Clinical significance of head and neck squamous cell cancer biomarkers

Polanská, Hana; Raudenská, Martina; Gumulec, Jaromír; Sztalmachová, Markéta; Adam, Vojtěch; Kizek, René; Masařík, Michal

doi:10.1016/j.oraloncology.2013.12.008

Cited by 89 publications

(75 citation statements)

References 141 publications

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“…However, there is still a considerable variation in the prognosis within a group of patients sharing the same clinicopathological characteristics. No clinically useful prognostic biomarkers similar to the HER2 or oestrogen receptor in breast cancers [6], nor PSA in prostate [7] have been found yet for HNSCC [8]. Accordingly, an assessment of the mRNA expressing patterns of particular tumours should be useful.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of the tumour-adjacent tissue in head and neck cancers

et al. 2015

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Even with significant advances in operative skills and adjuvant therapies, the overall survival of patients suffering with head and neck squamous cancers (HNSCC) is unsatisfactory. Accordingly, no clinically useful prognostic biomarkers have been found yet for HNSCC. Many studies analysed the expression of potential markers in tumour tissues compared to adjacent tissues. Nevertheless, due to the sharing of the same microenvironment, adjacent tissues show molecular similarity to tumour tissues. Thus, gene expression patterns of 94 HNSCC tumorous tissues were compared with 31 adjacent tissues and with 10 tonsillectomy specimens of non-cancer individuals. The genes analysed at RNA level using quantitative RT-PCR and correlated with clinico-pathological conditions were as follows: EGF, EGFR, MKI67, BCL2, BAX, FOS, JUN, TP53, VEGF, FLT1, MMP2, MMP9, MT1A and MT2A. The elevated MT2A, BAX, EGF and JUN expression was associated with the influence of tumour cells on the rearrangement of healthy tissues, as well as a significant shift in the BAX/BCL2 ratio. Our investigation also indicated that adjacent tissues play an important role in cancerogenesis by releasing several tumour-supporting factors such as EGF. A gradual increase in the metallothionein expression, from the lowest one in tonsillectomy samples to the highest ones in tumour samples, suggests that MT expression might be tissue reaction to the presence of tumour cells. The results of this study confirmed the significance of metallothionein in tumori-genesis and gave evidences for its use as a potential HNSCC biomarker. Furthermore, this study highlighted the importance of histologically normal tumour-adjacent tissue in prediction of HNSCC progress.

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Section: Introductionmentioning

confidence: 99%

Prognostic significance of the tumour-adjacent tissue in head and neck cancers

et al. 2015

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“…The resulting increased pathway activation by Wnt ligand proteins leads to the accumulation of β-catenin and ultimately the increased expression of transcription factors and cell-cycle control proteins involved in tumorigenesis including Cyclin D [36, 37]. Cyclin D has been shown to be upregulated in HNSCC, particularly those not associated with HPV [3, 38]. Interestingly, the epidermal growth factor receptor (EGFR), an important pathway in HNSCC and current target for treatment [39], and Wnt signaling pathways have potential crosstalk via β-catenin [40].…”

Section: Discussionmentioning

confidence: 99%

“…Early detection of HNSCC is a key factor for improving the survival rate of HNSCC patients; however, a high proportion of patients are diagnosed at an advanced stage [3]. The heterogeneous nature of HNSCC location and smoking or HPV etiology further strengthen the need for improved personalized assessment of the disease.…”

Section: Introductionmentioning

confidence: 99%

Expression of the extracellular sulfatase SULF2 is associated with squamous cell carcinoma of the head and neck

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Zhou

et al. 2016

Oncotarget

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Sulfatase 2 (SULF2), an extracellular sulfatase that alters sulfation on heparan sulfate proteoglycans, is involved in the tumorigenesis and progression of several carcinomas. SULF2 expression has not been evaluated in squamous cell carcinoma of the head and neck (HNSCC). Here we report results of IHC of SULF2 expression in HNSCC tissue. SULF2 was detected in 57% of tumors (n = 40) with a significant increase in intensity and number of stained cells compared to adjacent cancer-free tissue (p-value < 0.01), increasing with cancer stage when comparing stages 1 and 2 to stages 3 and 4 (p-value 0.01). SULF2 was not detected in epithelial cells of cancer-free controls, and expression was independent of patient demographics, tumor location and etiological factors, smoking and HPV infection by p16 IHC analysis. Sandwich ELISA was performed on serum of HNSCC patients (n = 28) and controls (n = 35), and although SULF2 was detectable, no change was observed in HNSCC. Saliva, collected by mouthwash, from HNSCC patients (n = 8) and controls (n = 8) was also tested by ELISA in a preliminary investigation and an increase in SULF2 was observed in HNSCC (p-value 0.041). Overall, this study shows that SULF2 is increased in HNSCC independent of tissue location (oral cavity, oropharynx, larynx and hypopharynx), patient demographics and etiology. Although no change in SULF2 was detected in HNSCC serum, its detection in saliva makes it worthy of further investigation as a potential HNSCC biomarker.

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“…Numerous studies have shown that EGFR is overexpressed in HNSCC tumor tissue, but only few studies focused on soluble EGFR levels (24)(25)(26). There are contradictory studies on soluble EGFR levels, which could be either decreased or elevated in cancer patients compared with a healthy cohort.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of EGFR as a prognostic and diagnostic marker for head and neck squamous cell carcinoma patients

et al. 2016

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Abstract. Approximately 90% of all head and neck tumors are squamous cell carcinomas. The overall survival of patients with head and neck squamous cell carcinoma (HNSCC) is low (≤50%). A non-invasive marker of disease progression is sorely required. The present study focused on the plasmatic levels of epidermal growth factor receptor (EGFR) in HNSCC patients (N=92) compared with healthy (N=29) and diabetic [type 2 diabetes mellitus (T2DM); N=26] controls. Enzymelinked immunosorbent assay using antibodies against the extracellular region of EGFR (L25-S645) was performed. No significant changes were observed between diabetic and healthy controls. However, there were significantly higher EGFR plasma levels in HNSCC patients compared with both control groups (P=0.001 and 0.005, respectively). Receiver operating characteristic curve analysis identified a sensitivity of 76.09%, a specificity of 67.27% and an area under curve of 0.727 for this comparison. No significant association was observed between EGFR plasma levels and tumor stage, tumor grade, lymph node or distant metastasis occurrence, smoking habit or hypertension. However, the presence of human papillomavirus infection and T2DM in HNSCC patients had borderline effect on the plasma EGFR levels. Survival analysis revealed no significant influence of plasmatic EGFR levels on the overall and disease-specific survival of HNSCC patients. In conclusion, EGFR plasma levels appear to be a relatively promising diagnostic, but poor prognostic, HNSCC marker.

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Clinical significance of head and neck squamous cell cancer biomarkers

Cited by 89 publications

References 141 publications

Prognostic significance of the tumour-adjacent tissue in head and neck cancers

Prognostic significance of the tumour-adjacent tissue in head and neck cancers

Expression of the extracellular sulfatase SULF2 is associated with squamous cell carcinoma of the head and neck

Evaluation of EGFR as a prognostic and diagnostic marker for head and neck squamous cell carcinoma patients

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