transfer-RNA-Derived Fragments Are Potential Prognostic Factors in Patients with Squamous Cell Carcinoma of the Head and Neck
Show others...
2020 (English)In: Genes, E-ISSN 2073-4425, Vol. 11, no 11, article id 1344Article in journal (Refereed) Published
Abstract [en]

Transfer-RNA-derived fragments (tRFs) are a class of small non-coding RNAs that are functionally different from their parental transfer RNAs (tRNAs). tRFs can regulate gene expression by several mechanisms, and are involved in a variety of pathological processes. Here, we aimed at understanding the composition and abundance of tRFs in squamous cell carcinoma of the head and neck (SCCHN), and evaluated the potential of tRFs as prognostic markers in this cancer type. We obtained tRF expression data from The Cancer Genome Atlas (TCGA) HNSC cohort (523 patients) using MINTbase v2.0, and correlated to available TCGA clinical data. RNA-binding proteins were predicted according to the calculated Position Weight Matrix (PWM) score from the RNA-Binding Protein DataBase (RBPDB). A total of 10,158 tRFs were retrieved and a high diversity in expression levels was seen. Fifteen tRFs were found to be significantly associated with overall survival (Kaplan-Meier survival analysis, log rank test p-value < 0.01). The top prognostic marker, tRF-20-S998LO9D (p < 0.001), was further measured in tumor and tumor-free samples from 16 patients with squamous cell carcinoma of the oral tongue and 12 healthy controls, and was significantly upregulated in tumor compared to matched tumor-free tongue (p < 0.001). Results suggest that tRFs are useful prognostic markers in SCCHN

Place, publisher, year, edition, pages
MDPI, 2020
Keywords
tRNA-derived fragment, SCCHN, prognostic marker
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-177782 (URN)10.3390/genes11111344 (DOI)000593183600001 ()33202812 (PubMedID)2-s2.0-85096060293 (Scopus ID)
Funder
Swedish Cancer Society, 18 0542
Available from: 2020-12-22 Created: 2020-12-22 Last updated: 2024-07-04Bibliographically approved
Alhouayek, M., Boldrup, L. & Fowler, C. J. (2019). Altered mRNA Expression of Genes Involved in Endocannabinoid Signalling in Squamous Cell Carcinoma of the Oral Tongue. Cancer Investigation, 37(8), 327-338
Open this publication in new window or tab >>Altered mRNA Expression of Genes Involved in Endocannabinoid Signalling in Squamous Cell Carcinoma of the Oral Tongue
2019 (English)In: Cancer Investigation, ISSN 0735-7907, E-ISSN 1532-4192, Vol. 37, no 8, p. 327-338Article in journal (Refereed) Published
Abstract [en]

Little is known about the endocannabinoid (eCB) system in squamous cell carcinoma of the oral tongue (SCCOT). Here we have investigated, at the mRNA level, expression of genes coding for the components of the eCB system in tumour and non-malignant samples from SCCOT patients. Expression of NAPEPLD and PLA2G4E, coding for eCB anabolic enzymes, was higher in the tumour tissue than in non-malignant tissue. Among genes coding for eCB catabolic enzymes, expression of MGLL was lower in tumour tissue while PTGS2 was increased. It is concluded that the eCB system may be dysfunctional in SCCOT.

Keywords
Squamous cell carcinoma of the oral tongue, endocannabinoids, cyclooxygenase-2, N-acyl- osphatidylethanolamine phospholipase D, monoacylglycerol lipase
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-163070 (URN)10.1080/07357907.2019.1638394 (DOI)000482287600001 ()31423851 (PubMedID)2-s2.0-85070985631 (Scopus ID)
Available from: 2019-11-27 Created: 2019-11-27 Last updated: 2023-03-24Bibliographically approved
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
Show others...
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)2-s2.0-85064436863 (Scopus ID)
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: 2023-03-23Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-1399-592x

Search in DiVA

Show all publications