Proteins and single nucleotide polymorphisms involved in apoptosis, growth control, and DNA repair predict cisplatin sensitivity in head and neck cancer cell lines

Farnebo, Lovisa; Jedliński, Adam; Ansell, Anna; Vainikka, Linda; Thunell, Lena K.; Grénman, Reidar; Johansson, Ann-Charlotte; Roberg, Karin

doi:10.3892/ijmm_00000264

Cited by 8 publications

References 25 publications

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Tyrosine kinase domain mutations of <em>EGFR</em> gene in head and neck squamous cell carcinoma

Vatte

Amri

Cyrus

et al. 2017

OTT

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BackgroundEpidermal growth factor receptor (EGFR) is a commonly altered gene that is identified in various cancers, including head and neck squamous cell carcinoma (HNSCC). Therefore, EGFR is a promising molecular marker targeted by monoclonal antibodies and small molecule inhibitors targeting the tyrosine kinase (TK) domain.ObjectiveThe objective of this study was to investigate the spectrum of mutations in exons 18, 19, 20, and 21 of the EGFR gene in HNSCC patients.Materials and methodsThis retrospective study included 47 confirmed HNSCC cases. Mutations in the TK domain, exons 18, 19, 20, and 21 of the EGFR gene, were detected by Scorpion® chemistry and ARMS® technologies on Rotor-Gene Q real-time polymerase chain reaction.ResultsThe tumors exhibited EGFR-TK domain mutations in 57% of cases. Four cases of T790M mutations were reported for the first time among HNSCC patients. Out of the total mutations, L861Q (exon 21), exon 20 insertions and deletions of exon 19 accounted for the majority of mutations (21%, 19%, and 17%, respectively). EGFR mutation status was correlated with the higher grade (P=0.026) and advanced stage (P=0.034) of HNSCC tumors.ConclusionHigher frequency of EGFR-TK domain mutations together with the presence of the T790M mutation suggests that identification of these mutations might streamline the therapy and provide a better prognosis in HNSCC cases.

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Tyrosine kinase domain mutations of <em>EGFR</em> gene in head and neck squamous cell carcinoma

Vatte

Amri

Cyrus

et al. 2017

OTT

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Identification of Tumor Cell- and Stroma Derived Biomarkers of Treatment Response in Head and Neck Cancer

Ansell¹

2013

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V ABSTRACTHead and neck squamous cell carcinoma (HNSCC) poses a major health problem in the world with approximately 600 000 new cases yearly. Treatment resistance is a major problem within this patient group and despite advances in treatment strategies the overall survival rate has unfortunately not increased.One of the major components of the tumor microenvironment is the cancer associated fibroblasts (CAFs) which can modulate the treatment sensitivity, tumor growth, and the invasive potential of tumor cells.The aim of this thesis was to identify predictive markers for treatment response in HNSCC and to study the crosstalk between tumor cells and CAFs that may underlie treatment resistance.In paper I, we identified gene expression differences between one cisplatin sensitive cell line and two cisplatin resistant cell lines, by microarray analysis, and found that a high expression of matrix metalloproteinase (MMP) -7 was associated with resistance to cisplatin. In paper II, the epidermal growth factor (EGF) receptor ligands EGF, amphiregulin, and epiregulin were evaluated regarding their potential use as predictive biomarkers for cetuximab treatment response in tongue cancer cell lines and it was shown that EGF may serve as a marker for poor cetuximab response. In paper III and IV, we investigated the influence of CAFs on the proliferation, migration, gene expression, and cetuximab response of tumor cells. It was found that CAFs induced resistance to cetuximab in a MMP-dependent manner. In addition, a microarray analysis, ABSTRACT VI comparing tumor cells co-cultured with CAFs and tumor cells cultured alone, revealed that CAFs induced multiple gene expression changes in tumor cells some of which are related to epithelial to mesenchymal transition. Some of these changes were found to be dependent on cell-cell contact.Taken together, we here suggest MMP-7 and EGF to be predictive markers of cisplatin and cetuximab response, respectively. We also show that CAFs protect HNSCC cells from cetuximab treatment; however, the factor responsible for the protective effect is yet to be discovered.

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Revealing the causal role of immune cells in malignant neoplasms of the head and neck: insights from Mendelian randomization

Zhou,

Yuan,

Zhong

et al. 2024

Front. Oncol.

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BackgroundImmune escape and immunosuppression play crucial roles in the onset and progression of head and neck malignant neoplasms (HNMN). However, previous studies on the relationship between immune cells and HNMN have yielded inconsistent results.MethodsIn this study, we performed bidirectional two-sample Mendelian randomisation (MR) analyses using genome-wide association study (GWAS) and FinnGen databases to examine the association between 731 immune cell features and the risk of HNMN. We conducted sensitivity analyses to assess the robustness of the findings.ResultsSubsequent to false discovery rate (FDR) correction, three immune cell phenotypes were found to have a significant correlation with the risk of HNMN: CD28−CD8+ absolute cells (AC) (inverse-variance weighted [IVW] using the multiplicative random effects model: OR [95%]: 1.325 [1.413 to 1.539], P = 0.0002, Pfdr = 0.054), CD3 on secreting Treg (IVW: OR [95%]: 0.887 [0.835 to 0.941], P = 0.00007, Pfdr = 0.025), and CD3 on resting Treg (IVW: OR [95%]: 0.891 [0.842 to 0.943], P = 0.00006, Pfdr = 0.026). The results of the sensitivity analysis were aligned with the primary findings. No statistically significant effects of HNMN on the immunophenotypes were observed.ConclusionsOur research indicates causal relationships among the three immune cell phenotypes and vulnerability to HNMN, providing new insights into immune infiltration within the HNMN tumour microenvironment and the development of immunotherapy drugs targeting checkpoint inhibitors of HNMN.

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Proteins and single nucleotide polymorphisms involved in apoptosis, growth control, and DNA repair predict cisplatin sensitivity in head and neck cancer cell lines

Cited by 8 publications

References 25 publications

Tyrosine kinase domain mutations of <em>EGFR</em> gene in head and neck squamous cell carcinoma

Tyrosine kinase domain mutations of <em>EGFR</em> gene in head and neck squamous cell carcinoma

Identification of Tumor Cell- and Stroma Derived Biomarkers of Treatment Response in Head and Neck Cancer

Revealing the causal role of immune cells in malignant neoplasms of the head and neck: insights from Mendelian randomization

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