Potential of IP-10, EGFR, CK17 and ANXA1 as Non-Invasive Biomarkers for the Diagnosis of Oral Squamous Cell Carcinoma
-
Abdolreza Mohamadnia
,
Mahta Malek
,
Hossein Dargahi
,
Mehdi Kazem Pour Dizaji
,
Mahsa Sadat Seid Saleh
,
Seyed Shahab Banihashem
,
Mohammad Bayat
,
Farnoosh Mohammadi
,
Naghmeh Bahrami
Abstract
Introduction: Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity. Early diagnosis and the identification of non-invasive biomarkers for disease monitoring are essential. This study aimed to evaluate the expression of genes involved in inflammation (IP-10), cellular proliferation (EGFR), epithelial differentiation (CK17), and cellular regulation (ANXA1) in the peripheral blood of OSCC patients compared with healthy individuals. Materials and Methods: In this case–control study, peripheral blood samples were collected from 30 OSCC patients and 30 healthy controls. Total RNA was extracted and reverse-transcribed into cDNA. Relative expression levels of IP-10 (CXCL10), EGFR, CK17, and ANXA1 were quantified using real-time polymerase chain reaction (Real-Time PCR). Statistical analyses were performed using SPSS software. Results: The expression levels of EGFR and CK17 were significantly increased in OSCC patients compared with controls (p < 0.001). Similarly, IP-10 expression was significantly upregulated in the patient group (p < 0.001). In contrast, ANXA1expression was significantly downregulated in OSCC patients (p < 0.001). Conclusion: The altered expression patterns of IP-10, EGFR, CK17, and ANXA1 in the peripheral blood of OSCC patients indicate the potential of these markers as non-invasive molecular diagnostic biomarkers. The concurrent upregulation of EGFR and CK17 may play a critical role in tumor progression, while the downregulation of ANXA1 may reflect impaired anti-inflammatory and apoptotic processes. These findings support the future application of PCR-based blood tests for OSCC screening or monitoring; however, further confirmatory studies are recommended. Keywords: Oral squamous cell carcinoma; Peripheral blood; Gene expression; EGFR; CK17; IP-10; ANXA1; Real-time PCR.
1. 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: a cancer journal for clinicians. 2021;71(3):209-49.
2. Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nature reviews Disease primers. 2020;6(1):92.
3. Rivera C. Essentials of oral cancer. International journal of clinical and experimental pathology. 2015;8(9):11884.
4. Jethwa AR, Khariwala SS. Tobacco-related carcinogenesis in head and neck cancer. Cancer and Metastasis Reviews. 2017;36(3):411-23.
5. Genet NR. Neukomm et al. 10.1073/pnas. 1406230111. Nat Rev Genet.3(3):176-88.
6. Kuttan N, Bhakthan N. Epidermal growth factor receptor (EGFR) in oral squamous cell carcinomas: overexpression, localization and therapeutic implications. Indian Journal of Dental Research: Official Publication of Indian Society for Dental Research. 1997;8(1):9-18.
7. Lemjabbar-Alaoui H, Hassan OU, Yang Y-W, Buchanan P. Lung cancer: Biology and treatment options. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2015;1856(2):189-210.
8. Escobar-Hoyos LF, Shah R, Roa-Pena L, Vanner EA, Najafian N, Banach A, et al. Keratin-17 promotes p27KIP1 nuclear export and degradation and offers potential prognostic utility. Cancer research. 2015;75(17):3650-62.
9. Sriuranpong V, Mutirangura A, Gillespie JW, Patel V, Amornphimoltham P, Molinolo AA, et al. Global gene expression profile of nasopharyngeal carcinoma by laser capture microdissection and complementary DNA microarrays. Clinical cancer research. 2004;10(15):4944-58.
10. Liu M, Guo S, Hibbert JM, Jain V, Singh N, Wilson NO, et al. CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implications. Cytokine & growth factor reviews. 2011;22(3):121-30.
11. Biaoxue R, Xiling J, Shuanying Y, Wei Z, Xiguang C, Jinsui W, et al. Upregulation of Hsp90-beta and annexin A1 correlates with poor survival and lymphatic metastasis in lung cancer patients. Journal of Experimental & Clinical Cancer Research. 2012;31(1):70.
12. DePianto D, Kerns ML, Dlugosz AA, Coulombe PA. Keratin 17 promotes epithelial proliferation and tumor growth by polarizing the immune response in skin. Nature genetics. 2010;42(10):910-4.
13. Alamdari MK, Mohamadnia A, Bayat M, Farhangiyan M, Bahrami N. Comparing the Expression Levels of GCG and FBN-1 in the Plasma of Patients with Basal Cell Carcinoma (BCC) and Healthy Individuals. Journal of Craniomaxillofacial Research. 2025:86-92.
14. Babaei P, Abbasi AJ, Mohamadnia A, Malek M, Farhangiyan M, Bahrami N. Evaluation of NCBP2 Gene Expression in Patients with Oral Squamous Cell Carcinoma Compared to Healthy Individuals. Journal of Craniomaxillofacial Research. 2025:100-5.
15. Shahriyari S, Fotook Kiaei SZ, Mohamadnia A, Farhangiyan M, Bahrami N. Investigating the Level of MUC5B Expression in the Plasma of Patients with Idiopathic Pulmonary Fibrosis (IPF) Compared to Healthy Individuals. Journal of Craniomaxillofacial Research. 2025;12(3).
16. Ghadimi K, Bahrami N, Fathi M, Farzanegan B, Naji T, Emami M, et al. Diagnostic value of LunX mRNA and CEA mRNA expression in pleural fluid of patients with non-small cell lung cancer. Minerva Pneumologica. 2017;56(2):90-5.
17. Karimi S, Bahrami N, Sharifi K, Daustany M, Baghbani-Arani F, Kazempour M, et al. Investigating gene expression level of MUC1 and CEA in pleural fluid of NSCLC lung cancer patients with real-time RT-PCR method. Minerva Pneumol. 2017;56(1):18-24.
18. Wu D, Liu X, Mu J, Yang J, Wu F, Zhou H. Therapeutic approaches targeting proteins in tumor-associated macrophages and their applications in cancers. Biomolecules. 2022;12(3):392.
19. Sugimoto MA, Vago JP, Teixeira MM, Sousa LP. Annexin A1 and the resolution of inflammation: modulation of neutrophil recruitment, apoptosis, and clearance. Journal of immunology research. 2016;2016(1):8239258.
2. Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nature reviews Disease primers. 2020;6(1):92.
3. Rivera C. Essentials of oral cancer. International journal of clinical and experimental pathology. 2015;8(9):11884.
4. Jethwa AR, Khariwala SS. Tobacco-related carcinogenesis in head and neck cancer. Cancer and Metastasis Reviews. 2017;36(3):411-23.
5. Genet NR. Neukomm et al. 10.1073/pnas. 1406230111. Nat Rev Genet.3(3):176-88.
6. Kuttan N, Bhakthan N. Epidermal growth factor receptor (EGFR) in oral squamous cell carcinomas: overexpression, localization and therapeutic implications. Indian Journal of Dental Research: Official Publication of Indian Society for Dental Research. 1997;8(1):9-18.
7. Lemjabbar-Alaoui H, Hassan OU, Yang Y-W, Buchanan P. Lung cancer: Biology and treatment options. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2015;1856(2):189-210.
8. Escobar-Hoyos LF, Shah R, Roa-Pena L, Vanner EA, Najafian N, Banach A, et al. Keratin-17 promotes p27KIP1 nuclear export and degradation and offers potential prognostic utility. Cancer research. 2015;75(17):3650-62.
9. Sriuranpong V, Mutirangura A, Gillespie JW, Patel V, Amornphimoltham P, Molinolo AA, et al. Global gene expression profile of nasopharyngeal carcinoma by laser capture microdissection and complementary DNA microarrays. Clinical cancer research. 2004;10(15):4944-58.
10. Liu M, Guo S, Hibbert JM, Jain V, Singh N, Wilson NO, et al. CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implications. Cytokine & growth factor reviews. 2011;22(3):121-30.
11. Biaoxue R, Xiling J, Shuanying Y, Wei Z, Xiguang C, Jinsui W, et al. Upregulation of Hsp90-beta and annexin A1 correlates with poor survival and lymphatic metastasis in lung cancer patients. Journal of Experimental & Clinical Cancer Research. 2012;31(1):70.
12. DePianto D, Kerns ML, Dlugosz AA, Coulombe PA. Keratin 17 promotes epithelial proliferation and tumor growth by polarizing the immune response in skin. Nature genetics. 2010;42(10):910-4.
13. Alamdari MK, Mohamadnia A, Bayat M, Farhangiyan M, Bahrami N. Comparing the Expression Levels of GCG and FBN-1 in the Plasma of Patients with Basal Cell Carcinoma (BCC) and Healthy Individuals. Journal of Craniomaxillofacial Research. 2025:86-92.
14. Babaei P, Abbasi AJ, Mohamadnia A, Malek M, Farhangiyan M, Bahrami N. Evaluation of NCBP2 Gene Expression in Patients with Oral Squamous Cell Carcinoma Compared to Healthy Individuals. Journal of Craniomaxillofacial Research. 2025:100-5.
15. Shahriyari S, Fotook Kiaei SZ, Mohamadnia A, Farhangiyan M, Bahrami N. Investigating the Level of MUC5B Expression in the Plasma of Patients with Idiopathic Pulmonary Fibrosis (IPF) Compared to Healthy Individuals. Journal of Craniomaxillofacial Research. 2025;12(3).
16. Ghadimi K, Bahrami N, Fathi M, Farzanegan B, Naji T, Emami M, et al. Diagnostic value of LunX mRNA and CEA mRNA expression in pleural fluid of patients with non-small cell lung cancer. Minerva Pneumologica. 2017;56(2):90-5.
17. Karimi S, Bahrami N, Sharifi K, Daustany M, Baghbani-Arani F, Kazempour M, et al. Investigating gene expression level of MUC1 and CEA in pleural fluid of NSCLC lung cancer patients with real-time RT-PCR method. Minerva Pneumol. 2017;56(1):18-24.
18. Wu D, Liu X, Mu J, Yang J, Wu F, Zhou H. Therapeutic approaches targeting proteins in tumor-associated macrophages and their applications in cancers. Biomolecules. 2022;12(3):392.
19. Sugimoto MA, Vago JP, Teixeira MM, Sousa LP. Annexin A1 and the resolution of inflammation: modulation of neutrophil recruitment, apoptosis, and clearance. Journal of immunology research. 2016;2016(1):8239258.
| Files | ||
| Issue | Vol 13, No 1 (Winter 2026) | |
| Section | Original Article(s) | |
| Keywords | ||
| Oral squamous cell carcinoma; Peripheral blood; Gene expression; EGFR; CK17; IP-10; ANXA1; Real-time PCR. | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Mohamadnia A, Malek M, Dargahi H, Kazem Pour Dizaji M, Seid Saleh MS, Banihashem SS, Bayat M, Mohammadi F, Bahrami N. Potential of IP-10, EGFR, CK17 and ANXA1 as Non-Invasive Biomarkers for the Diagnosis of Oral Squamous Cell Carcinoma. J Craniomaxillofac Res. 2026;13(1):105-112.
