Hexokinase - Ii Expression Status In Colorectal Cancer Tissues

Background and ObjectiveColorectal cancer is one of the most regular malignant tumor in our country, the incidence rate goes up year by year along with the uprising of living standard and the alteration of living habit. The five year survival rate of colorectal cancer after radical operation still have no obvious improvement although the emerging of different combined therapy aiming directly at cancer. The most common metabolic hallmark of malignant tumors is their propensity to produce energy through glycolysis even in the presence of oxygen, this is because of hypoxia enviroment and the unusual expression of glycometabolism enzymes.Clinical researches showed that glycolysis is active in colorectal cancer. Hexokinase is the key enzyme regulating cell glycolysis and catalyzing the essential irreversible first step of the glycolytic pathway. Through this step glucose is phosphorylated and turned to glucose-6-phosphate (G-6-P) as essential energy and carbon source for cancer cells. Mammalian tissues have four hexokinase isoforms designated as HK-Ⅰ,HK-Ⅱ,HK-Ⅲand HK-Ⅳ. HK-Ⅱis the major hexokinase isoform expressed in cancers. The expression of HK-Ⅱwere increased in many kinds of malignant tumor tissue. Now HK-Ⅱis one of the most popular research sites for anti-turmous targeted therapy. My experiments studied the expression of HK-Ⅱin colorectal cancers using immunohistochemistry method, and analyized the relationships between HK-Ⅱexpression and the clinical features of colorectal cancer patients such as tumor sizes, clinical stages, cell differentiation levels, and remote metastatic situations.MethodsWe checked the expression of HK-II in 114 colorectal cancer tissue and 114 adjacent negative cutting edge tissue using immunohistochemistry technique and analyzed experiment pictures using ImagePro software.Then we further investigated the relationships between HK-Ⅱexpression and the clinical features of colorectal cancer patients such as tumor sizes,clinical stages, cell differentiation levels, remote metastatic situation. ResultsThe HK-Ⅱlocates inside cell plasm and show Sulfur-Crested to Buffy color particle after immunohistochemistry dying, while nucleus does not show any staining. In 114 cancer tissue,82 showed positive dying, the positive rate was 71.9%, while in 114 negative cutting edge tissue only 11 showed positive dying, the positive rate was 9.6%, with a P value of 0.000. After analyzed the experiment pictures of the two tissues using ImagePro software system, we found the IOD/area in cancer tissue was 121.89±18.57 compare to 142.35±21.30 in normal colorectal mucosa, the difference between these two tissues has statistical significance, with a P value of 0.003, which indicated that the cancer tissue had more positive staining particle than normal colorectal mucosa tissue. In 21 cancer tissue with tumors small than 2.0cm in diameter, only 6 showed positive staining, the positive rate was 28.6%, while 76 showed positive staining in 93 turmor tissue large than 2.0cm in diameter, the positive rate was 84.2%, with a P value of 0.000.In 18 patients with poorly differentiated tumors,17 showed positive dying, with a positive rate of 94.4%; In 74 patients with moderately differentiated turmors 55 showed positive dying, with a positive rate of 74.3%;In 22 patients with well differentiated tumors 10 showed positive dying, with a positive rate of 45.5%,the inter-group P value was 0.002, showed significantl statistics difference.In 56 lymph node metastasis patients 44 showed positive dying, with a positive rate of 78.6%, while in 58 non-lymph node metastasis patients 38 showed positive dying, with a positive rate of 65.5%.The P value between two groups was 0.121.In 26 hepatic metastasis patients 22 showed positive dying, with a positive rate of 84.6%, while in 88 non-hepatic metastasis patients 60 showed positive dying, with a positive rate of 68.2%. The P value between two groups was 0.101.In 13 Dukes A patients 7 showed positive dying, with a positive rate of 53.8%. In 38 Dukes B patients 25 showed positive dying, with a positive rate of 65.8%. In 36 Dukes C patients 27 showed positive dying, with a positive rate of 75.0%. While in 27 Dukes D patients 23 showed positive dying, with a positive rate of 85.2%, the inter-group P value was 0.149. In 51 Dukes A+B patients 32 showed positive dying, with a positive rate of 62.7%, while in 63 Dukes C+D patients 50 showed positive dying, with a positive rate of 79.4%, the P value between two groups was 0.05.Conclusions The expression of HK-Ⅱincreased significantly in colorectal cancer tissue than normal colorectal mucosa tissue.The positive expression of HK-Ⅱin colorectal cancer correlated well with turmor size, cell differentiation level and tumor staging as well.