HISTOLOGICAL AND MOLECULAR STUDY OF HOXB4 GENE IN CERVICAL CANCER AND BENIGN
Abstract
Cervical cancer (CC) is one of the most common malignant tumors in women, with 604,000 new cases and 342,000 deaths in 2021 (1). Carcinoma of the cervix is the fourth most common health problem worldwide among women (2). Carcinoma cervix is caused by human papilloma virus (HPV), which is the most common sexually transmitted infection, has been shown to be related to UCC. This study was carried out in Laboratories of the College of Science/ Department of Biology and in a local lab during the period between December 2021 to August 2022. The study of PCR was used to detection HOXB4 expression. We aimed to describe the histological changes of tumors malignant and benign and normal tissues of the cervical and determine the relationships between HOXB4 expression with the histopathological variables involving, stage, grade, muscle and lymph nodes invasiveness and histological types. results shows the values of HOXB4 expression and a significant difference (P-value>0.001) between patients with cervical cancer and control group, these results regarding the values means of HOXB4expression a significant difference (P-value=0.021) between patients with benign tumor and the control and the values means of HOXB4 expression a significantly difference (P-value >0.001) between patients with cervical cancer and benign tumor.
References
2. Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R. L.; Torre, L. A. and Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries CA Cancer J. Clin, 68 (6): 394-424.
3. Garbuglia, A. R.; Lapa, D.; Sias, C.; Capobianchi, M. R. and Del Porto, P. (2020). The Use of Both Therapeutic and Prophy Prophylactic Vaccines in the Therapy of Papilloma virus Disease. Front Immunol J. 11: 188.
4. Manganaro, L.; Lakhman, Y.; Bharwani, N.; Gui, B.; Gigli, S.; Vinci, V.; Rizzo, S.; Kido, A.; Cunha, T. M.; Sala, E.; Rockall, A.; Forstner, R. and Nougaret, S. (2021). Staging, recurrence and follow-up of uterine cervical cancer using MRI: Updated Guidelines of the European Society of Urogenital Radiology after revised FIGO staging 2018. Eur. Radiol J. 31(1): 7802–7816.
5. Balcacer, P.; Shergill, A. and Litkouhi, B. (2019). MRI of cervical cancer with a surgical perspective: Staging, prognostic implications and pitfalls. Abdom. Radiol. 44(1): 2557–2571.
6. Babion, I ; Jaspers, A.; van Splunter, A. P.; van der Hoorn, I. A. E.; Wilting, S. M. and Steenbergen, R. D. M. (. (2020 miR-9-5p Exerts a Dual Role in Cervical Cancer and Targets Transcription Factor TWIST1. Journal of Cells. 65 : (1)9
7. Pramana, C.; Lia Sasdes Mangiri, L. S.; Yesisca, Y. and Chendra, L. (2023). Treatment of Cervical Leiomyoma: Case Report and Literature Review. J Complement Med Res. 14(1): 37-41.
8. Esmat, E ; Malakzai, H. A.; Haidari, M.; Haidary, A. M.; Baha, M. and Abdul-Ghafar, J. (2021). Giant hamartomatous polyp of the uterine cervix with heterologous mesenchymal tissue in a child: a case report. J Med Case Rep. 15(1): 279.
9. Entrez Gene: HOXB4 homeobox B4.
10. Lei, D.; Yang, W. & Zheng, P. (2021). HOXB4 inhibits the proliferation and tumorigenesis of cervical cancer cells by downregulating the activity of Wnt/β-catenin signaling pathway. Cell Death & Disease Journal. 12: 105.
11. Agarwa, N.; Gupta, M. and Agrawal, A. . (2023). Colposcopic Evaluation Using Swede Score as a Tool to Screen Suspicious-looking Cervix and its Correlation to Histopathological Findings. J South Asian Feder Obst Gynae. 15(2): 188–192.
12. Herlana, F., Nur, I. M., & Purbaningsih, W. (2017). Karakteristik Pasien Kanker Serviks berdasar atas Usia, Paritas, dan Gambaran Histopatologi di RSUD Al-Ihsan Bandung. In Bandung Meeting on Global Medicine & Health (BaMGMH). 1(1): 138-142.
13. Zhu, J.; Cao, L.; Wen, H.; Bi, R.; Wu, X. and Ke. G. (2020). The clinical and prognostic implication of deep stromal invasion in cervical cancer patients undergoing radical hysterectomy. J Cancer. 11(24): 7368–7377.
14. Eni, A. O.; Ndukwe, C. O.; Olusina, D. B.; Nnakenyi, N. F.; Nzegwu, M. A.; Eluke, C. C.; Ukekwe, F. I.; Chiemeka, M. E., Aniume, I. O.; Nwokoro, O. C. (2023). Spectrum, Clinicopathologic Profile, and p16 Expression Pattern of Nonmalignant Cervical Tissues in Enugu, South-East Nigeria. Ibnosina J Med Biomed Sci 15(3): 121–128.
15. Kaur, S.; Piplani, S.; Madan, M. and Gill, K. S. (2023). Expression of p16 in Cervical Intraepithelial Neoplasm and Invasive Cervical Carcinoma: An immunohistochemical study. International Journal of Clinical and Diagnostic Pathology. 6(1): 01-04.
16. Blaggan, A.; Bal, M. S.; Sharma, A.; Gupta, N. and Gupta, M. (2023). Study of pap smears for cervical cancer screening and its correlation with cervical biopsy in Himachali women. International Journal of Life Sciences, Biotechnologyand PharmaResearch. 12 (2): 2250-3137.
17. Vinzuda, A.; Patel, P. R.; Tailor, H. J. and Tilala, A. (2023). Histopathological study of hysterectomy specimens- astudy at tertiary cancer hospital. Int J Acad Med Pharm. 5(4): 920-924.
18. Winata, I. G. S.; Setiawan, W. A. and Nyoman Gede Dikawijaya Satriawa, N. G. D. (2023). Neoadjuvant chemotherapy respones of cervical cancer patient stage IIB in sanglah general hospital denpasar. International Journal of Innovation Scientific Research and Review. 5(5): 4479-4482.
19. Herlana, F., Nur, I. M., & Purbaningsih, W. (2017). Karakteristik Pasien Kanker Serviks berdasar atas Usia, Paritas, dan Gambaran Histopatologi di RSUD Al-Ihsan Bandung. In Bandung Meeting on Global Medicine & Health (BaMGMH). 1(1): 138-142.
20. Nanthamongkolkul, K. and Hanprasertpong, J. (2018). Predictive Factors of Pelvic Lymph Node Metastasis in Early-Stage Cervical Cancer. Oncol Res Treat J. 41 (4): 194–198.
21. Winata, I. G. S.; Setiawan, W. A. and Nyoman Gede Dikawijaya Satriawa, N. G. D. (2023). Neoadjuvant chemotherapy respones of cervical cancer patient stage IIB in sanglah general hospital denpasar. International Journal of Innovation Scientific Research and Review. 5(5): 4479-4482.
22. Ghardon, S. S. L.; Hemida ; R.; Borg, M. A. Sallam, H. F. and Ahmed, H. M. (2022). Correlative study between apparent difusion coefcient value and grading of cervical cancer. Egypt J Radiol Nucl Med. 53(1): 170.
23. Cooley, J. J. P.; Maguire, F. B.; Morris, C. R; Parikh-Patel, A; Abrahão, R.; Chen, H. A. and Keegan, T. H. M. (2023). Cervical Cancer Stage at Diagnosis and Survival among Women ≥65 Years in California. Cancer Epidemiol Biomarkers Prev Journal. 32 (1): 91–97.
24. Xu, Z.; Yang, L.; Yu, H. and Guo, L. (2022). A machine learning model for grade 4 lymphopenia prediction during pelvic radiotherapy in patients with cervical cancer. Front Oncol Journal. 12(1): 905222.
25. Xu, M.; Xie, X.; Cai, L.; Xie, Y.; Gao, Q. and Sun, P. (2022). Risk Factor Assessment of Lymph Node Metastasis in Patients With FIGO Stage IB1 Cervical Cancer. Front Oncol J. 12 (1): 809159.
26. Jeong, S. Y.; Park, B. K.; Chel Hun Choi, C. H.; Lee, Y-Y.; Kim, T-J.; Lee, J-W and Kim, B-G. (2021). Utility of 3T MRI in Women with IB1 Cervical Cancer in Determining the Necessity of Less Invasive Surgery. Cancers Journal. 14(1): 224.
27. Meng, Y.; Yan, X. and Fan, J. (2023). Construction of prediction model of lymph node metastasis of early cervical cancer based on machine learning algorithm and its application: experience of 204 cases in a single center. Am J Transl Res. 2023; 15(3): 1852–1861.
28. Guani, B.; Gaillard, T.; Teo-Fortin, L.; Balaya, V.; Feki, A.; Paoletti, X.; Mathevet, P.; Plante, M. and Lecuru, F. (2022). Estimation risk of lymph nodal invasion in patients with early-stage cervical cancer: Cervical cancer application. Front Oncol J. 12(1): 935628.
29. Shanmukhi, V. B. and M. Vijaya Sree, M. V. (2023). Revisiting indication for hysterectomy according to PALM-COEIN classification and its correlation with histopathological examination reports. Int J Reprod Contracept Obstet Gynecol. 12(7): 2145-2150.
30. Vinzuda, A.; Patel, P. R.; Tailor, H. J. and Tilala, A. (2023). Histopathological study of hysterectomy specimens- astudy at tertiary cancer hospital. Int J Acad Med Pharm. 5(4): 920-924.
31. Ferrari, F.; Forte, S.; Valenti, G.; Ardighieri, L.; Barra, F.; Esposito, V.; Sartori, E. and Odicino, F. (2021). Current Treatment Options for Cervical Leiomyomas: A Systematic Review of Literature. Medicina Journal. 57(2): 92.
32. Lee, H. Lee, H. and Cho, Y. K. (2017). Cytokeratin7 and cytokeratin19 expression in high grade cervical intraepithelial neoplasm and squamous cell carcinoma and their possible association in cervical carcinogenesis. Diagn Pathol J. 12(1): 18.
33. Hrudka, J.; Rosová, B. & Halaška, M. J. (2020). Squamous cell carcinoma with sarcomatoid differentiation or carcinosarcoma of the uterine cervix associated with HPV33 infection: report of a rare case. Journal of Diagnostic Pathology. 15(1): 12.
34. Simona, S.; Park, K. J.; Kiyokawa, K.; Oliva, E.; McCluggage, W. G.; Soslow, R. A. (2021). Tumor Typing of Endocervical Adenocarcinoma: Contemporary Review and Recommendations From the International Society of Gynecological Pathologists. International Journal of Gynecological Pathology. 40(1): S75-S91.
35. Eni, A. O.; Ndukwe, C. O.; Olusina, D. B.; Nnakenyi, N. F.; Nzegwu, M. A.; Eluke, C. C.; Ukekwe, F. I.; Chiemeka, M. E., Aniume, I. O.; Nwokoro, O. C. (2023). Spectrum, Clinicopathologic Profile, and p16 Expression Pattern of Nonmalignant Cervical Tissues in Enugu, South-East Nigeria. Ibnosina J Med Biomed Sci 15(3): 121–128.
36. Maniar, K. P. and Wei, J-J. (2017). Pathology of Cervical Carcinoma. The Global Library of Women’s Medicine. Pp(1756-2228).
37. Turashvili. G. (2023). Cervix squamous cell carcinoma and variants. Pathology Outlines. Pp 72, 480.
38. Anant, M.; Singh, A.; Singh, V. Y. (2018). Papillary Squamotransitional Cell Carcinoma Cervix: Case Report of a Rare Variant Journal of South Asian Federation of Obstetrics and Gynaecology. 10(2): 429-431.
39. Yordanov, A.; Karaivanov, M.; Kostov, S.; Kornovski, Y.; Ivanova, Y.; Slavchev, S.; Todorova, V. and Vasileva-Slaveva, M. (2022). Papillary Squamotransitional Cell Carcinoma of the Uterine Cervix with Atypical Presentation: A Case Report with a Literature Review. Journal of Medicina (Kaunas). 58(12): 1838.
40. Rakesh, I. J.; Gupta, K.; Sinha, R. K. and Bhadani, P. P. (2019). Cotyledonoid dissecting leiomyoma: an uncommon form of a common disease. Obstet Gynecol Sci Journal. 62(5): 362-366.
41. Misugi, T.; Kitada, K.; Fudaba, M.; Tanaka, S.; Kurihara, Y.; Tahara, M.; Hamuro, A.; Nakano, A.; Koyama, M. and Tachibana, D. (2022). Preliminary outcomes of cervical cerclage for shortened cervix with decidual polyp. Healthcare Journal. 10(7): 1312.
42. Robert, J.; Lora, H. E. and Brigitte, M. R. (2019). Benign Diseasses of the Cervix. Blaustein’s Pathology of the Female Genital Tract. 7th ed.
43. Saha, S. S.; Chowdhury, R. R.; Mondal, N. R.; Roy, S. and Sengupta, S. (2017). Expression signatures of HOX cluster genes in cervical cancer pathogenesis: Impact of human papillomavirus type 16 oncoprotein E7. Oncotarget Journal. 30; 8(22): 36591–36602.
44. Yu, M.; Zhan, J. & Zhang, H. (2020). HOX family transcription factors: related signaling pathways and post-translational modifications in cancer. Journal of Cell Signal. 66(1): 109469.