Abstract
Objective To investigate the clinical significance of the mRNA expression of RRM1, TUBB3, and ERCC1 in non-small-cell lung cancer (NSCLC) tissues for the selection of adjuvant/postoperative chemotherapy regimens. Methods Patients diagnosed with stage Ib-IIIa NSCLC were enrolled and randomly divided into a control group (undetected group) and an experimental group (detected group) after radical operation. The control group randomly received chemotherapy with gemcitabine plus cisplatin or paclitaxel plus cisplatin. The mRNA expression of RRM1, TUBB3, and ERCC1 was detected in the experimental group before chemotherapy, and based on the detected expression, the chemotherapy regimen of cisplatin plus gemcitabine or cisplatin plus paclitaxel was chosen. The disease-free survival (DFS) of the control group and experimental group was compared. Results Pathological type, stage, gene expression detection, and treatment method were not significantly correlated with DFS (P > 0.05). In the subgroups treated with gemcitabine, the median DFS was 17 months in the detected group and 10.5 months in the undetected group (hazard ratio = 0.2147, 95% confidence interval: 0.07909–0.5827, P=0.0025). Multivariate regression analysis was performed to analyse whether gene expression detection was independently correlated with DFS in the subgroups treated with gemcitabine (P=0.025). In the detected group, the prognosis of patients with low expression of RRM1 was better than that of patients with high expression of RRM1 after paclitaxel treatment (P=0.0039). Conclusions The selection of chemotherapy regimen based on mRNA expression of the RRM1, TUBB3, and ERCC1 genes may improve selection of candidate patients to receive clinical chemotherapy. However, large-scale prospective clinical studies are needed for in-depth investigation.
Highlights
Lung cancer is currently the leading cause of cancer-related death in humans, and its morbidity and mortality are constantly increasing [1]
In the 21st century, adjuvant chemotherapy is recommended for the postoperative management of stage Ib, II, and IIIa lung cancer patients as it improved the 5-year survival rate in several phase III clinical trials (ANITA and JBR10) and in a meta-analyses [3, 4]. e meta-analysis by the LACE Collaborative Group showed that surgery combined with cisplatin-based adjuvant chemotherapy Journal of Oncology significantly improved the overall survival compared with surgical treatment alone, and the 5-year absolute benefit in patients who underwent the chemotherapy was 5.4%
Its low expression is often accompanied by an increase in the incidence of lung cancer, while its high expression can cause the rapid repair of damaged DNA in cells arrested at G2/M phase, resulting in cisplatin resistance [24]
Summary
Lung cancer is currently the leading cause of cancer-related death in humans, and its morbidity and mortality are constantly increasing [1]. In the 21st century, adjuvant chemotherapy is recommended for the postoperative management of stage Ib, II, and IIIa lung cancer patients as it improved the 5-year survival rate in several phase III clinical trials (ANITA and JBR10) and in a meta-analyses [3, 4]. Erefore, the recommended standard adjuvant chemotherapy regimen for patients with NSCLC after complete surgical resection is the combined use of a platinum-based drug and a third-generation antitumour drug (gemcitabine, paclitaxel, and vinorelbine) [5]. Sensitivity to chemotherapy, both in the metastatic and in the adjuvant setting, differs by the clinicopathologic characteristics of patients [6,7,8]. As our understanding of the mechanism of chemotherapy sensitivity has advanced, it has been found that the changes in some molecular tumour markers may be related to the chemotherapy sensitivity
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