Identification of Tumorigenic Markers in Head and Neck Cancer Patients, Exploring their Correlation with Tumor Aggressiveness
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Abstract
Background: Globally, head and neck cancer (HNC) considered the sixth most severe cancer associated with multiple risk factors. Due to lack of personalized therapies and undefined biomarkers, HNC shows low overall survival rate. Long non-coding RNA (LncRNA) helps to regulate multiple gene expressions in multiple biological responses. LncRNA tumor biomarkers stimulated tumor aggressiveness, cellular proliferation and inhibit apoptosis with poor prognosis. BLACAT-1, NEAT-1, HIF-1α, Caspase-3, Caspase-9 and Telomerase were associated with metastasis, tumor staging (TNM stage) activated proliferation, invasion and migration.
Objective: The presented study aims to analyze tumorigenic biomarkers, (BLACAT-1, NEAT-1 and HIF-1α, Caspase-3, Caspase-9 and Telomerase) in development and progression of head and neck cancer. Meanwhile, to observe the correlation between these biomarkers in promoting head and neck cancer.
Methods: In this comprehensive study, EDTA blood samples (5ml each) were collected from a cohort comprising 50 head and neck cancer (HNC) patients and an additional 30 healthy controls. The primary objective was to extract RNA from these samples for a detailed analysis. The study focused on evaluating the correlation between various tumor biomarkers across different HNC tumor subtypes. This correlation was meticulously analyzed using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR), a method known for its precision in quantifying gene expression levels.
Results: BLACAT-1 shows a significant increase expression in squamous cell carcinoma. NEAT-1, Caspase-3 and Caspase-9 are non-significant in HNC tumor types whereas, inverse correlation was observed between NEAT-1 with Caspase-9 and direct proportion between NEAT-1 with Caspase-3. However, HIF-1α represented an insignificant data among all tumor subtypes under hypoxic microenvironment.
Conclusion: Higher expression levels are suggesting potential biomarkers, therefore a gene signature can be developed for determining the severity of breast tumor; therefore, can be exploited as novel therapeutic approaches to block tumor metastasis and angiogenesis.
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References
Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 2020 Nov 26;6(1):92.
pstein JB, Wilkie DJ, Fischer DJ, Kim YO, Villines D. Neuropathic and nociceptive pain in head and neck cancer patients receiving radiation therapy. Head Neck Oncol. 2009 Jul 14;1:26.
Barth DA, Prinz F, Teppan J, Jonas K, Klec C, Pichler M. Long-Noncoding RNA (lncRNA) in the Regulation of Hypoxia-Inducible Factor (HIF) in Cancer. Noncoding RNA. 2020 Jul 6;6(3):27.
Ye T, Yang X, Liu H, Lv P, Ye Z. Long Non-Coding RNA BLACAT1 in Human Cancers. Onco Targets Ther. 2020 Aug 20;13:8263-8272.
Zhu, Min et al. “Long non-coding RNA BLACAT1, a novel promising biomarker and regulator of human cancers.” Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie vol. 132 (2020): 110808.
Kozłowska J, Kozioł K, Stasiak M, Obacz J, Guglas K, Poter P, Mackiewicz A, Kolenda T. The role of NEAT1 lncRNA in squamous cell carcinoma of the head and neck is still difficult to define. Contemp Oncol (Pozn). 2020;24(2):96-105.
Ghafouri-Fard, Soudeh, and Mohammad Taheri. “Nuclear Enriched Abundant Transcript 1 (NEAT1): A long non-coding RNA with diverse functions in tumorigenesis.” Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie vol. 111 (2019): 51-59.
Zheng, Xiaofeng et al. “Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer.” Nature vol. 527,7579 (2015): 525-530.
Ziello JE, Jovin IS, Huang Y. Hypoxia-Inducible Factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia. Yale J Biol Med. 2007 Jun;80(2):51-60.
Shafique S, Haseeb HM, Bano K, Arshad A. Investigating Entosis and Autophagy Dynamics in Diverse Tumor Microenvironments , Pak-Euro Journal of Medical and Life Sciences: Vol. 7, 3 (2023) Dec: 219-226.
Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, Newmeyer DD, Wang HG, Reed JC, Nicholson DW, Alnemri ES, Green DR, Martin SJ. Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner. J Cell Biol. 1999 Jan 25;144(2):281-92.
Sanders EJ, Parker E. The role of mitochondria, cytochrome c and caspase-9 in embryonic lens fibre cell denucleation. J Anat. 2002 Aug;201(2):121-35.
Dratwa M, Wysoczańska B, Łacina P, Kubik T, Bogunia-Kubik K. TERT-Regulation and Roles in Cancer Formation. Front Immunol. 2020 Nov 19;11:589929.
Heeren AM, Punt S, Bleeker MC, Gaarenstroom KN, van der Velden J, Kenter GG, de Gruijl TD, Jordanova ES. Prognostic effect of different PD-L1 expression patterns in squamous cell carcinoma and adenocarcinoma of the cervix. Mod Pathol. 2016 Jul;29(7):753-63.
Iizumi, Seiichiro et al. “MicroRNA 142-5p promotes tumor growth in oral squamous cell carcinoma via the PI3K/AKT pathway by regulating PTEN.” Heliyon vol. 7,10 e08086. 30 Sep. 2021
Gou C, Han P, Li J, Gao L, Ji X, Dong F, Su Q, Zhang Y, Liu X. Knockdown of lncRNA BLACAT1 enhances radiosensitivity of head and neck squamous cell carcinoma cells by regulating PSEN1. Br J Radiol. 2020 Apr;93(1108):20190154.
Wang L, Qu P, Yin W, Sun J. Lnc-NEAT1 induces cell apoptosis and inflammation but inhibits proliferation in a cellular model of hepatic ischemia/reperfusion injury. J Int Med Res. 2021 Mar;49(3):300060519887251.
Fang J, Qiao F, Tu J, Xu J, Ding F, Liu Y, Akuo BA, Hu J, Shao S. High expression of long non-coding RNA NEAT1 indicates poor prognosis of human cancer. Oncotarget. 2017 Jul 11;8(28):45918-45927.
Li, Xinquan et al. “Arsenic trioxide induces apoptosis in pancreatic cancer cells via changes in cell cycle, caspase activation, and GADD expression.” Pancreas vol. 27,2 (2003): 174-9.
Boulares, A H et al. “Role of poly(ADP-ribose) polymerase (PARP) cleavage in apoptosis. Caspase 3-resistant PARP mutant increases rates of apoptosis in transfected cells.” The Journal of biological chemistry vol. 274,33 (1999): 22932-40.
Rodríguez-Hernández, A et al. “Nuclear caspase-3 and caspase-7 activation, and poly(ADP-ribose) polymerase cleavage are early events in camptothecin-induced apoptosis.” Apoptosis : an international journal on programmed cell death vol. 11,1 (2006): 131-9.
Liu PF, Hu YC, Kang BH, Tseng YK, Wu PC, Liang CC, Hou YY, Fu TY, Liou HH, Hsieh IC, Ger LP, Shu CW. Expression levels of cleaved caspase-3 and caspase-3 in tumorigenesis and prognosis of oral tongue squamous cell carcinoma. PLoS One. 2017 Jul 10;12(7):e0180620.
Bredell MG, Ernst J, El-Kochairi I, Dahlem Y, Ikenberg K, Schumann DM. Current relevance of hypoxia in head and neck cancer. Oncotarget. 2016 Aug 2;7(31):50781-50804.
Shoaib M, Haseeb HM, Bano K, Arshad A. Unraveling the Complexity of Immune Checkpoint Modulation in Gastrointestinal Malignancies, Pak-Euro Journal of Medical and Life Sciences: Vol. 6, 3 (2023) Sep: 269-276.
Arshad A, Deutsch E, Vozenin MC. Simultaneous irradiation of fibroblasts and carcinoma cells repress the secretion of soluble factors able to stimulate carcinoma cell migration. PLoS One. 2015 Jan 30;10(1):e0115447.
Shafiq A, Moore J, Suleman A, Faiz S, Farooq O, Arshad A, Tehseen M, Zafar A, Ali SH, Din NU, Loya A. Elevated soluble galectin-3 as a marker of chemotherapy efficacy in breast cancer patients: A prospective study. International journal of breast cancer. 2020 Mar 14;2020.