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Interleukin 4, interleukin 6 and osteopontin-serological markers of head and neck malignancy in primary diagnostics: A pilot study.

Aderhold C, Grobschmidt GM, Sauter A, Faber A, Hörmann K, Schultz JD - Oncol Lett (2014)

Bottom Line: IL-4 and osteopontin showed no significant therapy-associated alterations.Notably, IL-6 levels significantly increased post-therapeutically.With the exception of IL-6, whose levels were in fact increased following therapy, a significant therapy-associated alteration of these factors was missing.

View Article: PubMed Central - PubMed

Affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty of Mannheim, University of Heidelberg, Mannheim D-68167, Germany.

ABSTRACT
The progression of head and neck squamous cell carcinoma (HNSCC) is stimulated by various angiogenic peptides and growth factors. A correlation between tumor progression and the secretion of various serological mediators in patients with malignant tumors of the head and neck is of major interest for tumor diagnostics, evaluation of the therapy response and it may predict prognosis by specifying the individual tumor biology. Established chemotherapeutic regimes for head and neck tumors usually consist of platinum-based chemotherapeutic drugs and 5-fluorouracil (5-FU). The present pilot study sought to assess the eligibility of seven serological factors as biomarkers for malignant tumors of the head and neck: Platelet-derived growth factor, vascular endothelial growth factor, epidermal growth factor receptor, osteopontin, granulocyte-colony stimulating factor, interleukin-4 (IL-4) and IL-6. The serum levels of each factor in 20 patients receiving concomitant radiochemotherapy with cisplatin or carboplatin and 5-FU with curative intent were determined prior and subsequent to chemotherapy and were compared with 40 healthy controls. Another aim of the pilot study was to investigate whether the serum of patients showed significant differences in the concentrations of the analyzed factors at the start of concomitant radiochemotherapy compared with the controls, whether those markers indicated a neoplastic process and whether concomitant radiochemotherapy with cisplatin or carboplatin and 5-FU induced significant alterations of concentration compared with pre-therapeutic levels. The included patients were histopathologically diagnosed with HNSCC and the average age was 62.3 years. The serum samples of the patients were obtained during the course of regular pre- and post-chemotherapeutic blood draws one week prior to the start of radiochemotherapy and one week following the completion of chemotherapy. The healthy controls were collected from patients of the Sleep Laboratory of the Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital (Mannheim, Germany) without clinical evidence or laboratory signs of inflammation or history of a malignant disease. The average age was 50.3 years. The serological level of each factor was ascertained by enzyme-linked immunosorbent assay in duplicate. Serum levels of IL-4, IL-6 and osteopontin were significantly increased in patients with HNSCC compared with those in chemotherapy-naive healthy controls. IL-4 and osteopontin showed no significant therapy-associated alterations. Notably, IL-6 levels significantly increased post-therapeutically. Using logistic regression with osteopontin and IL-4, an individual risk-profile for random samples was calculated. IL-4, IL-6 and osteopontin appear to be suitable indicators of the neoplastic process as they are significantly increased in HNSCC patients compared with the control group. With the exception of IL-6, whose levels were in fact increased following therapy, a significant therapy-associated alteration of these factors was missing. Therefore, these serological markers failed to predict the therapy response, but they may be valuable as a screening instrument in primary diagnostics.

No MeSH data available.


Related in: MedlinePlus

Formula for logistic regression.
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f5-ol-08-03-1112: Formula for logistic regression.

Mentions: For multivariate analysis, logistic regression was performed with osteopontin (P=0.0003) and IL-4 (P=0.0001) to compare patients and controls (Table I). Using these results, a formula was generated in which the osteopontin and IL-4 levels of a random patient could be calculated (Fig. 5). With this formula, an individual risk figure (from 0=low risk to 1=high risk) for the emergence of HNSCC can be created, including a corresponding Youden index (sensitivity + specificity − 1), which is applied as a marker for the quality of each test. The Youden index may be a value between −1 and +1, it is reasonable to apply a diagnostic test when the value is between 0 and +1. The closer the Youden index is to +1, the higher the diagnostic quality of a test. Thus, the higher the Youden index of a patient, the higher the likelihood for developing HNSCC depending on the individual serum levels of the two combined markers (osteopontin and IL-4). The higher the Youden index, the more reliable the generated risk figure (34).


Interleukin 4, interleukin 6 and osteopontin-serological markers of head and neck malignancy in primary diagnostics: A pilot study.

Aderhold C, Grobschmidt GM, Sauter A, Faber A, Hörmann K, Schultz JD - Oncol Lett (2014)

Formula for logistic regression.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4114600&req=5

f5-ol-08-03-1112: Formula for logistic regression.
Mentions: For multivariate analysis, logistic regression was performed with osteopontin (P=0.0003) and IL-4 (P=0.0001) to compare patients and controls (Table I). Using these results, a formula was generated in which the osteopontin and IL-4 levels of a random patient could be calculated (Fig. 5). With this formula, an individual risk figure (from 0=low risk to 1=high risk) for the emergence of HNSCC can be created, including a corresponding Youden index (sensitivity + specificity − 1), which is applied as a marker for the quality of each test. The Youden index may be a value between −1 and +1, it is reasonable to apply a diagnostic test when the value is between 0 and +1. The closer the Youden index is to +1, the higher the diagnostic quality of a test. Thus, the higher the Youden index of a patient, the higher the likelihood for developing HNSCC depending on the individual serum levels of the two combined markers (osteopontin and IL-4). The higher the Youden index, the more reliable the generated risk figure (34).

Bottom Line: IL-4 and osteopontin showed no significant therapy-associated alterations.Notably, IL-6 levels significantly increased post-therapeutically.With the exception of IL-6, whose levels were in fact increased following therapy, a significant therapy-associated alteration of these factors was missing.

View Article: PubMed Central - PubMed

Affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty of Mannheim, University of Heidelberg, Mannheim D-68167, Germany.

ABSTRACT
The progression of head and neck squamous cell carcinoma (HNSCC) is stimulated by various angiogenic peptides and growth factors. A correlation between tumor progression and the secretion of various serological mediators in patients with malignant tumors of the head and neck is of major interest for tumor diagnostics, evaluation of the therapy response and it may predict prognosis by specifying the individual tumor biology. Established chemotherapeutic regimes for head and neck tumors usually consist of platinum-based chemotherapeutic drugs and 5-fluorouracil (5-FU). The present pilot study sought to assess the eligibility of seven serological factors as biomarkers for malignant tumors of the head and neck: Platelet-derived growth factor, vascular endothelial growth factor, epidermal growth factor receptor, osteopontin, granulocyte-colony stimulating factor, interleukin-4 (IL-4) and IL-6. The serum levels of each factor in 20 patients receiving concomitant radiochemotherapy with cisplatin or carboplatin and 5-FU with curative intent were determined prior and subsequent to chemotherapy and were compared with 40 healthy controls. Another aim of the pilot study was to investigate whether the serum of patients showed significant differences in the concentrations of the analyzed factors at the start of concomitant radiochemotherapy compared with the controls, whether those markers indicated a neoplastic process and whether concomitant radiochemotherapy with cisplatin or carboplatin and 5-FU induced significant alterations of concentration compared with pre-therapeutic levels. The included patients were histopathologically diagnosed with HNSCC and the average age was 62.3 years. The serum samples of the patients were obtained during the course of regular pre- and post-chemotherapeutic blood draws one week prior to the start of radiochemotherapy and one week following the completion of chemotherapy. The healthy controls were collected from patients of the Sleep Laboratory of the Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital (Mannheim, Germany) without clinical evidence or laboratory signs of inflammation or history of a malignant disease. The average age was 50.3 years. The serological level of each factor was ascertained by enzyme-linked immunosorbent assay in duplicate. Serum levels of IL-4, IL-6 and osteopontin were significantly increased in patients with HNSCC compared with those in chemotherapy-naive healthy controls. IL-4 and osteopontin showed no significant therapy-associated alterations. Notably, IL-6 levels significantly increased post-therapeutically. Using logistic regression with osteopontin and IL-4, an individual risk-profile for random samples was calculated. IL-4, IL-6 and osteopontin appear to be suitable indicators of the neoplastic process as they are significantly increased in HNSCC patients compared with the control group. With the exception of IL-6, whose levels were in fact increased following therapy, a significant therapy-associated alteration of these factors was missing. Therefore, these serological markers failed to predict the therapy response, but they may be valuable as a screening instrument in primary diagnostics.

No MeSH data available.


Related in: MedlinePlus