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Muhammad Asghar Khan
Muhammad Imran
Reema Bughio
Yar Muhammad Jalbani
Tahir Muhammad Yaseen
Asim Shamim
Junaid Farooq
Usama Ahmed
Israr Khan
Izaz Khan


Colon adenocarcinoma, Diagnosis, Treatment


The study focuses on understanding the role of FBJ murine osteosarcoma viral oncogene homolog (FOS) expression and its regulatory mechanisms in colon adenocarcinoma (COAD). Analysis of FOS expression using the UALCAN dataset revealed a consistent down-regulation in cancerous cells compared to normal controls. Further exploration of FOS expression across various clinical parameters demonstrated significant down-regulation across different cancer stages, racial groups, genders, and age groups among COAD patients, suggesting its crucial role in tumor development. Validation of FOS expression using the GEPIA2.0 dataset confirmed its low expression in COAD tumors compared to normal samples. Additionally, validation analysis of FOS expression across different cancer stages showed dysregulation in all stages, with the highest expression in stage I and the lowest in stage IV. The study also investigated the promoter methylation level of FOS, revealing distinct methylation patterns across cancer stages, race groups, genders, and age groups, highlighting its association with COAD pathogenesis. Survival analysis using the KM plotter tool indicated a significant correlation between FOS expression levels and overall and disease-free survival (OS and RFS) in COAD patients, with lower FOS expression not associated with shorter survival times. Mutational analysis using the cBioPortal platform did not reveal any common alterations in COAD samples. These findings underscore the intricate role of FOS in COAD development, emphasizing its potential as a prognostic biomarker and therapeutic target in COAD management.

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1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021; 71: 209-249.
2. Usman M and Hameed Y. GNB1, a novel diagnostic and prognostic potential biomarker of head and neck and liver hepatocellular carcinoma. Journal of Cancer Research and Therapeutics 9000;
3. Usman M, Hameed Y and Ahmad M. Does epstein–barr virus participate in the development of breast cancer? A brief and critical review with molecular evidences. Biomedical and Biotechnology Research Journal (BBRJ) 2020; 4: 285-292.
4. Identification of Key Biomarkers for the Future Applications in Diagnostics and Targeted Therapy of Colorectal Cancer. Current Molecular Medicine 2022;
5. Chiarello MM, Fransvea P, Cariati M, Adams NJ, Bianchi V and Brisinda G. Anastomotic leakage in colorectal cancer surgery. Surg Oncol 2022; 40: 24.
6. Chargari C, Peignaux K, Escande A, Renard S, Lafond C, Petit A, Lam Cham Kee D, Durdux C and Haie-Méder C. Radiotherapy of cervical cancer. Cancer Radiother 2022; 26: 298-308.
7. Siegel RL, Miller KD and Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69: 7-34.
8. Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, Cercek A, Smith RA and Jemal A. Colorectal cancer statistics, 2020. CA Cancer J Clin 2020; 70: 145-164.
9. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A and Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut 2017; 66: 683-691.
10. [Kijima S, Sasaki T, Nagata K, Utano K, Lefor AT and Sugimoto H. Preoperative evaluation of colorectal cancer using CT colonography, MRI, and PET/CT. World J Gastroenterol 2014; 20: 16964-16975.
11. Dong Y, Wu X, Xu C, Hameed Y, Abdel-Maksoud MA, Almanaa TN, Kotob MH, Al-Qahtani WH, Mahmoud AM and Cho WC. Prognostic model development and molecular subtypes identification in bladder urothelial cancer by oxidative stress signatures. Aging 2024; 16: 2591-2616.
12. Hameed Y. Decoding the significant diagnostic and prognostic importance of maternal embryonic leucine zipper kinase in human cancers through deep integrative analyses. Journal of Cancer Research and Therapeutics 2023; 19: 1852-1864.
13. Ohhara Y, Fukuda N, Takeuchi S, Honma R, Shimizu Y, Kinoshita I and Dosaka-Akita H. Role of targeted therapy in metastatic colorectal cancer. World J Gastrointest Oncol 2016; 8: 642-655.
14. Watanabe T, Muro K, Ajioka Y, Hashiguchi Y, Ito Y, Saito Y, Hamaguchi T, Ishida H, Ishiguro M, Ishihara S, Kanemitsu Y, Kawano H, Kinugasa Y, Kokudo N, Murofushi K, Nakajima T, Oka S, Sakai Y, Tsuji A, Uehara K, Ueno H, Yamazaki K, Yoshida M, Yoshino T, Boku N, Fujimori T, Itabashi M, Koinuma N, Morita T, Nishimura G, Sakata Y, Shimada Y, Takahashi K, Tanaka S, Tsuruta O, Yamaguchi T, Yamaguchi N, Tanaka T, Kotake K and Sugihara K. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol 2018; 23: 1-34.
15. Wagner EF. AP-1--Introductory remarks. Oncogene 2001; 20: 2334-2335.
16. Durchdewald M, Angel P and Hess J. The transcription factor Fos: a Janus-type regulator in health and disease. Histol Histopathol 2009; 24: 1451-1461.
17. Chinenov Y and Kerppola TK. Close encounters of many kinds: Fos-Jun interactions that mediate transcription regulatory specificity. Oncogene 2001; 20: 2438-2452.
18. Hu H, Umair M, Khan SA, Sani AI, Iqbal S, Khalid F, Sultan R, Abdel-Maksoud MA, Mubarak A and Dawoud TM. 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: 432.
19. Fittall MW, Mifsud W, Pillay N, Ye H, Strobl A-C, Verfaillie A, Demeulemeester J, Zhang L, Berisha F and Tarabichi M. Recurrent rearrangements of FOS and FOSB define osteoblastoma. Nature communications 2018; 9: 2150.
20. van IJzendoorn DG, Forghany Z, Liebelt F, Vertegaal AC, Jochemsen AG, Bovée JV, Szuhai K and Baker DA. Functional analyses of a human vascular tumor FOS variant identify a novel degradation mechanism and a link to tumorigenesis. Journal of Biological Chemistry 2017; 292: 21282-21290.
21. Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi B and Varambally S. UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia 2017; 19: 649-658.
22. Tang Z, Kang B, Li C, Chen T and Zhang Z. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res 2019; 47: W556-W560.
23. Maciejczyk A, Szelachowska J, Czapiga B, Matkowski R, Hałoń A, Györffy B and Surowiak P. Elevated BUBR1 expression is associated with poor survival in early breast cancer patients: 15-year follow-up analysis. J Histochem Cytochem 2013; 61: 330-339.
24. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y, Reva B, Goldberg AP, Sander C and Schultz N. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2012; 2: 401-404.
25. Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R, Larsson E, Cerami E, Sander C and Schultz N. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 2013; 6: 2004088.
26. Wu D and Wang X. Application of clinical bioinformatics in lung cancer-specific biomarkers. Cancer Metastasis Rev 2015; 34: 209-216.
27. Abdel-Maksoud MA, Ullah S, Nadeem A, Shaikh A, Zia MK, Zakri AM, Almanaa TN, Alfuraydi AA, Mubarak A and Hameed Y. Unlocking the diagnostic, prognostic roles, and immune implications of BAX gene expression in pan-cancer analysis. American Journal of Translational Research 2024; 16: 63.
28. Liang Y, Diehn M, Watson N, Bollen AW, Aldape KD, Nicholas MK, Lamborn KR, Berger MS, Botstein D, Brown PO and Israel MA. Gene expression profiling reveals molecularly and clinically distinct subtypes of glioblastoma multiforme. Proc Natl Acad Sci U S A 2005; 102: 5814-5819.
29. Hanahan D and Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144: 646-674.
30. Huang L, Irshad S, Sultana U, Ali S, Jamil A, Zubair A, Sultan R, Abdel-Maksoud MA, Mubarak A and Almunqedhi BM. Pan-cancer analysis of HS6ST2: associations with prognosis, tumor immunity, and drug resistance. American Journal of Translational Research 2024; 16: 873.
31. He L, Deng HY and X CW. Decreased expression of MS4A12 inhibits differentiation and predicts early stage survival in colon cancer. Neoplasma 2017; 64: 65-73.
32. Liu W. Long non-coding RNA VPS9D1-AS1 promotes growth of colon adenocarcinoma by sponging miR-1301-3p and CLDN1. Hum Cell 2021; 34: 1775-1787.
33. [Ely HA, Mellon PL and Coss D. GnRH induces the c-Fos gene via phosphorylation of SRF by the calcium/calmodulin kinase II pathway. Mol Endocrinol 2011; 25: 669-680.
34. Riedel M, Berthelsen MF, Cai H, Haldrup J, Borre M, Paludan SR, Hager H, Vendelbo MH, Wagner EF and Bakiri L. In vivo CRISPR inactivation of Fos promotes prostate cancer progression by altering the associated AP-1 subunit Jun. Oncogene 2021; 40: 2437-2447.
35. Lambert SA, Jolma A, Campitelli LF, Das PK, Yin Y, Albu M, Chen X, Taipale J, Hughes TR and Weirauch MT. The human transcription factors. Cell 2018; 172: 650-665.
36. Kirch H-C, Flaswinkel S, Rumpf H, Brockmann D and Esche H. Expression of human p53 requires synergistic activation of transcription from the p53 promoter by AP-1, NF-κB and Myc/Max. Oncogene 1999; 18: 2728-2738.
37. Yoon KW, Byun S, Kwon E, Hwang S-Y, Chu K, Hiraki M, Jo S-H, Weins A, Hakroush S and Cebulla A. Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53. Science 2015; 349: 1261669.
38. Durchdewald M, Guinea-Viniegra J, Haag D, Riehl A, Lichter P, Hahn M, Wagner EF, Angel P and Hess J. Podoplanin is a novel fos target gene in skin carcinogenesis. Cancer Research 2008; 68: 6877-6883.
39. Debinski W and Gibo DM. Fos-related antigen 1 modulates malignant features of glioma cells. Molecular cancer research 2005; 3: 237-249.
40. [Debinski W and Gibo DM. Fos-related antigen 1 (Fra-1) pairing with and transactivation of JunB in GBM cells. Cancer biology & therapy 2011; 11: 254-262.
41. Ma K, Chang D, Gong M, Ding F, Luo A, Tian F, Liu Z and Wang T. Expression and significance of FRA-1 in non-small-cell lung cancer. Cancer investigation 2009; 27: 353-359.
42. Usui A, Hoshino I, Akutsu Y, Sakata H, Nishimori T, Murakami K, Kano M, Shuto K and Matsubara H. The molecular role of Fra‐1 and its prognostic significance in human esophageal squamous cell carcinoma. Cancer 2012; 118: 3387-3396.
43. Chiappetta G, Tallini G, De Biasio MC, Pentimalli F, de Nigris F, Losito S, Fedele M, Battista S, Verde P and Santoro M. FRA-1 expression in hyperplastic and neoplastic thyroid diseases. Clinical Cancer Research 2000; 6: 4300-4306.
44. Zhou H. Unveiling the unexplored novel signatures for osteoporosis via a detailed bioinformatics and molecular experiments based approach. American Journal of Translational Research 2024; 16: 1306-1321.
45. Luo M, Rehman A, Haque S, Izhar S, Perveen F, Haris M, Abdel-Maksoud MA, Saleh IA, Zomot N and Malik A. Thorough examination of the potential biological implications of the cuproptosis-related gene LIPT2 in the prognosis and immunotherapy in pan-cancer. American Journal of Translational Research 2024; 16: 940.

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