Apoptoz ilişkili PDCD4: Oral kanserin erken tanısında umut vaadedici yeni bir biyobelirteç

Year 2022, Volume: 11 Issue: 2, 150 - 156, 18.05.2022

Leyla Bozdağ , Leyla Açık , Halil Ersoy , Ömer Bayır , Mehmet Hakan Korkmaz , Nur Mollaoğlu , Sibel Elif Gültekin

https://doi.org/10.54617/adoklinikbilimler.1091916

Cited By: 1

Abstract

Amaç: Bu çalışma, oral potansiyel malign bozukluk (OPMD) ve oral skuamöz hücreli karsinom karsinomun (OSCC) ilerlemesinde rol oynayan PDCD4 geninin potansiyel rolünü araştırmayı amaçlamıştır.
Gereç ve Yöntem: Çalışma OSCC (n=6), OPMD (n=6) ve sağlıklı (n=6) bireylerden alınan tükürük ve kan örnekleri üzerinde gerçekleştirildi. PDCD4'ün ifadesi, qRT-PCR kullanılarak belirlendi. PDCD4 ekspresyonu ile OSCC ve OPMD hastalarının klinik özellikleri arasındaki ilişkiyi tahmin etmek için Kruskal Wallis testi yapıldı. PDCD4 ekspresyonu ile hasta gruplarının korelasyonu Rank Spearman testi ile test edildi.
Bulgular: PDCD4 mRNA ekspresyon seviyeleri 6 OSCC'de, 6 OPMD hastasında ve 6 sağlıklı bireyde tükürük ve kanda değerlendirildi. Hem kanda hem de tükürükte, PDCD4 mRNA ekspresyon seviyeleri OSCC'de 6/6 (%100) düşük ifade edilirken, OPMD'nin 5/6'sında (%83) düşük ifade edildi. Ortalama PDCD4 değeri, OPMD ve OSCC'de sağlıklı olandan önemli ölçüde düşük ifade edildi (p<0.05). Rank Spearman testi ile p= 0.024 (p < 0.05) OSCC ve OPMD arasında anlamlı bir korelasyon gösterirken; -0.530 korelasyon katsayısı, , PDCD4 ‘ün OPMD ve OSCC arasında güçlü bir negatif korelasyona sahip olduğunu gösterdi.
Sonuç: PDCD4 ekspresyon seviyesi, OSCC ve OPMD ile ilişkilidir. Bu çalışma, sıvı biyopsilerdeki PDCD4 ekspresyon seviyelerinin OSCC ve OPMD'de tanısal bir biyobelirteç olma potansiyeline sahip olabileceğini göstermektedir.

Keywords

Oral skuamöz hücreli karsinom, Oral potansiyel malign bozukluk, PDCD4, kan, tükürük

Supporting Institution

Gazi Üniversitesi Bilimsel Araştırmalar Projeleri Koordinasyon Birimi

Project Number

TDK-2021-6939

Apoptosis Related PDCD4: Promising Novel Biomarker Early Detection of Oral Cancer

Abstract

Aim: This study aimed to investigate the potential role of the PDCD4 gene, involved in the progression of the oral potentially malign disorder (OPMD) and oral squamous cell carcinoma cancer (OSCC).

Material and Methods: The study was conducted on saliva and blood samples that were collected from OSCC (n=6), OPMD (n=6) patients, and healthy (n=6) individuals. The expression of PDCD4 was determined by using qRT-PCR. Kruskal Wallis test was performed to estimate the relationship between PDCD4 expression and clinical characteristics of OSCC and OPMD patients. The correlation between PDCD4 expression and patients groups was tested with the Rank Spearman test.

Results: PDCD4 mRNA expression levels were assessed in 6 OSCCs, 6 OPMD patients, and 6 healthy individuals saliva and blood. In both blood and saliva, PDCD4 mRNA expression levels were 6/6 (100%) underexpressed in OSCC, while it was underexpressed in 5/6 (83%) of OPMD. The mean value of PDCD4 was significantly downregulated in OPMD and OSCC than in healthy (p<0.05). The Spearman rank test obtained a p-value for the 2 tail test of 0.024 (p < 0.05), which showed a significant correlation between both, while the correlation coefficient of -0.530 showed a strong negative correlation of PDCD4 downregülation and OPMD, OSCC.

Conclusion: PDCD4 expression level is correlated with OSCC and OPMD. This study indicates that PDCD4 expression levels in liquid biopsies may have potential as a diagnostic biomarker in OSCC and OPMD.

Keywords

Blood, Oral squamous cell carcinoma, Oral potentially malign disorder, saliva, pdcd4

Project Number

TDK-2021-6939

References

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49.
• Madhura MG, Rao RS, Patil S, Fageeh HN, Alhazmi A, Awan KH. Advanced diagnostic aids for oral cancer. Dis Mon. 2020;66(12):101034.
• Wang J, Chang S, Li G, Sun Y. Application of liquid biopsy in precision medicine: opportunities and challenges. Front Med. 2017;11(4):522-7.
• van Ginkel JH, Huibers MMH, van Es RJJ, de Bree R, Willems SM. Droplet digital PCR for detection and quantification of circulating tumor DNA in plasma of head and neck cancer patients. BMC Cancer. 2017;17(1):428.
• Braig F, Voigtlaender M, Schieferdecker A, Busch CJ, Laban S, Grob T, et al. Liquid biopsy monitoring uncovers acquired RAS-mediated resistance to cetuximab in a substantial proportion of patients with head and neck squamous cell carcinoma. Oncotarget. 2016;7(28):42988-95.
• Perdomo S, Avogbe PH, Foll M, Abedi-Ardekani B, Facciolla VL, Anantharaman D, et al. Circulating tumor DNA detection in head and neck cancer: evaluation of two different detection approaches. Oncotarget. 2017;8(42):72621-32.
• Mazurek AM, Rutkowski T, Fiszer-Kierzkowska A, Malusecka E, Skladowski K. Assessment of the total cfDNA and HPV16/18 detection in plasma samples of head and neck squamous cell carcinoma patients. Oral Oncol. 2016;54:36-41.
• Guo PT, Yang D, Sun Z, Xu HM. PDCD4 functions as a suppressor for pT2a and pT2b stage gastric cancer. Oncol Rep. 2013;29(3):1007-12.
• Jajoo S, Mukherjea D, Kaur T, Sheehan KE, Sheth S, Borse V, et al. Essential role of NADPH oxidase-dependent reactive oxygen species generation in regulating microRNA-21 expression and function in prostate cancer. Antioxid Redox Signal. 2013;19(16):1863-76.
• Ma G, Zhang H, Dong M, Zheng X, Ozaki I, Matsuhashi S, et al. Downregulation of programmed cell death 4 (PDCD4) in tumorigenesis and progression of human digestive tract cancers. Tumour Biol. 2013;34(6):3879-85.
• Zhen Y, Li D, Li W, Yao W, Wu A, Huang J, et al. Reduced PDCD4 Expression Promotes Cell Growth Through PI3K/Akt Signaling in Non-Small Cell Lung Cancer. Oncol Res. 2016;23(1-2):61-8.
• Kujan O, Khattab A, Oliver RJ, Roberts SA, Thakker N, Sloan P. Why oral histopathology suffers inter-observer variability on grading oral epithelial dysplasia: an attempt to understand the sources of variation. Oral Oncol. 2007;43(3):224-31.
• Navazesh M. Methods for collecting saliva. Ann N Y Acad Sci. 1993;694:72-7.
• Hilliard A, Hilliard B, Zheng SJ, Sun H, Miwa T, Song W, et al. Translational regulation of autoimmune inflammation and lymphoma genesis by programmed cell death 4. J Immunol. 2006;177(11):8095-102.
• Chen Y, Knosel T, Kristiansen G, Pietas A, Garber ME, Matsuhashi S, et al. Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis. J Pathol. 2003;200(5):640-6.
• Cervigne NK, Reis PP, Machado J, Sadikovic B, Bradley G, Galloni NN, et al. Identification of a microRNA signature associated with progression of leukoplakia to oral carcinoma. Hum Mol Genet. 2009;18(24):4818-29.
• Mudduluru G, Medved F, Grobholz R, Jost C, Gruber A, Leupold JH, et al. Loss of programmed cell death 4 expression marks adenoma-carcinoma transition, correlates inversely with phosphorylated protein kinase B, and is an independent prognostic factor in resected colorectal cancer. Cancer. 2007;110(8):1697-707.
• Wang Q, Sun Z, Yang HS. Downregulation of tumor suppressor Pdcd4 promotes invasion and activates both beta-catenin/Tcf and AP-1-dependent transcription in colon carcinoma cells. Oncogene. 2008;27(11):1527-35.
• Wei NA, Liu SS, Leung TH, Tam KF, Liao XY, Cheung AN, et al. Loss of Programmed cell death 4 (Pdcd4) associates with the progression of ovarian cancer. Mol Cancer. 2009;8:70.
• Reis PP, Tomenson M, Cervigne NK, Machado J, Jurisica I, Pintilie M, et al. Programmed cell death 4 loss increases tumor cell invasion and is regulated by miR-21 in oral squamous cell carcinoma. Mol Cancer. 2010;9:238.
• Hiyoshi Y, Kamohara H, Karashima R, Sato N, Imamura Y, Nagai Y, et al. MicroRNA-21 regulates the proliferation and invasion in esophageal squamous cell carcinoma. Clin Cancer Res. 2009;15(6):1915-22.
• Liao J, Liu R, Shi YJ, Yin LH, Pu YP. Exosome-shuttling microRNA-21 promotes cell migration and invasion-targeting PDCD4 in esophageal cancer. Int J Oncol. 2016;48(6):2567-79.
• Liu C, Tong Z, Tan J, Xin Z, Wang Z, Tian L. MicroRNA-21-5p targeting PDCD4 suppresses apoptosis via regulating the PI3K/AKT/FOXO1 signaling pathway in tongue squamous cell carcinoma. Exp Ther Med. 2019;18(5):3543-51.
• Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 2008;27(15):2128-36.
• Ludwig K, Fassan M, Mescoli C, Pizzi M, Balistreri M, Albertoni L, et al. PDCD4/miR-21 dysregulation in inflammatory bowel disease-associated carcinogenesis. Virchows Arch. 2013;462(1):57-63.
• Lankat-Buttgereit B, Goke R. The tumour suppressor Pdcd4: recent advances in the elucidation of function and regulation. Biol Cell. 2009;101(6):309-17.
• LaRonde-LeBlanc N, Santhanam AN, Baker AR, Wlodawer A, Colburn NH. Structural basis for inhibition of translation by the tumor suppressor Pdcd4. Mol Cell Biol. 2007;27(1):147-56.
• Kang MJ, Ahn HS, Lee JY, Matsuhashi S, Park WY. Up-regulation of PDCD4 in senescent human diploid fibroblasts. Biochem Biophys Res Commun. 2002;293(1):617-21.
• Yang HS, Jansen AP, Komar AA, Zheng X, Merrick WC, Costes S, et al. The transformation suppressor Pdcd4 is a novel eukaryotic translation initiation factor 4A binding protein that inhibits translation. Mol Cell Biol. 2003;23(1):26-37.