Mối liên hệ giữa các biến thể nucleotide đơn ở gen E2F1 và E2F2 với các đặc điểm giải phẫu bệnh của ung thư tế bào vảy thanh quản

BMC Cancer
Tomas Jakštas1, Agnė Bartnykaitė2, Evaldas Padervinskis1, Aurelija Vegienė1, Elona Juozaitytė3, Virgilijus Uloza1, Rasa Ugenskienė4
1Department of Otorhinolaryngology, Lithuanian University of Health Sciences, Kaunas, Lithuania
2Oncology Research Laboratory, Oncology Institute, Lithuanian University of Health Sciences, Kaunas, Lithuania
3Oncology Institute, Lithuanian University of Health Sciences, Kaunas, Lithuania
4Department of Genetics and Molecular Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania

Tóm tắt

Tóm tắt Nền tảng Ung thư tế bào vảy thanh quản (LSCC) là một trong những loại ung thư phổ biến nhất ở đường hô hấp trên. Nó được biết đến với tỷ lệ tử vong cao và tiên lượng kém ở giai đoạn muộn. Có những yếu tố nguy cơ đã được biết đến đối với LSCC, tuy nhiên, việc tìm kiếm các dấu ấn sinh học tiên lượng và cụ thể trong máu cho sự phát triển và tiên lượng của LSCC là rất cần thiết. Nghiên cứu hiện tại nhằm đánh giá ảnh hưởng của bốn biến thể nucleotide đơn (SNPs), E2F1 (rs3213183 và rs3213180) và E2F2 (rs2075993 và rs3820028), đến sự phát triển của LSCC, các đặc điểm hình thái và tỷ lệ sống sót sau 5 năm của bệnh nhân. Phương pháp Tổng cộng có 200 bệnh nhân LSCC và 200 đối tượng chứng được bao gồm trong nghiên cứu này; cả hai nhóm được ghép nối theo tuổi và giới tính. Trong nghiên cứu hiện tại, chúng tôi đã phân tích bốn biến thể nucleotide đơn (SNPs) trong các gen E2F1 (rs3213183 và rs3213180) và E2F2 (rs2075993 và rs3820028) và đánh giá mối liên hệ của chúng với nguy cơ phát triển LSCC, biểu hiện lâm sàng và hình thái, cũng như tỷ lệ sống sót sau 5 năm của bệnh nhân. Genotyping được thực hiện bằng RT-PCR. Kết quả Không có SNP nào trong số được phân tích cho thấy mối liên hệ trực tiếp với sự phát triển của LSCC. Những người mang allele G của E2F2 rs2075993 (OR = 4.589, 95% CI 1.050-20.051, p = 0.043) và những người mang allele A của rs3820028 (OR = 4.750, 95% CI 1.088–20.736, p = 0.038) có nguy cơ cao hơn một cách có ý nghĩa thống kê đối với các dạng LSCC biệt hóa kém hoặc không biệt hóa hơn so với những người không mang allele. Những người đồng hợp tử GC của E2F1 rs3213180 được phát hiện có nguy cơ cao hơn 3.7 lần đối với sự liên quan của lympho (OR = 3.710, 95% CI 1.452–9.479, p = 0.006). Không có mối liên hệ đáng kể nào giữa các SNP được điều tra và tỷ lệ sống sót sau 5 năm của bệnh nhân. Kết luận Nghiên cứu hiện tại chỉ ra rằng E2F2 rs2075993 và rs3820028 ảnh hưởng đến sự biệt hóa của LSCC, trong khi E2F1 rs3213180 ảnh hưởng đến sự liên quan của hạch bạch huyết.

Từ khóa


Tài liệu tham khảo

World Health Organization. Cancer Tomorrow. 2020 [cited 2023 Feb 23]. Available from: https://gco.iarc.fr/today/data/factsheets/cancers/14-Larynx-fact-sheet.pdf.

World Health Organization, International Agency for Research on Cancer. Estimated number of deaths from 2020 to 2040, both sexes, age (0–85+), 2020. [cited 2023 Feb 20]. Available from: https://gco.iarc.fr/tomorrow/en/dataviz/bubbles?sexes=0&mode=population&group_populations=0&multiple_cancers=1&cancers=39_14&group_cancers=1.

Di Credico G, Polesel J, Dal Maso L, Pauli F, Torelli N, Luce D, et al. Alcohol drinking and head and neck cancer risk: the joint effect of intensity and duration. Br J Cancer. 2020;123(9):1456–63. https://doi.org/10.1038/s41416-020-01031-z. Epub 2020 Aug 24. PMID: 32830199; PMCID: PMC7592048.

Sterba KR, Garrett-Mayer E, Carpenter MJ, Tooze JA, Hatcher JL, Sullivan C, et al. Smoking status and symptom burden in surgical head and neck cancer patients. Laryngoscope. 2017;127(1):127–33. https://doi.org/10.1002/lary.26159. Epub 2016 Jul 9. PMID: 27392821; PMCID: PMC5177454.

Ramsey T, Guo E, Svider PF, Lin H, Syeda S, Raza SN, et al. Laryngeal cancer: global socioeconomic trends in disease burden and smoking habits. Laryngoscope. 2018;128(9):2039–53. https://doi.org/10.1002/lary.27068. Epub 2018 Mar 6. PMID: 29508408.

Maasland DH, van den Brandt PA, Kremer B, Goldbohm RA, Schouten LJ. Alcohol consumption, cigarette smoking and the risk of subtypes of head-neck cancer: results from the Netherlands Cohort Study. BMC Cancer. 2014;14:187. https://doi.org/10.1186/1471-2407-14-187. PMID: 24629046; PMCID: PMC4004328.

Cornean CI, Cosgarea M, Cătană A, Mogoantă CA, Necula V, Maniu AA. Do we know enough about the genetic involvement in laryngeal cancer susceptibility and prognostic outcome? Rom J Morphol Embryol. 2019;60(2):353–67. PMID: 31658308.

Uloza V, Tamauskaite T, Vilkeviciute A, Pasvenskaite A, Liutkevicius V, Liutkeviciene R. Determination of SIRT1 rs12778366, FGFR2rs2981582, STAT3 rs744166, and RAGErs1800625 Single Gene Polymorphisms in Patients with Laryngeal Squamous Cell Carcinoma. Dis Markers. 2019; 2019:3907232. https://doi.org/10.1155/2019/3907232. PMID: 31781300; PMCID: PMC6875326.

Vaiciulis P, Liutkeviciene R, Liutkevicius V, Vilkeviciute A, Gedvilaite G, Uloza V. Association of SIRT1 single gene nucleotide polymorphisms and serum SIRT1 levels with laryngeal squamous cell carcinoma patient survival rate. Cancer Biomark. 2022;34(2):175–88. https://doi.org/10.3233/CBM-210264. PMID: 34719479; PMCID: PMC9198736.

Insodaite R, Liutkevicius V, Uloza V, Solovejute R, Smalinskiene A. Association Between MMP8 Gene Polymorphisms and Laryngeal Squamous Cell Carcinoma. Anticancer Res. 2020;40(4):2003–2009. https://doi.org/10.21873/anticanres.14156. PMID: 32234890.

Polager S, Ginsberg D. p53 and E2f: partners in life and death. Nat Rev Cancer. 2009;9(10):738– 48. https://doi.org/10.1038/nrc2718. PMID: 19776743.

Polager S, Ginsberg D. E2F - at the crossroads of life and death. Trends Cell Biol. 2008;18(11):528–35. https://doi.org/10.1016/j.tcb.2008.08.003. Epub 2008 Sep 18. PMID: 18805009.

Zheng X, Huang M, Xing L, Yang R, Wang X, Jiang R, et al. The circRNA circSEPT9 mediated by E2F1 and EIF4A3 facilitates the carcinogenesis and development of triple-negative breast cancer. Mol Cancer. 2020;19(1):73. https://doi.org/10.1186/s12943-020-01183-9. PMID: 32264877; PMCID: PMC7137343.

Lin X, Han T, Xia Q, Cui J, Zhuo M, Liang Y, et al. CHPF promotes gastric cancer tumorigenesis through the activation of E2F1. Cell Death Dis. 2021;12(10):876. https://doi.org/10.1038/s41419-021-04148-y. PMID: 34564711; PMCID: PMC8464597.

Jing Z, Liu Q, He X, Jia Z, Xu Z, Yang B, et al. NCAPD3 enhances Warburg effect through c-myc and E2F1 and promotes the occurrence and progression of colorectal cancer. J Exp Clin Cancer Res. 2022;41(1):198. https://doi.org/10.1186/s13046-022-02412-3. PMID: 35689245; PMCID: PMC9188166.

Shang Y, Zhang Y, Liu J, Chen L, Yang X, Zhu Z, et al. Decreased E2F2 expression correlates with poor prognosis and Immune infiltrates in patients with colorectal Cancer. J Cancer. 2022;13(2):653–68. https://doi.org/10.7150/jca.61415. PMID: 35069909; PMCID: PMC8771517.

Chen L, Yu JH, Lu ZH, Zhang W. E2F2 induction in related to cell proliferation and poor prognosis in non-small cell lung carcinoma. Int J Clin Exp Pathol. 2015;8(9):10545–54. PMID: 26617764; PMCID: PMC4637579.

Li H, Guo J, Cheng G, Wei Y, Liu S, Qi Y, et al. Identification and validation of SNP-Containing genes with Prognostic Value in Gastric Cancer via Integrated Bioinformatics Analysis. Front Oncol. 2021;11:564296. https://doi.org/10.3389/fonc.2021.564296. PMID: 33987081; PMCID: PMC8112818.

Lu M, Liu Z, Yu H, Wang LE, Li G, Sturgis EM, et al. Combined effects of E2F1 and E2F2 polymorphisms on risk and early onset of squamous cell carcinoma of the head and neck. Mol Carcinog. 2012;51(Suppl 1):E132–41. https://doi.org/10.1002/mc.21882. Epub 2012 Feb 17. PMID: 22344756; PMCID: PMC3370129.

Li Y, Sturgis EM, Zhu L, Cao X, Wei Q, Zhang H, et al. E2F transcription factor 2 variants as predictive biomarkers for recurrence risk in patients with squamous cell carcinoma of the oropharynx. Mol Carcinog. 2017;56(4):1335–43. https://doi.org/10.1002/mc.22595. Epub 2017 Jan 2. PMID: 27864908; PMCID: PMC6036627.

Gingerich MA, Smith JD, Michmerhuizen NL, Ludwig M, Devenport S, Matovina C, et al. Comprehensive review of genetic factors contributing to head and neck squamous cell carcinoma development in low-risk, nontraditional patients. Head Neck. 2018;40(5):943–54. https://doi.org/10.1002/hed.25057. Epub 2018 Feb 10. PMID: 29427520; PMCID: PMC5912962.

Pfister DG, Spencer S, Adelstein D, Adkins D, Anzai Y, Brizel DM et al. Head and Neck Cancers, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2020;18(7):873–898. https://doi.org/10.6004/jnccn.2020.0031. PMID: 32634781.

Yang T, Li S, Liu J, Yin D, Yang X, Tang Q. lncRNA-NKILA/NF-κB feedback loop modulates laryngeal cancer cell proliferation, invasion, and radioresistance. Cancer Med. 2018;7(5):2048–63. https://doi.org/10.1002/cam4.1405. Epub 2018 Mar 23. PMID: 29573243; PMCID: PMC5943486.

Révész M, Oberna F, Slezák A, Ferenczi Ö, Kenessey I, Takácsi-Nagy Z. The characteristics of head and neck squamous cell cancer in young adults: a retrospective single-center study. Pathol Oncol Res. 2023;29:1611123. https://doi.org/10.3389/pore.2023.1611123. PMID: 37168050; PMCID: PMC10164923.

Ursu RG, Luchian I, Damian C, Porumb-Andrese E, Ghetu N, Cobzaru RG, et al. Diagnostics of HNSCC patients: an analysis of cell lines and patient-derived xenograft models for personalized Therapeutical Medicine. Diagnostics (Basel). 2022;12(5):1071. https://doi.org/10.3390/diagnostics12051071. PMID: 35626227; PMCID: PMC9139588.

Yuan Y, Sturgis EM, Zhu L, Lu M, Li Y, Wei Q, et al. A functional variant at the miRNA binding site in E2F1 gene is associated with risk and tumor HPV16 status of oropharynx squamous cell carcinoma. Mol Carcinog. 2017;56(3):1100–6. Epub 2016 Oct 20. PMID: 27677255.

Contrera KJ, Hair BB, Prendes B, Reddy CA, Zimmer DI, Burkey BB, et al. Clinical Versus Pathologic Laryngeal Cancer Staging and the impact of Stage Change on outcomes. Laryngoscope. 2021;131(3):559–65. https://doi.org/10.1002/lary.28924. Epub 2020 Jul 21. PMID: 32692866.

Kent LN, Leone G. The broken cycle: E2F dysfunction in cancer. Nat Rev Cancer. 2019;19(6):326–338. https://doi.org/10.1038/s41568-019-0143-7. PMID: 31053804.

Wu T, Wu L. The role and clinical implications of the Retinoblastoma (RB)-E2F pathway in gastric Cancer. Front Oncol. 2021;11:655630. https://doi.org/10.3389/fonc.2021.655630. PMID: 34136392; PMCID: PMC8201093.

Chen M, Xu WM, Wang GY, Hou YX, Tian TT, Li YQ et al. Genetic variants of cell cycle pathway genes are associated with head and neck squamous cell carcinoma in the Chinese population. Carcinogenesis. 2021;42(11):1337–1346. https://doi.org/10.1093/carcin/bgab094. PMID: 34643214.

Kassab A, Gupta I, Moustafa AA. Role of E2F transcription factor in oral cancer: recent insight and advancements. Semin Cancer Biol. 2023;92:28–41. https://doi.org/10.1016/j.semcancer.2023.03.004. Epub 2023 Mar 15. PMID: 36924812.

Song L, Li H, Ma RR, Liu S, Zhang GH, Guo XY, et al. E2F1-initiated transcription of PRSS22 promotes breast cancer metastasis by cleaving ANXA1 and activating FPR2/ERK signaling pathway. Cell Death Dis. 2022;13(11):982. https://doi.org/10.1038/s41419-022-05414-3. PMID: 36414640; PMCID: PMC9681780.

Fang Z, Lin M, Li C, Liu H, Gong C. A comprehensive review of the roles of E2F1 in colon cancer. Am J Cancer Res. 2020;10(3):757–68. PMID: 32266089; PMCID: PMC7136928.

Xu Z, Qu H, Ren Y, Gong Z, Ri HJ, Chen X. An update on the potential roles of E2F family members in Colorectal Cancer. Cancer Manag Res. 2021;13:5509–21. PMID: 34276228; PMCID: PMC8277564.

Li H, Zhao S, Shen L, Wang P, Liu S, Ma Y, et al. E2F2 inhibition induces autophagy via the PI3K/Akt/mTOR pathway in gastric cancer. Aging. 2021;13(10):13626–43. https://doi.org/10.18632/aging.202891. Epub 2021 Apr 21. PMID: 34091441; PMCID: PMC8202834.

Xie L, Li T, Yang LH. E2F2 induces MCM4, CCNE2 and WHSC1 upregulation in ovarian cancer and predicts poor overall survival. Eur Rev Med Pharmacol Sci. 2017;21(9):2150–6. PMID: 28537669.

Deng N, Zhou H, Fan H, Yuan Y. Single nucleotide polymorphisms and cancer susceptibility. Oncotarget. 2017;8(66):110635–49. https://doi.org/10.18632/oncotarget.22372. PMID: 29299175; PMCID: PMC5746410.

Ozturk K, Onal MS, Efiloglu O, Nikerel E, Yildirim A, Telci D. Association of 5’UTR polymorphism of secretory phospholipase A2 group IIA (PLA2G2A) gene with prostate cancer metastasis. Gene. 2020;742:144589. https://doi.org/10.1016/j.gene.2020.144589. Epub 2020 Mar 13. PMID: 32179174.

Steuer CE, El-Deiry M, Parks JR, Higgins KA, Saba NF. An update on larynx cancer. CA Cancer J Clin. 2017;67(1):31–50. Epub 2016 Nov 29. PMID: 27898173.

Loyo M, Pai SI. The molecular genetics of laryngeal cancer. Otolaryngol Clin North Am. 2008;41(4):657– 72, v. https://doi.org/10.1016/j.otc.2008.01.019. PMID: 18570952.

Liberale C, Soloperto D, Marchioni A, Monzani D, Sacchetto L. Updates on Larynx Cancer: risk factors and oncogenesis. Int J Mol Sci. 2023;24(16):12913. https://doi.org/10.3390/ijms241612913. PMID: 37629093; PMCID: PMC10454133.

Sánchez-Siles M, Pelegrín-Hernández JP, Hellin-Meseguer D, Guerrero-Sánchez Y, Corno-Caparrós A, Cabezas-Herrera, et al. Genotype of null polymorphisms in genes GSTM1, GSTT1, CYP1A1, and CYP1A1*2A (rs4646903 T > C)/CYP1A1*2 C (rs1048943 A > G) in patients with Larynx Cancer in Southeast Spain. Cancers (Basel). 2020;12(9):2478. https://doi.org/10.3390/cancers12092478. PMID: 32882964; PMCID: PMC7563952.

Yang Y, Zhou J, Wu H. Significance of Cytokeratin-1 single-nucleotide polymorphism and protein level in susceptibility to vocal leukoplakia and laryngeal squamous cell carcinoma. ORL J Otorhinolaryngol Relat Spec. 2019;81(2–3):121–9. Epub 2019 May 8. PMID: 31067553.

Pasvenskaite A, Vilkeviciute A, Liutkeviciene R, Gedvilaite G, Liutkevicius V, Uloza V. Associations of IL6 rs1800795, BLK rs13277113, TIMP3 rs9621532, IL1RL1 rs1041973 and IL1RAP rs4624606 single gene polymorphisms with laryngeal squamous cell carcinoma. Gene. 2020;747:144700. https://doi.org/10.1016/j.gene.2020.144700. Epub 2020 Apr 21. PMID: 32330537.

Liu H, Li G, Sturgis EM, Shete S, Dahlstrom KR, Du M, et al. Genetic variants in CYP2B6 and HSD17B12 associated with risk of squamous cell carcinoma of the head and neck. Int J Cancer. 2022;151(4):553–64. Epub 2022 May 7. PMID: 35404482; PMCID: PMC9203942.

Mosser DM, Zhang X. Interleukin-10: new perspectives on an old cytokine. Immunol Rev. 2008;226:205–18. https://doi.org/10.1111/j.1600-065X.2008.00706.x. PMID: 19161426; PMCID: PMC2724982.

Li Y, Huang Y, Li B, Yang K. Roles of E2F family members in the diagnosis and prognosis of head and neck squamous cell carcinoma. BMC Med Genomics. 2023;16(1):38. https://doi.org/10.1186/s12920-023-01470-6. PMID: 36855110; PMCID: PMC9976507.

Zhang Y, Li W, Wang Y, Wang N. The PLCE1 rs2274223 variant is associated with the risk of laryngeal squamous cell carcinoma. Int J Med Sci. 2020;17(17):2826–30. https://doi.org/10.7150/ijms.49012. PMID: 33162810; PMCID: PMC7645332.

Lehnerdt GF, Franz P, Winterhoff S, Bankfalvi A, Grehl S, Lang S et al. The GNAS1 T393C polymorphism predicts survival in patients with advanced squamous cell carcinoma of the larynx. Laryngoscope. 2008;118(12):2172-6. https://doi.org/10.1097/MLG.0b013e318185793ds. PMID: 19029852.

Almadori G, Bussu F, Cadoni G, Galli J, Paludetti G, Maurizi M. Molecular markers in laryngeal squamous cell carcinoma: towards an integrated clinicobiological approach. Eur J Cancer. 2005;41(5):683– 93. https://doi.org/10.1016/j.ejca.2004.10.031. PMID: 15763643.

Qu Y, Feng J, Wang L, Wang H, Liu H, Sun X, et al. Association between Head and Neck Cancers and polymorphisms 869T/C, 509 C/T, and 915G/C of the transforming growth Factor-β1 gene: a Meta-analysis of case-control studies. Med Sci Monit. 2019;25:8389–402. PMID: 31698408; PMCID: PMC6857353.

Vossen DM, Verhagen CVM, Verheij M, Wessels LFA, Vens C, van den Brekel MWM. Comparative genomic analysis of oral versus laryngeal and pharyngeal cancer. Oral Oncol. 2018;81:35–44. https://doi.org/10.1016/j.oraloncology.2018.04.006. Epub 2018 Apr 13. PMID: 29884412.

Cadoni G, Giraldi L, Petrelli L, Pandolfini M, Giuliani M, Paludetti G, et al. Prognostic factors in head and neck cancer: a 10-year retrospective analysis in a single-institution in Italy. Acta Otorhinolaryngol Ital. 2017;37(6):458–66. https://doi.org/10.14639/0392-100X-1246. PMID: 28663597; PMCID: PMC5782422.

Goel MK, Khanna P, Kishore J. Understanding survival analysis: Kaplan-Meier estimate. Int J Ayurveda Res. 2010;1(4):274–8. https://doi.org/10.4103/0974-7788.76794. PMID: 21455458; PMCID: PMC3059453.

Thông tin
Thông tin xuất bản

BMC Cancer

Thông tin tác giả