EXPLORING THE ROLE OF TP53 IN KIDNEY RENAL CLEAR CELL CARCINOMA (KIRC): EXPRESSION ANALYSIS, PROMOTER METHYLATION, AND SURVIVAL ANALYSIS AND MUTATIONAL ANALYSIS THROUGH BIOINFORMATICS TOOLS
Main Article Content
Keywords
MAPK1, Cancer, Biomarker, Prognosis, UALCAN, TCGMA, KM plotter, cBioPortal, LUAD, EGFR
Abstract
In this study we focus on the expression, promoter methylation, mutation analysis and overall survival of MAPK1 gene in lung adenocarcinoma (LUAD) patients with the help of bioinformatics tools. Firstly the expression pattern of MAPK1 was analyzed in patient sample and compare with control group. The consequences showed that gene of interest are crucially down regulated in LUAD patient as compare to control group. Then to verify the result the expression of targeted gene was analyzed on the basis of other pathological attributes for example stages of life, sex, ethnicity and phases of cancer. Remarkable deviation of MAPK1 gene expression was detected in LAUD sample versus normal samples which emphasizes the pathological importance of gene expression in LUAD patients. When we analyzed the promoter methylation of MAPK1 gene in LUAD patients versus normal group a slight hypo methylation was found that shows the epigenetic regulation of target gene. Subsequently KM plotter tool was used to analyze the overall survival (OS) rate of patient with the expression of MAPK1 gene in LUAD sample in contrast to normal samples and found that overall good survival with low expression of the target gene. Mutation analysis of MAPK1 gene in LUAD sample by cBioPortal disclose that little genetic variation cause little dis-functioning of the gene. MAPK1 gene analysis point up the urgency of target gene as therapeutic and prognostic indicator in treatment of LUAD patients.
References
2. Heymach, J., et al., Clinical cancer advances 2018: annual report on progress against cancer from the American Society of Clinical Oncology. Journal of Clinical Oncology, 2018. 36(10): p. 1020-1044.
3. Debela, D.T., et al., New approaches and procedures for cancer treatment: Current perspectives. SAGE open medicine, 2021. 9: p. 20503121211034366.
4. Yasir, M., et al., Anti-bacterial activity of essential oils against multidrug-resistant foodborne pathogens isolated from raw milk. Brazilian Journal of Biology, 2022. 84: p. e259449.
5. Hameed, Y. and S. Ejaz, TP53 lacks tetramerization and N-terminal domains due to novel inactivating mutations detected in leukemia patients. Journal of Cancer Research and Therapeutics, 2021. 17(4): p. 931-937.
6. Usman, M., Y. Hameed, and M. Ahmad, Does human papillomavirus cause human colorectal cancer? Applying Bradford Hill criteria postulates. ecancermedicalscience, 2020. 14.
7. Bray, F., et al., Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 2024. 74(3): p. 229-263.
8. Nicholson, B.D., et al., The Suspected CANcer (SCAN) pathway: protocol for evaluating a new standard of care for patients with non-specific symptoms of cancer. BMJ open, 2018. 8(1): p. e018168.
9. Travis, W.D., Pathology and genetics of tumours of the lung, pleura, thymus, and heart. (No Title), 2004: p. 344.
10. Travis, W.D., et al., International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. Journal of thoracic oncology, 2011. 6(2): p. 244-285.
11. Herbst, R.S., D. Morgensztern, and C. Boshoff, The biology and management of non-small cell lung cancer. Nature, 2018. 553(7689): p. 446-454.
12. Fujiwara, A., et al., Bilateral ovarian metastasis of non-small cell lung cancer with ALK rearrangement. Lung Cancer, 2014. 83(2): p. 302-304.
13. Fujiwara, K., et al., Clinical implications of metastases to the ovary. Gynecologic oncology, 1995. 59(1): p. 124-128.
14. Yada-Hashimoto, N., et al., Metastatic ovarian tumors: a review of 64 cases. Gynecologic oncology, 2003. 89(2): p. 314-317.
15. Miller, P.C., et al., A novel mapk–microrna signature is predictive of hormone-therapy resistance and poor outcome in er-positive breast cancer. Clinical cancer research, 2015. 21(2): p. 373-385.
16. Burotto, M., et al., The MAPK pathway across different malignancies: a new perspective. Cancer, 2014. 120(22): p. 3446-3456.
17. Grossi, V., et al., p38α MAPK pathway: A key factor in colorectal cancer therapy and chemoresistance. World journal of gastroenterology: WJG, 2014. 20(29): p. 9744.
18. Wang, W., et al., MicroRNA profiling of follicular lymphoma identifies microRNAs related to cell proliferation and tumor response. haematologica, 2012. 97(4): p. 586.
19. Du, L., et al., CD44-positive cancer stem cells expressing cellular prion protein contribute to metastatic capacity in colorectal cancer. Cancer research, 2013. 73(8): p. 2682-2694.
20. Erkutlu, I., et al., Correlation between Rho-kinase pathway gene expressions and development and progression of glioblastoma multiforme. Tumor Biology, 2013. 34: p. 1139-1144.
21. Kaushik, S., et al., A tyrosine kinase protein interaction map reveals targetable EGFR network oncogenesis in lung cancer. bioRxiv, 2020: p. 2020.07.02.185173.
22. Zhang, Z.-y., et al., CircRNA_101237 promotes NSCLC progression via the miRNA-490-3p/MAPK1 axis. Scientific Reports, 2020. 10(1): p. 9024.
23. Maciejczyk, A., et al., Elevated BUBR1 expression is associated with poor survival in early breast cancer patients: 15-year follow-up analysis. J Histochem Cytochem, 2013. 61(5): p. 330-9.
24. Dong, Y., et al., Prognostic model development and molecular subtypes identification in bladder urothelial cancer by oxidative stress signatures. Aging, 2024. 16(3): p. 2591-2616.
25. Chandrashekar, D.S., et al., UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia, 2017. 19(8): p. 649-658.
26. Maciejczyk, A., et al., Elevated BUBR1 expression is associated with poor survival in early breast cancer patients: 15-year follow-up analysis. Journal of Histochemistry & Cytochemistry, 2013. 61(5): p. 330-339.
27. Yoshizawa, A., et al., Impact of proposed IASLC/ATS/ERS classification of lung adenocarcinoma: prognostic subgroups and implications for further revision of staging based on analysis of 514 stage I cases. Modern pathology, 2011. 24(5): p. 653-664.
28. Cerami, E., et al., The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer discovery, 2012. 2(5): p. 401-404.
29. Dong, Y., et al., Prognostic model development and molecular subtypes identification in bladder urothelial cancer by oxidative stress signatures. Aging (Albany NY), 2024. 16(3): p. 2591.
30. Jia, B., et al., Prognostic roles of MAGE family members in breast cancer based on KM-Plotter Data. Oncol Lett, 2019. 18(4): p. 3501-3516.
31. Hu, H., et al., CDCA8, a mitosis-related gene, as a prospective pan-cancer biomarker: implications for survival prognosis and oncogenic immunology. American Journal of Translational Research, 2024. 16(2): p. 432.
32. Abdel-Maksoud, M.A., et al., Unlocking the diagnostic, prognostic roles, and immune implications of BAX gene expression in pan-cancer analysis. American Journal of Translational Research, 2024. 16(1): p. 63.
33. Andrade, C., The P Value and Statistical Significance: Misunderstandings, Explanations, Challenges, and Alternatives. Indian Journal of Psychological Medicine, 2019. 41(3): p. 210-215.
34. Yen, C.Y., et al., DNA methylation, histone acetylation and methylation of epigenetic modifications as a therapeutic approach for cancers. Cancer Lett, 2016. 373(2): p. 185-92.
35. Society, A.C., Cancer and the poor: a report to the nation, 1989, American Cancer Society Atlanta, GA.
36. Freeman, H.P., Cancer in the socioeconomically disadvantaged. CA: A Cancer Journal for Clinicians, 1989. 39(5): p. 266-288.
37. Freeman, H.P., Cancer in the economically disadvantaged. Cancer, 1989. 64(S1): p. 324-334.
38. McQueen, A., et al., Risk perceptions and worry about cancer: does gender make a difference? Journal of health communication, 2008. 13(1): p. 56-79.
39. WHO, G., International statistical classification of diseases and related health problems. 1992.
40. Group, U.C.S.W., United States cancer statistics: 1999–2010 incidence and mortality web-based report. Atlanta: US Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute, 2013. 201.
41. Usman, M., et al., Breast cancer risk and human papillomavirus infection: a Bradford Hill criteria based evaluation. Infectious Disorders-Drug Targets (Formerly Current Drug Targets-Infectious Disorders), 2022. 22(4): p. 41-50.
42. Mao, J., et al., [Retracted] Risk Factors for TERT Promoter Mutations with Papillary Thyroid Carcinoma Patients: A Meta‐Analysis and Systematic Review. Computational and Mathematical Methods in Medicine, 2022. 2022(1): p. 1721526.
43. Dunlop, M.G., et al., Cancer Risk Associated with Germline DNA Mismatch Repair Gene Mutations. Human Molecular Genetics, 1997. 6(1): p. 105-110.
44. Gao, J., et al., Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal. Science Signaling, 2013. 6(269): p. pl1-pl1.
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.
Muhammad Afzal
Department of Biochemistry, Faisalabad Medical University, Faisalabad, Pakistan.
Inayatullah Mirani
Livestock / Animal Husbandry Shaheed Benazir Abad, Pakistan.
Nargis Janyaro
Shaheed Benazir Bhutto University of Veterinary and Animal Science Sakrand, Pakistan.
Syed Sabir Ali Shah
Livestock and Fisheries Department, Government of Sindh, Pakistan.
Abdullah Sethar
Livestock Breeding Services Authority (LBSA) Sindh, Livestock & Fisheries Department, Government of Sindh, Pakistan.
Imtiaz Ali Soomro
Peoples University of Medical and Health Science Nawabshah, Pakistan.
Tamseel Saleem
Department of Biochemistry and Physiology, Faculty of Animal Husbandry and Veterinary Sciences (AHVS), Sindh Agriculture University, Tandojam, Pakistan.
Kashif Prince
Department of Medicine, Cholistan University of Veterinary & Animal Sciences, Bahawalpur, Pakistan.
Muhammad Kashif Iqbal
Institute of Continuing Education & Extension, Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan.
Muhammad Kaleem
Institute of Continuing Education and Extension, Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan.
Aqsa Mustafa
Department of Biochemistry, Islamia University of Bahawalpur, Pakistan.
Habibullah Janyaro
Department of Veterinary Surgery, SBBUVAS, Sakrand, Pakistan.