Transcriptomic Analysis of HPV-Positive Oesophageal Tissue Reveals Upregulation of Genes Linked to Cell Cycle and DNA Replication
<p>Differentially expressed genes between HPV-positive and HPV-negative non-cancerous human oesophageal tissue samples <span class="html-italic">p</span>-value (<span class="html-italic">p</span> < 0.001).</p> "> Figure 2
<p>Complete upstream pathways connecting enriched transcription factors to kinases through known protein-protein interaction. Red nodes highlight top transcription factors predicted to regulate our upregulated genes. Grey nodes depict proteins that interact with these transcription factors. Blue nodes represent kinases predicted to phosphorylate within the network. Green lines represent phosphorylation interactions between kinases and their targets, while grey lines indicate protein-protein physical interactions. Adapted with permission from Ref [<a href="#B9-ijms-26-00056" class="html-bibr">9</a>]. Copyright 2012, Ma’ayan Lab.</p> ">
Abstract
:1. Introduction
2. Results
2.1. Pathological Characteristics and Detection of HR-HPV
2.2. Transcriptomic Profiling of Non-Cancerous Oesophageal Tissue with and Without HR-HPV Infection
2.3. Analysis of Differentially Expressed Genes of Non-Cancerous Oesophageal Tissue with and Without HR-HPV Infection Using Pathway Enrichment Analysis
2.4. Investigation of Differentially Expressed Genes of Non-Cancerous Oesophageal Tissue with and Without HR-HPV Infection via Kinase Enrichment Analysis
3. Discussion
4. Materials and Methods
4.1. Oesophageal Tissue Specimen Collection
4.2. Genomic Material Extraction and Purification
4.3. Detection and Genotyping of HPV DNA
4.4. RNA Sequencing
4.5. Bioinformatics Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Graham, S.V. The Human Papillomavirus Replication Cycle, and Its Links to Cancer Progression: A Comprehensive Review. Clin. Sci. 2017, 131, 2201–2221. [Google Scholar] [CrossRef]
- Kombe Kombe, A.J.; Li, B.; Zahid, A.; Mengist, H.M.; Bounda, G.-A.; Zhou, Y.; Jin, T. Epidemiology and Burden of Human Papillomavirus and Related Diseases, Molecular Pathogenesis, and Vaccine Evaluation. Front. Public Health 2021, 8, 552028. [Google Scholar] [CrossRef]
- de Sanjosé, S.; Brotons, M.; Pavón, M.A. The Natural History of Human Papillomavirus Infection. Best Pract. Res. Clin. Obstet. Gynaecol. 2018, 47, 2–13. [Google Scholar] [CrossRef]
- Tramontano, L.; Sciorio, R.; Bellaminutti, S.; Esteves, S.C.; Petignat, P. Exploring the Potential Impact of Human Papillomavirus on Infertility and Assisted Reproductive Technology Outcomes. Reprod. Biol. 2023, 23, 100753. [Google Scholar] [CrossRef] [PubMed]
- Ashrafi, G.H.; Haghshenas, M.R.; Marchetti, B.; O’Brien, P.M.; Campo, M.S. E5 Protein of Human Papillomavirus Type 16 Selectively Downregulates Surface HLA Class I. Int. J. Cancer 2005, 113, 276–283. [Google Scholar] [CrossRef]
- Ashrafi, G.H.; Salman, N.A. Pathogenesis of Human Papillomavirus—Immunological Responses to HPV Infection. In Human Papillomavirus—Research in a Global Perspective; InTech: Vienna, Austria, 2016; Available online: https://books.google.co.uk/books?hl=en&lr=&id=6XuQDwAAQBAJ&oi=fnd&pg=PA243&dq=6.%09Ashrafi,+G.H.%3B+Salman,+N.A.+Pathogenesis+of+Human+Papillomavirus%E2%80%94Immunological+Responses+to+HPV+Infection.+In+Human+Papillomavirus%E2%80%94Research+in+a+Global+Perspective%3B+InTech:+Vienna,+Austria,+++2016&ots=6wv91F5jus&sig=I2nfaiqYruKkQKlXXOPRWAwl8cs#v=onepage&q&f=false (accessed on 16 October 2024).
- Bhattacharjee, R.; Das, S.S.; Biswal, S.S.; Nath, A.; Das, D.; Basu, A.; Malik, S.; Kumar, L.; Kar, S.; Singh, S.K.; et al. Mechanistic Role of HPV-Associated Early Proteins in Cervical Cancer: Molecular Pathways and Targeted Therapeutic Strategies. Crit. Rev. Oncol. Hematol. 2022, 174, 103675. [Google Scholar] [CrossRef]
- National Center for Biotechnology Information (NCBI) [Internet]. National Library of Medicine (US), National Center for Biotechnology Information: Bethesda, MD, USA, 1988. Available online: https://www.ncbi.nlm.nih.gov/ (accessed on 12 December 2024).
- Chen, E.Y.; Xu, H.; Gordonov, S.; Lim, M.P.; Perkins, M.H.; Ma’ayan, A. Expression2Kinases: MRNA Profiling Linked to Multiple Upstream Regulatory Layers. Bioinformatics 2012, 28, 105–111. [Google Scholar] [CrossRef]
- Jensen, J.E.; Becker, G.L.; Jackson, J.B.; Rysavy, M.B. Human Papillomavirus and Associated Cancers: A Review. Viruses 2024, 16, 680. [Google Scholar] [CrossRef] [PubMed]
- Pešut, E.; Đukić, A.; Lulić, L.; Skelin, J.; Šimić, I.; Milutin Gašperov, N.; Tomaić, V.; Sabol, I.; Grce, M. Human Papillomaviruses-Associated Cancers: An Update of Current Knowledge. Viruses 2021, 13, 2234. [Google Scholar] [CrossRef]
- Syrjänen, K.; Pyrhönen, S.; Aukee, S.; Koskela, E. Squamous Cell Papilloma of the Esophagus: A Tumour Probably Caused by Human Papilloma Virus (HPV). Diagn. Histopathol. 1982, 5, 291–296. [Google Scholar] [PubMed]
- Abbas, G.; Krasna, M. Overview of Esophageal Cancer. Ann. Cardiothorac. Surg. 2017, 6, 131–136. [Google Scholar] [CrossRef] [PubMed]
- Jing, Y.; Wang, T.; Chen, Z.; Ding, X.; Xu, J.; Mu, X.; Cao, M.; Chen, H. Phylogeny and Polymorphism in the Long Control Regions E6, E7, and L1 of HPV Type 56 in Women from Southwest China. Mol. Med. Rep. 2018, 17, 7131–7141. [Google Scholar] [CrossRef] [PubMed]
- Mesher, D.; Soldan, K.; Lehtinen, M.; Beddows, S.; Brisson, M.; Brotherton, J.M.L.; Chow, E.P.F.; Cummings, T.; Drolet, M.; Fairley, C.K.; et al. Population-Level Effects of Human Papillomavirus Vaccination Programs on Infections with Nonvaccine Genotypes. Emerg. Infect. Dis. 2016, 22, 1732–1740. [Google Scholar] [CrossRef]
- Letafati, A.; Motlaghzadeh, S.; Ardekani, O.S.; Memarpour, B.; Seyedi, S.; Bahari, M.; Farahani, A.V.; Khoshravan, A.; Sarrafzadeh, S.; Vasmehjani, A.A.; et al. Uncommon High Distribution of HPV-16, HPV-54, and HPV-56 in Female Referred to a Laboratory in Karaj, Iran: Indications of a Paradigm Shift in HPV Genotypes? Virol. J. 2024, 21, 182. [Google Scholar] [CrossRef] [PubMed]
- Hanahan, D.; Weinberg, R.A. The Hallmarks of Cancer. Cell 2000, 100, 57–70. [Google Scholar] [CrossRef] [PubMed]
- Lu, Y.; Su, F.; Yang, H.; Xiao, Y.; Zhang, X.; Su, H.; Zhang, T.; Bai, Y.; Ling, X. E2F1 Transcriptionally Regulates CCNA2 Expression to Promote Triple Negative Breast Cancer Tumorigenicity. Cancer Biomark. 2022, 33, 57–70. [Google Scholar] [CrossRef]
- Manning, J.; Kumar, S. NEDD1: Function in Microtubule Nucleation, Spindle Assembly and Beyond. Int. J. Biochem. Cell Biol. 2007, 39, 7–11. [Google Scholar] [CrossRef] [PubMed]
- Peng, Q.; Wen, T.; Liu, D.; Wang, S.; Jiang, X.; Zhao, S.; Huang, G. DSN1 Is a Prognostic Biomarker and Correlated with Clinical Characterize in Breast Cancer. Int. Immunopharmacol. 2021, 101, 107605. [Google Scholar] [CrossRef] [PubMed]
- Chuang, T.-P.; Wang, J.-Y.; Jao, S.-W.; Wu, C.-C.; Chen, J.-H.; Hsiao, K.-H.; Lin, C.-Y.; Chen, S.-H.; Su, S.-Y.; Chen, Y.-J.; et al. Over-Expression of AURKA, SKA3 and DSN1 Contributes to Colorectal Adenoma to Carcinoma Progression. Oncotarget 2016, 7, 45803–45818. [Google Scholar] [CrossRef]
- Duensing, S.; Münger, K. Human Papillomaviruses and Centrosome Duplication Errors: Modeling the Origins of Genomic Instability. Oncogene 2002, 21, 6241–6248. [Google Scholar] [CrossRef]
- Scarth, J.A.; Patterson, M.R.; Morgan, E.L.; Macdonald, A. The Human Papillomavirus Oncoproteins: A Review of the Host Pathways Targeted on the Road to Transformation. J. Gen. Virol. 2021, 102, 001540. [Google Scholar] [CrossRef] [PubMed]
- Yeeles, J.T.P.; Deegan, T.D.; Janska, A.; Early, A.; Diffley, J.F.X. Regulated Eukaryotic DNA Replication Origin Firing with Purified Proteins. Nature 2015, 519, 431–435. [Google Scholar] [CrossRef] [PubMed]
- Cheng, J.; Lu, X.; Wang, J.; Zhang, H.; Duan, P.; Li, C. Interactome Analysis of Gene Expression Profiles of Cervical Cancer Reveals Dysregulated Mitotic Gene Clusters. Am. J. Transl. Res. 2017, 9, 3048–3059. [Google Scholar] [PubMed]
- Ghongane, P.; Kapanidou, M.; Asghar, A.; Elowe, S.; Bolanos-Garcia, V.M. The Dynamic Protein Knl1—A Kinetochore Rendezvous. J. Cell Sci. 2014, 127, 3415–3423. [Google Scholar] [CrossRef] [PubMed]
- Cui, Y.; Zhang, C.; Ma, S.; Guo, W.; Cao, W.; Guan, F. CASC5 Is a Potential Tumour Driving Gene in Lung Adenocarcinoma. Cell Biochem. Funct. 2020, 38, 733–742. [Google Scholar] [CrossRef]
- Hanahan, D.; Weinberg, R.A. Hallmarks of Cancer: The Next Generation. Cell 2011, 144, 646–674. [Google Scholar] [CrossRef] [PubMed]
- Boyer, S.N.; Wazer, D.E.; Band, V. E7 Protein of Human Papilloma Virus-16 Induces Degradation of Retinoblastoma Protein through the Ubiquitin-Proteasome Pathway. Cancer Res. 1996, 56, 4620–4624. [Google Scholar] [PubMed]
- Bieging, K.T.; Mello, S.S.; Attardi, L.D. Unravelling Mechanisms of P53-Mediated Tumour Suppression. Nat. Rev. Cancer 2014, 14, 359–370. [Google Scholar] [CrossRef]
- Cox, J.T.; Schiffman, M.; Solomon, D. Prospective Follow-up Suggests Similar Risk of Subsequent Cervical Intraepithelial Neoplasia Grade 2 or 3 among Women with Cervical Intraepithelial Neoplasia Grade 1 or Negative Colposcopy and Directed Biopsy. Am. J. Obstet. Gynecol. 2003, 188, 1406–1412. [Google Scholar] [CrossRef] [PubMed]
- Kitchener, H.C.; Almonte, M.; Wheeler, P.; Desai, M.; Gilham, C.; Bailey, A.; Sargent, A.; Peto, J. HPV Testing in Routine Cervical Screening: Cross Sectional Data from the ARTISTIC Trial. Br. J. Cancer 2006, 95, 56–61. [Google Scholar] [CrossRef]
- Derchain, S.F.; Sarian, L.O.; Naud, P.; Roteli-Martins, C.; Longatto-Filho, A.; Tatti, S.; Branca, M.; Eržen, M.; Serpa-Hammes, L.; Matos, J.; et al. Safety of Screening with Human Papillomavirus Testing for Cervical Cancer at Three-Year Intervals in a High-Risk Population: Experience from the LAMS Study. J. Med. Screen. 2008, 15, 97–104. [Google Scholar] [CrossRef] [PubMed]
- Gillison, M.L.; Broutian, T.; Pickard, R.K.L.; Tong, Z.; Xiao, W.; Kahle, L.; Graubard, B.I.; Chaturvedi, A.K. Prevalence of Oral HPV Infection in the United States, 2009–2010. JAMA 2012, 307, 693. [Google Scholar] [CrossRef] [PubMed]
- Giuliano, A.R.; Viscidi, R.; Torres, B.N.; Ingles, D.J.; Sudenga, S.L.; Villa, L.L.; Luiza Baggio, M.; Abrahamsen, M.; Quiterio, M.; Salmeron, J.; et al. Seroconversion Following Anal and Genital HPV Infection in Men: The HIM Study. Papillomavirus Res. 2015, 1, 109–115. [Google Scholar] [CrossRef] [PubMed]
- Waghray, A.; Schober, M.; Feroze, F.; Yao, F.; Virgin, J.; Chen, Y.Q. Identification of Differentially Expressed Genes by Serial Analysis of Gene Expression in Human Prostate Cancer. Cancer Res. 2001, 61, 4283–4286. [Google Scholar] [PubMed]
- Rakha, E.A.; Pinder, S.E.; Paish, E.C.; Robertson, J.F.; Ellis, I.O. Expression of E2F-4 in Invasive Breast Carcinomas Is Associated with Poor Prognosis. J. Pathol. 2004, 203, 754–761. [Google Scholar] [CrossRef] [PubMed]
- Rakha, E.A.; Armour, J.A.L.; Pinder, S.E.; Paish, C.E.; Ellis, I.O. High-resolution Analysis of 16q22.1 in Breast Carcinoma Using DNA Amplifiable Probes (Multiplex Amplifiable Probe Hybridization Technique) and Immunohistochemistry. Int. J. Cancer 2005, 114, 720–729. [Google Scholar] [CrossRef]
- Hsu, J.; Sage, J. Novel Functions for the Transcription Factor E2F4 in Development and Disease. Cell Cycle 2016, 15, 3183–3190. [Google Scholar] [CrossRef] [PubMed]
- Zheng, Q.; Fu, Q.; Xu, J.; Gu, X.; Zhou, H.; Zhi, C. Transcription Factor E2F4 Is an Indicator of Poor Prognosis and Is Related to Immune Infiltration in Hepatocellular Carcinoma. J. Cancer 2021, 12, 1792–1803. [Google Scholar] [CrossRef] [PubMed]
- Qi, L.; Ren, Z.; Li, W. E2F4 Transcription Factor Is a Prognostic Biomarker Related to Immune Infiltration of Head and Neck Squamous Cell Carcinoma. Sci. Rep. 2022, 12, 12132. [Google Scholar] [CrossRef]
- Liao, G.-B.; Li, X.-Z.; Zeng, S.; Liu, C.; Yang, S.-M.; Yang, L.; Hu, C.-J.; Bai, J.-Y. Regulation of the Master Regulator FOXM1 in Cancer. Cell Commun. Signal. 2018, 16, 57. [Google Scholar] [CrossRef] [PubMed]
- Rachmadi, L.; Billianti Susanto, Y.D.; Sitinjak, D.; Manatar, A.F.; Saraswati, M.; Adham, M. HPV Infection Is Associated with FoxM1 Overexpression in Dysplastic Changes of Sinonasal Inverted Papilloma. Asian Pac. J. Cancer Prev. 2022, 23, 4293–4298. [Google Scholar] [CrossRef] [PubMed]
- Strum, S.W.; Gyenis, L.; Litchfield, D.W. CSNK2 in Cancer: Pathophysiology and Translational Applications. Br. J. Cancer 2022, 126, 994–1003. [Google Scholar] [CrossRef] [PubMed]
- Bae, J.S.; Park, S.-H.; Jamiyandorj, U.; Kim, K.M.; Noh, S.J.; Kim, J.R.; Park, H.J.; Kwon, K.S.; Jung, S.H.; Park, H.S.; et al. CK2α/CSNK2A1 Phosphorylates SIRT6 and Is Involved in the Progression of Breast Carcinoma and Predicts Shorter Survival of Diagnosed Patients. Am. J. Pathol. 2016, 186, 3297–3315. [Google Scholar] [CrossRef] [PubMed]
- Jiang, C.; Ma, Z.; Zhang, G.; Yang, X.; Du, Q.; Wang, W. CSNK2A1 Promotes Gastric Cancer Invasion Through the PI3K-Akt-MTOR Signaling Pathway. Cancer Manag. Res. 2019, 11, 10135–10143. [Google Scholar] [CrossRef]
- Baker, S.J.; Poulikakos, P.I.; Irie, H.Y.; Parekh, S.; Reddy, E.P. CDK4: A Master Regulator of the Cell Cycle and Its Role in Cancer. Genes Cancer 2022, 13, 21–45. [Google Scholar] [CrossRef] [PubMed]
- Deshpande, A.; Sicinski, P.; Hinds, P.W. Cyclins and Cdks in Development and Cancer: A Perspective. Oncogene 2005, 24, 2909–2915. [Google Scholar] [CrossRef]
- Jungert, K.; Buck, A.; von Wichert, G.; Adler, G.; König, A.; Buchholz, M.; Gress, T.M.; Ellenrieder, V. Sp1 Is Required for Transforming Growth Factor-β–Induced Mesenchymal Transition and Migration in Pancreatic Cancer Cells. Cancer Res. 2007, 67, 1563–1570. [Google Scholar] [CrossRef] [PubMed]
- Engeland, K. Cell Cycle Regulation: P53-P21-RB Signaling. Cell Death Differ. 2022, 29, 946–960. [Google Scholar] [CrossRef] [PubMed]
- Nguyen, L.C.; Yang, D.; Nicolaescu, V.; Best, T.J.; Gula, H.; Saxena, D.; Gabbard, J.D.; Chen, S.-N.; Ohtsuki, T.; Friesen, J.B.; et al. Cannabidiol Inhibits SARS-CoV-2 Replication through Induction of the Host ER Stress and Innate Immune Responses. Sci. Adv. 2022, 8, eabi6110. [Google Scholar] [CrossRef] [PubMed]
- Chen, B.J.; Huang, S.; Janitz, M. Changes in Circular RNA Expression Patterns during Human Foetal Brain Development. Genomics 2019, 111, 753–758. [Google Scholar] [CrossRef] [PubMed]
- World Health Organization (WHO). Guidance on Regulations for the Transport of Infectious Substances, 2023–2024; World Health Organization: Geneva, Switzerland, 2024. [Google Scholar]
- Jiang, H.; Lei, R.; Ding, S.-W.; Zhu, S. Skewer: A Fast and Accurate Adapter Trimmer for next-Generation Sequencing Paired-End Reads. BMC Bioinform. 2014, 15, 182. [Google Scholar] [CrossRef] [PubMed]
- Dobin, A.; Davis, C.A.; Schlesinger, F.; Drenkow, J.; Zaleski, C.; Jha, S.; Batut, P.; Chaisson, M.; Gingeras, T.R. STAR: Ultrafast Universal RNA-Seq Aligner. Bioinformatics 2013, 29, 15–21. [Google Scholar] [CrossRef]
- Love, M.I.; Huber, W.; Anders, S. Moderated Estimation of Fold Change and Dispersion for RNA-Seq Data with DESeq2. Genome Biol. 2014, 15, 550. [Google Scholar] [CrossRef]
- Subramanian, A.; Tamayo, P.; Mootha, V.K.; Mukherjee, S.; Ebert, B.L.; Gillette, M.A.; Paulovich, A.; Pomeroy, S.L.; Golub, T.R.; Lander, E.S.; et al. Gene Set Enrichment Analysis: A Knowledge-Based Approach for Interpreting Genome-Wide Expression Profiles. Proc. Natl. Acad. Sci. USA 2005, 102, 15545–15550. [Google Scholar] [CrossRef] [PubMed]
- Liberzon, A.; Birger, C.; Thorvaldsdóttir, H.; Ghandi, M.; Mesirov, J.P.; Tamayo, P. The Molecular Signatures Database Hallmark Gene Set Collection. Cell Syst. 2015, 1, 417–425. [Google Scholar] [CrossRef] [PubMed]
- Xie, Z.; Bailey, A.; Kuleshov, M.V.; Clarke, D.J.B.; Evangelista, J.E.; Jenkins, S.L.; Lachmann, A.; Wojciechowicz, M.L.; Kropiwnicki, E.; Jagodnik, K.M.; et al. Gene Set Knowledge Discovery with Enrichr. Curr. Protoc. 2021, 1, e90. [Google Scholar] [CrossRef] [PubMed]
- Chen, E.Y.; Tan, C.M.; Kou, Y.; Duan, Q.; Wang, Z.; Meirelles, G.V.; Clark, N.R.; Ma’ayan, A. Enrichr: Interactive and Collaborative HTML5 Gene List Enrichment Analysis Tool. BMC Bioinform. 2013, 14, 128. [Google Scholar] [CrossRef]
- Kuleshov, M.V.; Jones, M.R.; Rouillard, A.D.; Fernandez, N.F.; Duan, Q.; Wang, Z.; Koplev, S.; Jenkins, S.L.; Jagodnik, K.M.; Lachmann, A.; et al. Enrichr: A Comprehensive Gene Set Enrichment Analysis Web Server 2016 Update. Nucleic Acids Res. 2016, 44, W90–W97. [Google Scholar] [CrossRef] [PubMed]
- Clarke, D.J.B.; Kuleshov, M.V.; Schilder, B.M.; Torre, D.; Duffy, M.E.; Keenan, A.B.; Lachmann, A.; Feldmann, A.S.; Gundersen, G.W.; Silverstein, M.C.; et al. EXpression2Kinases (X2K) Web: Linking Expression Signatures to Upstream Cell Signaling Networks. Nucleic Acids Res. 2018, 46, W171–W179. [Google Scholar] [CrossRef]
Description | Number of Overlapping Genes | p-Value | Overlapping Genes |
---|---|---|---|
Cell Cycle | 7 | 7.49 × 10−8 | TOP2A; CCNA2; NEDD1; DSN1; NUP107; CASC5; MCM10 |
DNA Replication | 5 | 8.69 × 10−5 | CCNA2; DSN1; NUP107; CASC5; MCM10 |
(A) | |
Transcription Factors | p-Value |
E2F4 | 1.6 × 10−8 |
FOXM1 | 1.5 × 10−4 |
CEBPD | 9.1 × 10−4 |
(B) | |
Regulatory Kinases | p-Value |
CSNK2A1 | 2.2 × 10−15 |
CDK4 | 7.0 × 10−15 |
MAPK14 | 1.05 × 10−12 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Shafiq, M.O.; Cakir, M.O.; Bilge, U.; Pasha, Y.; Ashrafi, G.H. Transcriptomic Analysis of HPV-Positive Oesophageal Tissue Reveals Upregulation of Genes Linked to Cell Cycle and DNA Replication. Int. J. Mol. Sci. 2025, 26, 56. https://doi.org/10.3390/ijms26010056
Shafiq MO, Cakir MO, Bilge U, Pasha Y, Ashrafi GH. Transcriptomic Analysis of HPV-Positive Oesophageal Tissue Reveals Upregulation of Genes Linked to Cell Cycle and DNA Replication. International Journal of Molecular Sciences. 2025; 26(1):56. https://doi.org/10.3390/ijms26010056
Chicago/Turabian StyleShafiq, Muhammad Osama, Muharrem Okan Cakir, Ugur Bilge, Yasmin Pasha, and G. Hossein Ashrafi. 2025. "Transcriptomic Analysis of HPV-Positive Oesophageal Tissue Reveals Upregulation of Genes Linked to Cell Cycle and DNA Replication" International Journal of Molecular Sciences 26, no. 1: 56. https://doi.org/10.3390/ijms26010056
APA StyleShafiq, M. O., Cakir, M. O., Bilge, U., Pasha, Y., & Ashrafi, G. H. (2025). Transcriptomic Analysis of HPV-Positive Oesophageal Tissue Reveals Upregulation of Genes Linked to Cell Cycle and DNA Replication. International Journal of Molecular Sciences, 26(1), 56. https://doi.org/10.3390/ijms26010056