A four-marker signature of TNF-RII, TGF-α, TIMP-1 and CRP is prognostic of worse survival in high-risk surgically resected melanoma

Abstract

BackgroundE1694 tested GM2-KLH-QS21 vaccine versus high-dose interferon-α2b (HDI) as adjuvant therapy for operable stage IIB-III melanoma. We tested banked serum specimens from patients in the vaccine arm of E1694 for prognostic biomarkers.MethodsAushon Multiplex Platform was used to quantitate baseline serum levels of 115 analytes from 40 patients. Least absolute shrinkage and selection operator proportional hazard regression (Lasso PH) was used to select markers that are most informative for relapse-free survival (RFS) and overall survival (OS). Regular Cox PH models were then fit with the markers selected by the Lasso PH. Survival receiver operating characteristic (ROC) analysis was used to evaluate the ability of the models to predict 1-year RFS and 5-year OS.ResultsFour markers that include Tumor Necrosis Factor alpha Receptor II (TNF-RII), Transforming Growth Factor alpha (TGF-α), Tissue Inhibitor of Metalloproteinases 1 (TIMP-1), and C-reactive protein (CRP) were found to be most informative for the prediction of OS (high levels correlate with worse prognosis). The dichotomized risk score based on the four markers could significantly separate the OS curves (p = 0.0005). When using the four-marker PH model to predict 5-year OS, we achieved an area under the curve (AUC) of 89% (cross validated AUC = 72%). High baseline TNF-RII was also significantly associated with worse RFS. The RFS with high (above median) TNF-RII was significantly lower than low TNF-RII (p = 0.01).ConclusionsThe biomarker signature consisting of TNFR-II, TGF-α, TIMP-1 and CRP is significantly prognostic of survival in patients with high-risk melanoma and warrants further investigation.

Hypertension and Circulating Cytokines and Angiogenic Factors in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma Treated With Sunitinib: Results From a Phase II Trial

“…Similarly, TGF-a has been associated with prognosis or a poor response to treatment in a number of cancers, but no data were previously available for RCC [36][37][38]. A member of the epidermal growth factor (EGF) family and a ligand of the EGF receptor, TGF-a is upregulated by hypoxia-inducible factor in RCC and was found sufficient to promote the growth of ccRCC tumor cells [39].…”

Inflammation markers in cutaneous melanoma - edgy biomarkers for prognosis

“…High levels of circulating biomarkers associated with poor prognosis in melanoma patients (TNFR2, TGF-alpha, TIMP1, CRP) were recently identified by multiplex technology and described as being part of a valuable formula for overall survival prediction (OS) 86 .…”

Abnormalities in soluble CD147 / MMPs / TIMPs axis in Ankylosing Spondylitis patients with and without a history of Acute Anterior Uveitis / Anomalii ale axei CD147 solubil / MMPs / TIMPs la pacienții cu spondilită anchilozantă cu sau fără uveită acută anterioară

“…The correlation with Fb level was not unexpected since other groups of researchers have already demonstrated Fb role in cell activation and subsequently in MMPs production (46) Furthermore, Tarhini et al (47) demonstrated a relationship between TIMP-1 and CRP; these biomarkers by their multiple activities have significant prognostic capacity in patients with melanoma. These results underline the potential role of inflammation mediators (Fb and CRP) in the dysregulation of the balance between MMPs inducer, MMPs and MMPs inhibitors which contribute to chronic inflammation and tissue damage in AS patients.…”