ジャーナル・オブ・オンコロジーの研究と治療

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Prognostic Role of H3K9 Methyltransferase G9a and Sprouty 1 in Colorectal Carcinoma

Haggag R, Khairy DA, Mahmoud AS, Harb OA, Salem RA, Abdel hafez MN, Habib FM and Gertallah LM

Background: Despite recent advances in the treatment of both early and advanced colorectal cancer, it remains the second leading cause of cancer deaths in the western world. G9a-dependent H3K9 methylations (G9a) have been shown to mediate epigenetic silencing of several tumours suppressor genes including DSC3, MASPIN, and CDH1. Sprouty1 (SPRY1) appears to act as a tumour suppressor in cancer, whereas we demonstrated that SPRY2 functions as a putative oncogene in colorectal cancer.
Methods: The clinic pathological correlation of G9a and S SPRY 1 Immuno-histochemical expression was assessed in tumour specimens of paraffin blocks retrieved from 50 colorectal carcinoma patients.
Results: Our patients included 30 men and 20 women, with a median age of years 57 (range, 29 80 years). Adenocarcinoma represented in 45 (90%) patients. Of the 50 patients, G9a was highly expressed in 56% (28/50) patients and 54% (27/50) patients had high expression of SPRY 1. The high expression of G9a in CRC was significantly correlated with the tumour size, grade, stage, presence of lymph node, distant metastases (p<0.001 for all), and tumour site (p=0.002), No significant correlation was found between G9a expression and age or sex of our patients. For SPRY1, high expression was negatively correlated with the tumour size, presence of lymph node metastases (p<0.001 for both), stage (p=0.002), and presence of distant metastases (p=0.03). No significant correlation was found between SPRY1 expression, age, sex, grade, and size or tumour site. After a median follow up of 32 (range; 8-35) months, patients with low G9a expression had significant higher median TDP than those with high expression (p<0.001). In controversy, patients with high SPRY1 expression had significant higher TDP (p<0.001). 2-Year OS of patients with low G9a expression was significantly higher than those with high expression (100% vs. 49.5%, respectively; p<0.001). For SPRY 1 expression; patients with high expression had significant higher 2-year OS rate (100% vs. 38.3%; respectively; p<0.001). Patients with combined low G9a and high SPRY 1 1expression had the highest TDP and OS rate.
Conclusion: Assessment of Sprouty-1 and G9a expression markers can be considered as useful promising prognostic markers for CRC patients. Value of combination of both markers could be considered in future studies.