Expression of Class III Beta-Tubulin Correlates with Unfavorable Survival Outcome in Patients with Resected Non-small Cell Lung Cancer

Koh, Youngil; Jang, Bo Gun; Han, Sae Won; Kim, Tae Min; Oh, Do Youn; Lee, Se‐Hoon; Kang, Chang Hyun; Kim, Dong Wan; Im, Seock Ah; Chung, Doo Hyun; Kim, Young Tae; Kim, Young Whan; Kim, Joo Hyun; Heo, Dae Seog; Bang, Yung Jue

doi:10.1097/jto.0b013e3181ce684f

Cited by 52 publications

(41 citation statements)

References 31 publications

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“…TUBB3 has been investigated to determine the role of this gene in resistance to paclitaxel and docetaxel. TUBB3 is also an independent prognostic marker in patients with resected NSCLC that have not received chemotherapy (38)(39)(40). In the present study, the expression of RRM1 andTUBB3 was not associated with the DFS time of patients with NSCLC that received adjuvant cisplatin-based chemotherapy.…”

Section: Discussioncontrasting

confidence: 42%

Analysis of ERCC1, BRCA1, RRM1 and TUBB3 as predictors of prognosis in patients with non-small cell lung cancer who received cisplatin-based adjuvant chemotherapy: A prospective study

et al. 2015

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Abstract. Although adjuvant platinum-based chemotherapy has been demonstrated to improve survival in patients with completely resected non-small cell lung cancer (NSCLC), individualized approaches to therapy are urgently required to improve the treatment efficacy and reduce unnecessary toxicity. It was hypothesized in the present study that the protein levels of excision repair cross-complementation group 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase M1 (RRM1) and class III β-tubulin (TUBB3) may influence the therapeutic effect of adjuvant cisplatin-based chemotherapy. The expression of ERCC1, BRCA1, RRM1 and TUBB3 in tissues obtained from 84 patients with NSCLC was analyzed in the present non-interventional study by immunohistochemistry prior to adjuvant chemotherapy. All patients received adjuvant cisplatin-based chemotherapy. The primary endpoint in the present study was disease free survival (DFS). Out of the 84 tumors, the expression of ERCC1, BRCA1, RRM1 and TUBB3 was identified in 46 (55%), 11 (13%), 73 (87%) and 76 (90%) tissues, respectively. A beneficial response to adjuvant cisplatin-based chemotherapy in DFS was associated with the absence of the expression of ERCC1 [hazard ratio (HR), 2.166; 95% confidence interval (CI), 1.049-4.474; P=0.037] and BRCA1 (HR, 2.419; 95% CI, 1.127-5.193; P=0.023), but not with the expression status of RRM1 (HR, 0.568; 95% CI, 0.234-1.379; P=0.212) or TUBB3 (HR, 1.874; 95% CI, 0.448-7.842; P=0.39). In addition, patients lacking the expression of ERCC1 and BRCA1 benefited more from adjuvant cisplatin-based chemotherapy compared with patients that expressed either ERCC1 or BRCA1 (HR, 3.102; 95% CI, 1.343-7.163; P=0.008). The expression of ERCC1 and BRCA1 was significantly associated with the DFS time in patients with NSCLC treated with adjuvant cisplatin-based chemotherapy, respectively. The combination of the ERCC1 and BRCA1 expression levels may be a promising prognostic prediction for adjuvant cisplatin-based chemotherapy.

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Section: Discussioncontrasting

confidence: 42%

Analysis of ERCC1, BRCA1, RRM1 and TUBB3 as predictors of prognosis in patients with non-small cell lung cancer who received cisplatin-based adjuvant chemotherapy: A prospective study

et al. 2015

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“…After reading the title and abstract, 61 articles were selected to read the full articles by two investigators (ZX Zhang, XD Yin), 3 of them were excluded as the cohort was similar in other articles (studies excluded [9], [10], [11]; studies included [12], [13], [14]. Finally, 22 studies were found eligible for the systematic review which were published between 2007 and 2014 [15], [13], [16]–[24], [12], [25]–[32], [14], [33], in which 5 studies could not provide sufficient data for meta-analysis [16], [19], [20], [32], [14]. Figure 1 shows the flow chart of the search result.…”

Section: Resultsmentioning

confidence: 99%

“…11 studies compared the DFS between EGFR mutations and wild-type groups [18], [22], [12], [25], [26], [27], [28], [29], [30], [31], [33]. Significant heterogeneity was detected among the studies (I 2 = 62%, P = 0.003).…”

Section: Resultsmentioning

confidence: 99%

Prognostic Value of Epidermal Growth Factor Receptor Mutations in Resected Non-Small Cell Lung Cancer: A Systematic Review with Meta-Analysis

et al. 2014

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BackgroundThe prognostic value of epidermal growth factor receptor (EGFR) mutations in resected non-small cell lung cancer (NSCLC) remains controversial. We performed a systematic review with meta-analysis to assess its role.MethodsStudies were identified via an electronic search on PubMed, Embase and Cochrane Library databases. Pooled hazard ratio (HR) for disease-free survival (DFS) and overall survival (OS) were calculated for meta-analysis.ResultsThere were 16 evaluated studies (n = 3337) in the meta-analysis. The combined HR evaluating EGFR mutations on disease free survival was 0.96 (95% CI [0.79–1.16] P = 0.65). The combined HR evaluating EGFR mutations on overall survival was 0.86 (95% CI [0.72–1.04] P = 0.12). The subgroup analysis based on univariate and multivariate analyses in DFS and OS showed no statistically significant difference. There was also no statistically significant difference in DFS and OS of stage I NSCLC patients.ConclusionThe systematic review with meta-analysis showed that EGFR mutations were not a prognostic factor in patients with surgically resected non-small cell lung cancer. Well designed prospective study is needed to confirm the result.

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“…Hence, an individual or crowd capable of obtaining benefits most from chemotherapy is screened out by detecting biological indicators like genes and proteins, which is of great importance to realize NSCLC individualized treatment, improve individual therapeutic effects and decrease toxic and side effects. Detecting the expression levels of RRM1, ERCC1 and BRCA1 genes in tumor tissue to screen out the patients sensitive to capecitabine is a hot topic in the field of lung cancer at present (Lee et al, 2008;Koh et al, 2010;Hubner et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

mRNA Expression and Clinical Significance of ERCC1, BRCA1, RRM1, TYMS and TUBB3 in Postoperative Patients with Non-Small Cell Lung Cancer

Han

Wang²,

Xiao³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: To explore mRNA expression and clinical significance of ERCC1, BRCA1, RRM1, TYMS and TUBB3 genes in tumor tissue of postoperative patients with non-small cell lung cancer (NSCLC). Materials and Methods: Sixty NSCLC patients undergoing radical operation in our hospital from Nov., 2011 to Jun., 2012 were selected. Plasmid standards of ERCC1, BRCA1, RRM1, TYMS and TUBB3 were established and standard curves were prepared by SYBR fluorescent real-time quantitative PCR analysis. Samples from tumor centers were taken to detect mRNA expression of ERCC1, BRCA1, RRM1, TYMS and TUBB3 genes in cancerous tissue during operation. The total mRNA expression quantities were compared according to different clinical characteristics. Results: The total expression quantities of 5 genotypes from high to low were ERCC1>RRM1>TUBB3>TYMS>BRCA1 in turn. By pairwise comparisons, other differences showed statistical significance (p<0.05 or p<0.01) except for TYMS and TUBB3 (p>0.05); the low expression rates from high to low were ERCC1>TYMS>TUBB3>TUBB3>RRM1>BRCA1 in turn. The expression quantities of BRCA1, RRM1 and TYMS in males, smokers and patients without adenocarcinoma were all significantly higher than that in females, non-smokers and patients with adenocarcinoma, and significant differences were present (p<0.05 or p<0.01). In terms of pathological staging, the expression quantities of BRCA1, RRM1 and TYMS in phases Ⅱa~Ⅱb and Ⅲa~Ⅲb had a tendency to be greater than in phases Ⅰ and Ⅳ. Conclusions: Resistance to chemotherapy and sensitivity to targeted therapy differ among patients with NSCLC. Differences in gene expression in different individuals were also revealed. Only according to personalized detection results can individualized therapeutic regimens be worked out, which is a new direction for oncotherapy.

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Expression of Class III Beta-Tubulin Correlates with Unfavorable Survival Outcome in Patients with Resected Non-small Cell Lung Cancer

Abstract: TUBB3 expression is an independent unfavorable prognostic marker in patients with curatively resected non-small cell lung cancer who did not receive adjuvant chemotherapy.

Cited by 52 publications

References 31 publications

Analysis of ERCC1, BRCA1, RRM1 and TUBB3 as predictors of prognosis in patients with non-small cell lung cancer who received cisplatin-based adjuvant chemotherapy: A prospective study

Analysis of ERCC1, BRCA1, RRM1 and TUBB3 as predictors of prognosis in patients with non-small cell lung cancer who received cisplatin-based adjuvant chemotherapy: A prospective study

Prognostic Value of Epidermal Growth Factor Receptor Mutations in Resected Non-Small Cell Lung Cancer: A Systematic Review with Meta-Analysis

mRNA Expression and Clinical Significance of ERCC1, BRCA1, RRM1, TYMS and TUBB3 in Postoperative Patients with Non-Small Cell Lung Cancer

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