Prognostic role of beclin-1 in locally advanced non-small cell lung cancer in patients receiving docetaxel-platinum induction chemotherapy
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: The outcome of local treatment for advanced non-small cell lung cancer (NSCLC) remains poor, with therapies such as induction chemotherapy (IC) yielding conflicting results. This study aimed to assess the clinicopathologic and prognostic significance of the excision repair cross-complementation group 1 (ERCC1), beclin-1, and glucose-regulated protein of molecular mass 78 (GRP78) in patients with locally advanced NSCLC receiving docetaxel-platinum IC, along with efficacy and safety. Methods: This is a retrospective observational cohort study. We reviewed medical records of 31 NSCLC patients receiving docetaxel-platinum IC, and conducted immunohistochemical staining of ERCC1, beclin-1, and GRP78. Results: Response rate was 67.8% with 10.7 months of median relapse-free survival (RFS) and 23.1 months of median overall survival (OS), and no treatment-related death was reported. High expression of ERCC1, beclin-1, and GRP78 was identified in 67.7%, 87.1%, and 67.7%, respectively. Expression of ERCC1 and GRP78 did not reveal statistical significance in survival, whereas high beclin-1 expression revealed longer OS (7.6 months vs. 23.2 months; log-rank p = 0.024). In multivariate analysis, histologic differentiation (hazard ratio [HR], 3.48; p < 0.001), stage (HR, 8.5; p = 0.024), and adjuvant treatment (HR, 16.1; p = 0.001) were related to RFS, and in OS, stage (HR, 5.4; p = 0.037), adjuvant treatment (HR, 8.6; p = 0.004), and beclin-1 expression (HR, 8.2; p = 0.011) were identified as significant prognostic factors. Conclusions: Our findings suggest that high beclin-1 expression predicts longer survival in locally advanced NSCLC and docetaxel-platinum IC is a treatment option that deserves consideration.
Abstract
Background/Aims: The outcome of local treatment for advanced non-small cell lung cancer (NSCLC) remains poor, with therapies such as induction chemotherapy (IC) yielding conflicting results. This study aimed to assess the clinicopathologic and prognostic significance of the excision repair cross-complementation group 1 (ERCC1), beclin-1, and glucose-regulated protein of molecular mass 78 (GRP78) in patients with locally advanced NSCLC receiving docetaxel-platinum IC, along with efficacy and safety. Methods: This is a retrospective observational cohort study. We reviewed medical records of 31 NSCLC patients receiving docetaxel-platinum IC, and conducted immunohistochemical staining of ERCC1, beclin-1, and GRP78. Results: Response rate was 67.8% with 10.7 months of median relapse-free survival (RFS) and 23.1 months of median overall survival (OS), and no treatment-related death was reported. High expression of ERCC1, beclin-1, and GRP78 was identified in 67.7%, 87.1%, and 67.7%, respectively. Expression of ERCC1 and GRP78 did not reveal statistical significance in survival, whereas high beclin-1 expression revealed longer OS (7.6 months vs. 23.2 months; log-rank p = 0.024). In multivariate analysis, histologic differentiation (hazard ratio [HR], 3.48; p < 0.001), stage (HR, 8.5; p = 0.024), and adjuvant treatment (HR, 16.1; p = 0.001) were related to RFS, and in OS, stage (HR, 5.4; p = 0.037), adjuvant treatment (HR, 8.6; p = 0.004), and beclin-1 expression (HR, 8.2; p = 0.011) were identified as significant prognostic factors. Conclusions: Our findings suggest that high beclin-1 expression predicts longer survival in locally advanced NSCLC and docetaxel-platinum IC is a treatment option that deserves consideration.
참고문헌 (26)
- Gilligan D, "Preoperative chemotherapy in patients with resectable non-small cell lung cancer : results of the MRC LU22", NVALT 2, Lancet, pp.2007, 369[DOI]
- Song WA, "Survival benefit of neoadjuvant chemotherapy in non-small cell lung cancer : an updated meta-analysis of 13 randomized control trials", J Thorac Oncol, 5, pp.510~516 (2010)
- Besse B, "ERCC1 and RRM1: ready for prime time?", J Clin Oncol, 31, pp.1050~1060 (2013)
- Olaussen KA, "DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy", N Engl J Med, 355, pp.983~991 (2006)
- Wachters FM, "ERCC1, hRad51, and BRCA1 protein expression in relation to tumour response and survival of stage III", IV NSCLC patients treated with chemotherapy, 2005, pp.50, 211~219
- Lee AS, "GRP78 induction in cancer : therapeutic and prognostic implications", Cancer Res, 67, pp.3496~3499 (2007)
- Pyrko P, "The unfolded protein response regulator GRP78", BiP as a novel target for increasing chemosensitivity in malignant gliomas, 2007, pp.67, 9809~9816
- Wirawan E, "Beclin1 : a role in membrane dynamics and beyond", Autophagy, 8, pp.6~17 (2012)
- White E, "The double-edged sword of autophagy modulation in cancer", Clin Cancer Res, 15, pp.5308~5316 (2009)
- Morselli E, "Anti-and pro-tumor functions of autophagy", Biochim Biophys Acta, 1793, pp.1524~1532 (2009)
- Chen K, "Autophagy regulates resistance of nonsmall cell lung cancer cells to paclitaxel", Tumour Biol, 37, pp.10539~10544 (2016)
- Wang X, "Beclin 1 and p62 expression in non-small cell lung cancer : relation with malignant behaviors and clinical outcome", Int J Clin Exp Pathol, 8, pp.10644~10652 (2015)
- Pan B, "HMGB1-mediated autophagy promotes docetaxel resistance in human lung adenocarcinoma", Mol Cancer, 13, pp.165~ (2014)
- Aita VM, "Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21", Genomics, 59, pp.59~65 (1999)
- Zhu W, "Expression of Beclin 1 and LC3 in FIGO stage I-II cervical squamous cell carcinoma and relationship to survival", Tumour Biol, 33, pp.1653~1659 (2012)
- Wu XY, "Beclin 1 activation enhances chemosensitivity and predicts a favorable outcome for primary duodenal adenocarcinoma", Tumour Biol, 34, pp.713~722 (2013)
- Veldhoen RA, "The chemotherapeutic agent paclitaxel inhibits autophagy through two distinct mechanisms that regulate apoptosis", Oncogene, 32, pp.736~746 (2013)
- Ko YH, "Prognostic significance of autophagy-related protein expression in resected pancreatic ductal adenocarcinoma", Pancreas, 42, pp.829~835 (2013)
- Giatromanolaki A, "High Beclin 1 expression defines a poor prognosis in endometrial adenocarcinomas", Gynecol Oncol, 123, pp.147~151 (2011)
- Kim KM, "Expression of ER stress and autophagy-related molecules in human non-small cell lung cancer and premalignant lesions", Int J Cancer, 131, pp.E362~E370 (2012)
- Sun Q, "Expressions of GRP78 and Bax associate with differentiation, metastasis, and apoptosis in non-small cell lung cancer", Mol Biol Rep, 39, pp.6753~6761 (2012)
- Friboulet L, "ERCC1 isoform expression and DNA repair in non-small-cell lung cancer", N Engl J Med, 368, pp.1101~1110 (2013)
- Felip E, "Preoperative chemotherapy plus surgery versus surgery plus adjuvant chemotherapy versus surgery alone in early-stage non-small-cell lung cancer", J Clin Oncol, 28, pp.3138~3145 (2010)
- Pisters KM, "Surgery with or without preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer : Southwest Oncology Group Trial S9900, an intergroup, randomized, phase III trial", J Clin Oncol, 28, pp.1843~1849 (2010)
- Scagliotti GV, "Randomized phase III study of surgery alone or surgery plus preoperative cisplatin and gemcitabine in stages IB to IIIA non-small-cell lung cancer", J Clin Oncol, 30, pp.172~178 (2012)
- Berman AT, "Immunotherapy in locally-advanced non-small cell lung cancer: releasing the brakes on consolidation?", Transl Lung Cancer Res, 5, pp.138~142 (2016)