الفهرس 
TitleOnly 14 pages are availabe for public view
 |  | from | 111 |  |  |
| | | from | 111 | | |
Abstract
Colorectal cancer is the 6th cancer in Egypt, representing 4% of the total cancers and 53% of GIT cancers. The gold standard for CRC detection is colonoscopy. CRC is common among Egyptian patients undergoing colonoscopy, its incidence ranges 10.6-14%. However, the majority of patients are diagnosed only at advanced stages.
Even though there is progress in the treatment of CRC using surgery, chemotherapy and radiotherapy, but they are associated with multiple side effects and complications. New therapeutic approaches such as immunotherapy and targeted therapy are being explored as alternative treatments. One of the prerequisites for the development of efficient cancer immunotherapy approaches is the identification of tumor specific antigens, including cancer testis (CT) antigens. Approximately 250 genes encode CT antigens. Their restricted normal tissue distribution but distinctive expression in multiple malignancies makes them possible tumor markers and attractive immunotherapeutic targets.
Sperm associated antigen 9 (SPAG9) gene is a CTA gene, located on the 17q21.33, which has a specific expression in acrosomal compartment of the sperm and participates in spermatozoa-egg interaction. It also functions a scaffolding protein that bring MAPKs and their target transcription factors. F-box protein 39 (FBXO39) is another CTA gene, located on 17p31.1. which belongs to the F-box family. FBXO proteins are important parts of the SCF (Skp1Cul1-F-box protein) type E3 ubiquitin ligase complex entailed in detection and recruitment of substrates for ubiquitination which has been reported to be associated with oncogenesis and cancer progression.
The present study aimed to measure mRNA expression levels of 2 cancer testis antigen genes: SPAG9 and FBXO39 in 50 primary colon cancer (CC) patients. Determination of the association of their expression with the clinicopathological criteria, in particular the location of tumour and the extent or metastasis of the tumour was also done.
To all patients, detailed history was taken. Computed tomography on the abdomen and pelvis was done to assess tumour location, size, regional lymph node involvement and distant metastasis. Patients treated by previous chemo or radiotherapy or having other malignancies were excluded from the study. Colonoscopy was done to evaluate mass location, size, shape and characteristics and tissue biopsies were taken from tumor tissue and adjacent non tumor tissue. Biopsies were used for histopathological examination and molecular studies. Histopathological examination was performed to confirm the diagnosis of colon cancer and evaluate type and grading of the tumour.
RNA was extracted from tumor tissue and adjacent non tumor tissue, followed by quantitative real time polymerase chain reaction using SYBR Green DNA binding dye and primers specific for SPAG9 and FBXO39. Relative expression of genes was calculated by comparative Cq method.
The study included 50 primary CC patients, 31 (62%) were females and 19 (38%) were males (ratio 1.6:1), with an age range from 23 to 80 years and a median age of 57 years. Left sided tumors were found in 66% of them. Almost all of the cases (96%) were adenocarcinomas and most of them (70%) were stage III.
Summary & Conclusion
70
The relative gene expression of SPAG9 was increased in tumor tissue compared to adjacent normal tissue but this increase did not reach the level of statistical significance. On the other hand, SPAG9 showed a significant increase in large sized tumors compared to smaller size tumors. SPAG9 appears to have an emerging role in tumorigenesis through its role in MAPK pathway. It may promote growth, metastasis, and drug resistance of tumors. It also modulates cell cycle progression and upregulates matrix metalloproteinases during the progression of tumors.
Our results revealed a significant increased expression of FBXO39 in tumor tissue compared to normal adjacent tissue. This may be attributed to the role of FBXO39 as important component of the SCF type E3 ubiquitin ligase complex entailed in detection and recruitment of substrates for ubiquitination which has been reported to be associated with oncogenesis and cancer progression. But the diagnostic performance of FBXO39 was not satisfactory. There was no significant association between FBXO39 relative gene expression and the studied clinicopathological variables.
In conclusion, our work pinpoints the importance of two members of CT antigens. The introduction of tumor antigens and immune response in management of cancer is still in its early stages. Now that immunotherapy revolution has started and promising results are clear in a variety of cancers, further studies are warranted to clarify the role of CT antigens in cancer diagnosis and therapy.