ORIGINAL RESEARCH ARTICLE
Expression of Caspase-9 in Early and Locally Advanced Stage Squamous Cell Lung Cancer
Received Date : 31 May 2020
Accepted Date : 02 Sep 2020
Available Online : 29 Sep 2020
Burcu YAPAR TAŞKÖYLÜa, Aydın DEMİRAYb, Atike Gökçen DEMİRAYa, Gamze GÖKÖZ DOĞUa, Arzu YARENa, Serkan DEĞİRMENCİOĞLUa, Nail ÖZHANc, Canan KARANa, Umut ÇAKIROĞLUd, Hakan AKÇAb, Ferda BİRe, Ahmet ERGİNf
aDepartment of Medical Oncology, Pamukkale University Faculty of Medicine, Denizli, TURKEY
bDepartment of Medical Biology, Pamukkale University Faculty of Medicine, Denizli, TURKEY
cClinic of Medical Oncology, Kayseri City Hospital, Kayseri, TURKEY
dClinic of Medical Oncology, Van Training and Research Hospital, Van, TURKEY
eDepartment of Pathology, Pamukkale University Faculty of Medicine, Denizli, TURKEY
fDepartment of Social Pediatrics, Pamukkale University Faculty of Medicine, Denizli, TURKEY
Doi: 10.37047/jos.2020-76948 - Article's Language: EN
J Oncol Sci. 2020;6(3):147-52
ABSTRACT
Objective:Apoptosis plays a critical role in carcinogenesis. Intracellular proteases known as caspase-9 directly or indirectly play
roles inactivating apoptosis. In this study, we aimed to investigate the effect of caspase-9 level in lung skuamous cancer tumor tissues on lymph
node metastasis, clinicopathologic parameters and prognosis. Material and Methods: The study included 50 patients diagnosed with squamous
cell lung cancer. The caspase-9 level in the tumor and metastatic lymph nodes was assessed using real time-polymerase chain reaction(
RT-PCR) methods. Results: The median age of the patients was 61 years (range, 54-68 years). All patients were men and smokers. The
average duration of follow-up was 50.26±39.21 months, and progression-free survival was 26.34±19.50 months. Among 50 patients, 22 (44%)
had lymph node metastasis. The caspase-9 level was studied in tumors with and without lymph node metastasis. Moreover, the caspase-9 levels
in tumors with lymph node metastasis were statistically and significantly lower than tumors without lymph node metastasis (p<0.001). The
caspase-9 level decreased as the stage increased (p<0.001). In the presence of angiolymphatic invasion and poorly differentiated tumor tissue,
a low level of caspase-9 was identified. Conclusion: The caspase-9 level decreased with increasing stage and the presence of lymph
node metastasis. No statistically significant association was detected between caspase-9 and survival. A literature review revealed that no
studies have evaluated the correlation between caspase-9 in the squamous cell subtype, clinicopathological parameters, and survival. Extensive
studies involving a significant number of patients are required to determine the prognostic and predictive significance of the caspase-9
level in our population.
Keywords: Lung neoplasm; apoptosis; caspase 9
REFERENCES
- Torre LA, Siegel RL, Jemal A. Lung cancer statistics. AdvExp Med Biol. 2016;893:1-19. [Crossref] [PubMed]
- Noone AM, Howlader N, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2015.
- Bratton SB, Salvesen GS. Regulation of the Apaf-1- caspase-9 apoptosome. Journal of Cell Science. 2010;123:3209-14. [Crossref] [PubMed] [PMC]
- Adams JM, Cory S. Life or death decisions by the Bcl-2 family. Trends. BiochemSci. January 2001;26:61-6. [Crossref] [PubMed]
- Hu Q, Wu D, Chen W, Yan Z, Yan C, He T, Liang Q, Shi Y. Molecular determinants of caspase-9 activation by the Apaf-1 apoptosome. Proceedings of the National Academy of Sciences of the United States of America. November 2014;111:16254-61. [Crossref] [PubMed] [PMC]
- Boatright KM, Salvesen GS. Mechanisms of caspase activation. Curr Opin Cell Biol. 2003;15(6):725-31. [Crossref] [PubMed]
- Li P, Zhou L, Zhao T, Liu X, Zhang P, Liu Y, X Zheng X, Q Li.Caspase-9: structure, mechanisms and clinical application.Oncotarget. 2017;8(14):23996-4008. [Crossref] [PubMed] [PMC]
- Shultz JC, Goethe RW, Murudkar CS, Wijesinghe DS, Mayton EK, Massiello A, et al. srsf1 regulates the alternative splicing of caspase 9 via a novel ıntronic splicing enhancer. affecting the chemotherapeuticsensitivity of non-small cell lungcancercells. Mol Cancer Res. 2011;9(7):889-900. [Crossref] [PubMed] [PMC]
- Straathof KC, Pulè MA, Yotnda P, Dotti G, Vanin EF, Brenner MK, et al. An inducible caspase 9 safety switch for T-cell therapy. Blood. 2005;105(11):4247-54. [Crossref] [PubMed] [PMC]
- Murray TV, McMahon JM, Howley BA, Stanley A, Ritter T, Mohr A, et al. A non-apoptotic role for caspase-9 in muscle differentiation. J Cell Sci. 2008;121(pt 22):3786-93. [Crossref] [PubMed]
- D'Sa-Eipper C, Leonard JR, Putcha G, Zheng TS, Flavell RA, Rakic P, et al. DNA damage-induced neural precursor cell apoptosis requires p53 and caspase 9 but neither Bax nor caspase 3. Development. 2001;128(1):137-46. [PubMed]
- Ercan S, Arinc S, Yilmaz SG, Altunok C, Yaman F, Isbir T. Investigation of caspase 9 gene polymorphism in patients with non-small cell lung cancer. Anticancer Res. 2019;39(5):2437-41. [Crossref] [PubMed]
- Yilmaz SG, Yencilek F, Yildirim A, Yencilek E, Isbir T.Effects of caspase 9 gene polymorphism in patients with prostate cancer. In Vivo. 2017;31(2):205-8. [Crossref] [PubMed] [PMC]
- Shen XG, Wang C, Li Y, Wang L, Zhou B, Xu B, Jiang X, et al. Downregulation of caspase-9 is a frequent event in patients with stage II colorectal cancer and correlates with poor clinical outcome. ColorectalDis. 2010;12(12):1213-8. [Crossref] [PubMed]
- Park JY, Park JM, Jang JS, Choi JE, Kim KM, Cha SI, Kim CHet al. Caspase 9 promoter polymorphisms and risk of primary lung cancer.Hum Mol Genet. 2006;15(12):1963-71. [Crossref] [PubMed]
- Xu W, Jiang S, Xu Y, Chen B, Li Y, Zong F, Zhao W, Wu J. A meta-analysis of caspase 9 polymorphisms in promoter and exon sequence on cancer susceptibility. PLoS One. 2012;7(5):e37443. [Crossref] [PubMed] [PMC]
- Asadi M, Shanehbandi D, Asvadi Kermani T, Sanaat Z, Zafari V, Hashemzadeh S. Expression level of caspase genes in colorectal cancer. Asian Pac J Cancer Prev. 2018;19(5):1277-80. [Crossref] [PubMed] [PMC]
- Theodoropoulos GE, Michalopoulos NV, Pantou MP, Kontogianni P, Gazouli M, Karantanos T, et al. Caspase 9 promoter polymorphisms confer increased susceptibility to breast cancer. Cancer Genet. 2012;205(10):508-12. [Crossref] [PubMed]
- Zhang L, Zhang X, Wang X, He M, Qiao S. MicroRNA-224 Promotes tumorigenesis through downregulation of caspase-9 in triple-negative breast cancer. Dis Markers. February 2019;2019:7378967. [Crossref] [PubMed] [PMC]
- Ozdogan S, Kafadar A, Yilmaz SG, Timirci-Kahraman O, Gormus U, Isbir T. Role of caspase-9 Gene Ex5+32 G>A [rs1052576] variant in susceptibility to primary brain tumors. Anticancer Res. 2017;37(9):4997-5000. [Crossref] [PubMed]
- Marques I, Teixeira AL, Ferreira M, Assis J, Lobo F, Maurício J, et al. Influence of survivin [BIRC5] and caspase-9 [CASP9] functional polymorphisms in renal cell carcinoma development: a study in a southern European population. Mol Biol Rep. 2013;40(8):4819-26. [Crossref] [PubMed]
- Sharifi S, Barar J, Hejazi MS, Samadi N. Roles of the Bcl-2/Bax ratio, caspase-8 and 9 in resistance of breast cancer cells to paclitaxel. Asian Pac J Cancer Prev. 2014;15(20):8617-22. [PubMed]
- Kuwahara D, Tsutsumi K, Kobayashi T, Hyoudou M, Koizuka I. Inhibition of caspase-9 activity in cisplatin-resistant head and neck squamous cell carcinoma. Nihon Jibiinkoka Gakkai Kaiho. 2002;105(2):152-7. [Crossref] [PubMed]
- Kemper K, Rodermond H, Colak S, Grandela C, Medema JP.Targeting colorectal cancer stem cells with inducible caspase-9. Apoptosis. 2012;17(5):528-37. [Crossref] [PubMed] [PMC]
- Iwai N, Yasui K, Tomie A, Gen Y, Terasaki K, Kitaichi T, et al. Oncogenic miR-96-5p inhibits apoptosis by targeting the caspase-9 gene in hepatocellular carcinoma. Int J Oncol. 2018;53(1):237-45. [Crossref] [PubMed] [PMC]
- Sträter J, Herter I, Merkel G, Hinz U, Weitz J, Möller P. Expression and prognosticsignificance of APAF-1, caspase-8 and caspase-9 in stage II/III colon carcinoma: caspase-8 and caspase-9 is associated with poorprognosis. Int J Cancer. 2010;127(4):873-80. [Crossref] [PubMed]
- Terlizzi M, Colarusso C, De Rosa I, De Rosa N, Somma P, Curcio C, et al. Circulating and tumor-associated caspase-4: a novel diagnostic and prognostic biomarker for non-small cell lung cancer. Oncotarget. 2018;9(27):19356-67. [Crossref] [PubMed] [PMC]
- Liu D, Xu W, Ding X, Yang Y, Lu Y, Fei K, et al. Caspase 8 polymorphisms contribute to the prognosis of advanced lung adenocarcinoma patients after platinum-based chemotherapy. Cancer Biol Ther. 2017;18(12):948-57. [Crossref] [PubMed] [PMC]
- Theodoropoulos GE, Gazouli M, Vaiopoulou A, Leandrou M, Nikouli S, Vassou E, et al. Polymorphisms of caspase 8 and caspase 9 gene and colorectal cancer susceptibility and prognosis. Int J Colorectal Dis. 2011;26(9):1113-8. [Crossref] [PubMed]