Combining factors on protein and gene level to predict radioresponse in head and neck cancer cell lines

Lovisa Farnebo (Corresponding Author), Fredrik Jerhammer, Rebecca Ceder, Roland Grafström, Linda Vainikka, Lena Thunell, Reidar Grénman, Ann-Charlotte Johansson, Karin Roberg

Research output: Contribution to journalArticleScientificpeer-review

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Abstract

Background: Radiotherapy is the main therapy for head and neck squamous cell carcinoma (HNSCC); however, treatment resistance and local recurrence are significant problems, highlighting the need for predictive markers. In this study, we evaluated selected proteins, mutations, and single nucleotide polymorphisms (SNPs) involved in apoptosis, cell proliferation, and DNA repair alone or combined as predictive markers for radioresponse in 42 HNSCC cell lines.

Methods: The expression of epidermal growth factor receptor, survivin, Bax, Bcl‐2, Bcl‐XL, cyclooxygenase‐2 (COX‐2), and heat shock protein 70 was analyzed by ELISA. Furthermore, mutations and SNPs in the p53 gene as well as SNPs in the MDM2, XRCC1, and XRCC3 genes were analyzed for their relation to radioresponse. To enable the evaluation of the predictive value of several factors combined, each cell line was allocated points based on the number of negative points (NNP) system, and the NNP sum was correlated with radioresponse.

Results: Survivin was the only factor that alone was significantly correlated with the intrinsic radiosensitivity (IR; r = 0.36, P = 0.02). The combination of survivin, Bax, Bcl‐2, Bcl‐XL, COX‐2, and the p53 Arg72Pro polymorphism was found to most strongly correlate with radioresponse (r = 0.553, P < 0.001).

Conclusion: These data indicate that the IR of 42 HNSCC cell lines can be predicted by a panel of factors on both the protein and gene levels. Moreover, among the investigated factors, survivin was the most promising biomarker of radioresponse.
Original languageEnglish
Pages (from-to)739-746
JournalJournal of Oral Pathology and Medicine
Volume40
Issue number10
DOIs
Publication statusPublished - 2011
MoE publication typeA1 Journal article-refereed

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Head and Neck Neoplasms
Single Nucleotide Polymorphism
Cell Line
Mutation
Proteins
HSP70 Heat-Shock Proteins
Radiation Tolerance
p53 Genes
Epidermal Growth Factor Receptor
DNA Repair
Radiotherapy
Biomarkers
Enzyme-Linked Immunosorbent Assay
Cell Proliferation
Apoptosis
Recurrence
Therapeutics
Genes
Carcinoma, squamous cell of head and neck

Keywords

  • Bcl-2 family
  • head and neck tumors
  • p53 Arg72Pro
  • radiotherapy
  • survivin

Cite this

Farnebo, L., Jerhammer, F., Ceder, R., Grafström, R., Vainikka, L., Thunell, L., ... Roberg, K. (2011). Combining factors on protein and gene level to predict radioresponse in head and neck cancer cell lines. Journal of Oral Pathology and Medicine, 40(10), 739-746. https://doi.org/10.1111/j.1600-0714.2011.01036.x
Farnebo, Lovisa ; Jerhammer, Fredrik ; Ceder, Rebecca ; Grafström, Roland ; Vainikka, Linda ; Thunell, Lena ; Grénman, Reidar ; Johansson, Ann-Charlotte ; Roberg, Karin. / Combining factors on protein and gene level to predict radioresponse in head and neck cancer cell lines. In: Journal of Oral Pathology and Medicine. 2011 ; Vol. 40, No. 10. pp. 739-746.
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abstract = "Background: Radiotherapy is the main therapy for head and neck squamous cell carcinoma (HNSCC); however, treatment resistance and local recurrence are significant problems, highlighting the need for predictive markers. In this study, we evaluated selected proteins, mutations, and single nucleotide polymorphisms (SNPs) involved in apoptosis, cell proliferation, and DNA repair alone or combined as predictive markers for radioresponse in 42 HNSCC cell lines.Methods: The expression of epidermal growth factor receptor, survivin, Bax, Bcl‐2, Bcl‐XL, cyclooxygenase‐2 (COX‐2), and heat shock protein 70 was analyzed by ELISA. Furthermore, mutations and SNPs in the p53 gene as well as SNPs in the MDM2, XRCC1, and XRCC3 genes were analyzed for their relation to radioresponse. To enable the evaluation of the predictive value of several factors combined, each cell line was allocated points based on the number of negative points (NNP) system, and the NNP sum was correlated with radioresponse.Results: Survivin was the only factor that alone was significantly correlated with the intrinsic radiosensitivity (IR; r = 0.36, P = 0.02). The combination of survivin, Bax, Bcl‐2, Bcl‐XL, COX‐2, and the p53 Arg72Pro polymorphism was found to most strongly correlate with radioresponse (r = 0.553, P < 0.001).Conclusion: These data indicate that the IR of 42 HNSCC cell lines can be predicted by a panel of factors on both the protein and gene levels. Moreover, among the investigated factors, survivin was the most promising biomarker of radioresponse.",
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Farnebo, L, Jerhammer, F, Ceder, R, Grafström, R, Vainikka, L, Thunell, L, Grénman, R, Johansson, A-C & Roberg, K 2011, 'Combining factors on protein and gene level to predict radioresponse in head and neck cancer cell lines', Journal of Oral Pathology and Medicine, vol. 40, no. 10, pp. 739-746. https://doi.org/10.1111/j.1600-0714.2011.01036.x

Combining factors on protein and gene level to predict radioresponse in head and neck cancer cell lines. / Farnebo, Lovisa (Corresponding Author); Jerhammer, Fredrik; Ceder, Rebecca; Grafström, Roland; Vainikka, Linda; Thunell, Lena; Grénman, Reidar; Johansson, Ann-Charlotte; Roberg, Karin.

In: Journal of Oral Pathology and Medicine, Vol. 40, No. 10, 2011, p. 739-746.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Combining factors on protein and gene level to predict radioresponse in head and neck cancer cell lines

AU - Farnebo, Lovisa

AU - Jerhammer, Fredrik

AU - Ceder, Rebecca

AU - Grafström, Roland

AU - Vainikka, Linda

AU - Thunell, Lena

AU - Grénman, Reidar

AU - Johansson, Ann-Charlotte

AU - Roberg, Karin

PY - 2011

Y1 - 2011

N2 - Background: Radiotherapy is the main therapy for head and neck squamous cell carcinoma (HNSCC); however, treatment resistance and local recurrence are significant problems, highlighting the need for predictive markers. In this study, we evaluated selected proteins, mutations, and single nucleotide polymorphisms (SNPs) involved in apoptosis, cell proliferation, and DNA repair alone or combined as predictive markers for radioresponse in 42 HNSCC cell lines.Methods: The expression of epidermal growth factor receptor, survivin, Bax, Bcl‐2, Bcl‐XL, cyclooxygenase‐2 (COX‐2), and heat shock protein 70 was analyzed by ELISA. Furthermore, mutations and SNPs in the p53 gene as well as SNPs in the MDM2, XRCC1, and XRCC3 genes were analyzed for their relation to radioresponse. To enable the evaluation of the predictive value of several factors combined, each cell line was allocated points based on the number of negative points (NNP) system, and the NNP sum was correlated with radioresponse.Results: Survivin was the only factor that alone was significantly correlated with the intrinsic radiosensitivity (IR; r = 0.36, P = 0.02). The combination of survivin, Bax, Bcl‐2, Bcl‐XL, COX‐2, and the p53 Arg72Pro polymorphism was found to most strongly correlate with radioresponse (r = 0.553, P < 0.001).Conclusion: These data indicate that the IR of 42 HNSCC cell lines can be predicted by a panel of factors on both the protein and gene levels. Moreover, among the investigated factors, survivin was the most promising biomarker of radioresponse.

AB - Background: Radiotherapy is the main therapy for head and neck squamous cell carcinoma (HNSCC); however, treatment resistance and local recurrence are significant problems, highlighting the need for predictive markers. In this study, we evaluated selected proteins, mutations, and single nucleotide polymorphisms (SNPs) involved in apoptosis, cell proliferation, and DNA repair alone or combined as predictive markers for radioresponse in 42 HNSCC cell lines.Methods: The expression of epidermal growth factor receptor, survivin, Bax, Bcl‐2, Bcl‐XL, cyclooxygenase‐2 (COX‐2), and heat shock protein 70 was analyzed by ELISA. Furthermore, mutations and SNPs in the p53 gene as well as SNPs in the MDM2, XRCC1, and XRCC3 genes were analyzed for their relation to radioresponse. To enable the evaluation of the predictive value of several factors combined, each cell line was allocated points based on the number of negative points (NNP) system, and the NNP sum was correlated with radioresponse.Results: Survivin was the only factor that alone was significantly correlated with the intrinsic radiosensitivity (IR; r = 0.36, P = 0.02). The combination of survivin, Bax, Bcl‐2, Bcl‐XL, COX‐2, and the p53 Arg72Pro polymorphism was found to most strongly correlate with radioresponse (r = 0.553, P < 0.001).Conclusion: These data indicate that the IR of 42 HNSCC cell lines can be predicted by a panel of factors on both the protein and gene levels. Moreover, among the investigated factors, survivin was the most promising biomarker of radioresponse.

KW - Bcl-2 family

KW - head and neck tumors

KW - p53 Arg72Pro

KW - radiotherapy

KW - survivin

U2 - 10.1111/j.1600-0714.2011.01036.x

DO - 10.1111/j.1600-0714.2011.01036.x

M3 - Article

VL - 40

SP - 739

EP - 746

JO - Journal of Oral Pathology and Medicine

JF - Journal of Oral Pathology and Medicine

SN - 0904-2512

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ER -