Evaluation of nuclear NF-κB, transglutaminase2, and ERCC1 as predictors of platinum resistance in testicular tumors

Abstract

Purpose: Testicular germ cells tumor (TGCT) are associated with a high cure rate and are treated with platinum-based chemotherapy. However, a group of testicular cancer patients may have a very unfavorable evolution and insensitivity to the main therapeutic agent chemotherapy (CT) cisplatin. The aim of this study was to evaluate the risk of recurrence and overall survival related to the expression of nuclear factor kappa-B (NF-κB), transglutaminase 2 (TG2) and excision repair cross-complementation group 1 (ERCC1) in patients with TGCT treated with platinum combinations. Patients and Methods: A retrospective study was performed with TGCT patients treated with platinum-based chemotherapy. Immunohistochemical analysis was performed and the expression was correlated with clinical and laboratory data. Results: Fifty patients were included, the mean age was 28.4 years (18 to 45), and 76% were non-seminoma. All patients were treated with standard cisplatin, etoposide and bleomycin or cisplatin, and etoposide. Patient's analyzed immunodetection for NF-κB, TG2, and ERCC1 were positive in 76%, 54% and 42%, respectively. Multivariate analysis identifi ed that positive expressions to ERCC1 and NF-κB are independent risk factors for higher recurrence TGCT after chemotherapy (RR 2.96 and 3.16, respectively). Patients with positive expression of ERCC1 presented a poor overall survival rate for 10-year follow (p=0.001). Conclusions: The expression of ERCC1 and NF-κB give a worse prognosis for relapse, and only ERCC1 had an infl uence on the overall survival of TGCT patients treated with platinum-based chemotherapy. These may represent markers that predict poor clinical outcome and response to cisplatin.

Exosomal ERp44 derived from ER-stressed cells strengthens cisplatin resistance of nasopharyngeal carcinoma

“…Transcription factor nuclear factor kappa-B (NF-κB) is involved in cell apoptosis and platinum-based chemotherapy resistance [32]. We confirmed that in CNE2, when ERp44 was overexpressed, p-NF-κB was increased, while when ERp44 was downregulated, it was decreased (Fig.…”

“…In oral squamous cancer cell carcinoma (OSCC), when ERp44 was downregulated, cell proliferation was reduced, while apoptosis was significantly induced [19]. NF-κB has been described to be involved in cell apoptosis and platinum-based chemotherapy resistance [32]. In nonsmall-cell lung cancer (NSCLC), NF-κB was a potential therapeutic target in cisplatin-resistant cells [44].…”

Female Germ Cell Development, Functioning and Associated Adversities under Unfavorable Circumstances

“…A number of factors are involved in GCT response to chemotherapy among which variable efficiency of the DNA damage response activation constitutes a major target. Associated factors include excision repair cross-complementation group 1 (ERCC1) expression [111], checkpoint kinase 2 (CHEK2) activation [112], and homologous recombination repair pathways activation [113,114]. These factors can be efficiently used in evaluation of GCT susceptibility in response to chemotherapeutic agents.…”