Prognostic effect of class III β-tubulin and Topoisomerase-II in patients with advanced thymic carcinoma who received combination chemotherapy, including taxanes or topoisomerase-II inhibitors

Abstract

Class III β-tubulin (TUBB3) and Topoisomerase-II (topo-II) are considered to be the predictors of therapeutic efficacy and outcome in several types of human neoplasm. However, whether TUBB3 or topo-II may predict the response to combination chemotherapy and prognosis in patients with advanced thymic carcinoma (ATC) remains unclear. The aim of the present study was to investigate the prognostic significance of TUBB3 and topo-II expression levels in ATC. A total of 34 patients with ATC who received combination chemotherapy were enrolled in the present study. Immunohistochemical analysis was used to examine the expression of TUBB3, topo-II and Ki-67 in tumor specimens obtained by surgical resection or biopsy. TUBB3 and topo-II were highly expressed in 38 and 53% of the tumors, respectively. Progression-free survival (PFS) was significantly shorter in patients with high levels of TUBB3 compared with those with low levels of TUBB3 (P<0.01), whereas no significant difference in PFS between patients with high and low topo-II expression levels was observed (P=0.31). Patients with overexpression of TUBB3 or topo-II exhibited significantly shorter overall survival rates (OS) compared with those patients with low levels of expression of these proteins (TUBB3; P=0.01, topo-II; P=0.01). Multivariate analysis demonstrated that a high level of TUBB3 expression was an independent unfavorable prognostic factor for OS, and a high level of topo-II expression tended to correlate with poor prognosis without statistical significance. Additionally, a subset analysis demonstrated that the treatment with taxanes, but not topo-II inhibitors, tended to prolong OS in patients with TUBB3 overexpression and there was significant survival advantage of chemoradiotherapy over chemotherapy in patients with topo-II overexpression. It was revealed that an enhanced expression of TUBB3 or topo-II was clearly associated with clinical outcomes in patients with ATC who received combination chemotherapy, including taxanes or topo-II inhibitors, suggesting the prognostic significance of these markers.

The oncogenic role of LGR6 overexpression induced by aberrant Wnt/β‐catenin signaling in lung cancer

“…Tumors with a score ≥3 were considered to have high expression levels. The Ki‐67 labeling index was calculated as the percentage of stained cells in each sample 34 …”

“…The Ki-67 labeling index was calculated as the percentage of stained cells in each sample. 34 Transcriptome analyses mRNA sequencing comparing the expression profiles of LGR6-silenced and LGR6-retained CTNNB1-mutated NSCLC cell lines (HCC15 and A427), or comparing those of sphere-forming and adherent A427 cells were performed as described previously. 35 Purified RNA quality was evaluated by the RNA integrity number (RIN) using the Agilent RNA6000 Pico kit and Agilent 2100 Bioanalyzer (Agilent Technologies).…”