The Prognostic Value of Excision Repair Cross-Complementation Group 1 (ERCC1) in Patients with Small Cell Lung Cancer (SCLC) Receiving Platinum-Based Chemotherapy: Evidence from Meta-Analysis

Abstract

Recently, the correlation between the efficacy of platinum-based chemotherapy and ERCC1 expression in patients with SCLC has attracted wide-spread attention, and a lot of investigations have been conducted, whereas conflicting results were presented. Therefore, we performed the present meta-analysis of eligible studies to derive a more precise evaluation of the association between ERCC1 expression and the clinical outcome in SCLC patients receiving platinum-based chemotherapy. A literature search for relevant studies was conducted in the electronic databases of PubMed, EMBASE and Web of Science. The inclusive criteria were SCLC patients treated by platinum-based chemotherapy, and evaluated the relationship between ERCC1 expression and the clinical outcomes [including overall response rate (ORR), overall survival (OS) or progression-free survival (PFS)]. Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) was calculated to assess the risk. A total of nine studies including 1129 patients were included in final analysis. Our analysis indicated that positive/high ERCC1 expression was associated with unfavorable OS (HR = 1.18, 95%CI = 1.02–1.37) and PFS (HR = 1.46, 95%CI = 1.14–1.88). Subgroup analysis according to disease stage suggested the significant relationship was found in limited stage (LS-SCLC), but not in extensive stage (ES-SCLC). However, no significant association was found between ERCC1 expression and ORR. Our analysis suggested ERCC1 expression may be a prognostic factor in SCLC patients receiving platinum-based chemotherapy, especially for LS-SCLC.

Excision Repair Cross-complementation Group 1 is a Prognostic Biomarker in Patients with Colorectal Cancer Receiving Chemotherapy

“…[ 28 ] The present meta-analysis, chiefly focused on patients underwent chemotherapy, revealed that patients with increased expression of ERCC1 predisposed to be resistant to chemotherapy and a short PFS, and OS was very likely the consequence. It was consistent with the theoretical inference and the analogous meta-analyses assessing the prognostic value of ERCC1 in gastric cancer,[ 29 ] small cell lung cancer,[ 30 ] and nonsmall cell lung cancer. [ 31 ] Thus, we inferred that ERCC1 might be employed as an indicator of therapy effects and the survival outcome.…”

In Silico Evaluation of Pharmacokinetic Optimization for Antimitogram-Based Clinical Trials

“…In combination with PKO, other useful PDO strategies may also be used, such as adaptation to protein, epigenetic, or genetic markers recognized for their treatment-specific prognostic value (27)(28)(29)(30), or biological early efficacy markers (31,32). One such example of PDO, the use of targeted therapy tailored to genetic aberrations, has been tested in a negative trial (33), which could have had different results under the PKPDO paradigm, because most of its drugs have clinically relevant exposure-response relationships (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44).…”

DNA Repair Endonucleases: Physiological Roles and Potential as Drug Targets

“…65 Preclinical studies in several cancer cell lines, including ovarian, cervical, and lung, support the hypothesis that overexpression of ERCC1 correlates with resistance to platinum-based therapies. [66][67][68][69] In a large-scale study into lung cancer treatment, it was shown that patients with ERCC1-negative tumors benefited significantly more from cisplatin treatment, whereas patients with ERCC1-positive tumors did not respond to treatment and had a poorer prognosis. 70 Furthermore, an investigation in colorectal cancer demonstrated that patients with low expression of ERCC1 had a significantly greater median survival in comparison to those expressing high levels of ERCC1, although there was no correlation with response to 5-fluoracil/oxaliplatin treatment.…”