| Objective:The gastric carcinoma is one of the most common malignant tumors in China. The morbidity and mortality are the highest in all kinds of the alimentary tract malignant tumors. At present, the happening and development of gastric cancer is still emphasis of study. On the clinic, although about 60% of patients with gastric carcinoma were treated validly, they died of tumor cells'the recurrence and metastasis. The happening and development of gastric cancer is a progress in which many factors, processes and various mechan- isms are involved. The activation of tumor suppressor gene and the deactivation of anti-oncogene are one of essential molecule mechanisms during these processes. There are three members of ras gene family, K-ras, H-ras and N-ras. The molecular mass of the protein they code is 21 kilodalton. So they are called p21 protein,p21ras,or Ras protein. Gene K-ras is one of ras gene family, and it fixes on the short arm of the 12th chormosome. The protein, which c-K-ras codes, is consisted of 189 amino acid .It can bind with guanosine triphosphate and have GTP enzyme's activity. C-K-ras distributes in intracyto- plasm, especially in facies medial of the cellular membrane.It is the main material in cell transmembrane signal transmission, and it can transmit outside signal into cells and take part in regulation system, which transmits cell multiplication signal, so that control cells'growth and differentiation. When ras gene is activated by carcinogenic agents, DNA is reprouducted uncontrolledly.The proient, which ras gene codes, interferes with cells'growth and differentiation progress by influencing transcription signal's transmission progress. That can make cell grown malignantly, and generate tumors or cancerate. Cathespin is a class of cysteine protienase in human being's normal cytolysosome. However, it expresses highly in malignant cells.Cathepsin B(CB) is a kind of capthin in mammalia animal and human being's cytolysosome. Some studies show that some endocrine cells, such as pancreatic gland and myocardial cells, also have CB. It is a kind of cysteine protein in cytolysosome, and it can degradate extracellular matrix, such as Laminin, Fibronetin, typeâ…£collagen and so on. Therefore it can destroy a series of tissue barrier and take part in tumors'soakage and transfusion.Nowadays, most studies on c-K-ras and capthepin B in gastric tumor are reported respectively, but studies on the relationship between them are rare. Therefore, in this study we detected the expressions of c-K-ras and CB in gastric carcinoma tissues, and normal gastric mucosa by S-P immunohistochemical technique, analyzed the correlations between the expressions of tumor cells, the correlations between the expressions and the biological behavior of gastric carcinoma. And We investigated its role in gastric tumor's happening, soakage and transfusion, staging and prognosis.Methods:In this study, we selected 73 samples of gastric carcinoma, 73 samples of normal gastric mucosa(>5.0cm)and 73 samples first station of regional lymph node. All patients had gastrectomy in the 4th hospital of HeBei Medical University from October 2005 to August 2006. All these samples were without chemotherapy or radiotherapy before surgery, which were proved adenocarcinoma by pathology. In this study, we used S-P immunohistochemical technique to detect the expre- ssions of protein c-K-ras and CB in gastric carcinoma tissues, normal gastric mucosa. The Correlations between the express- ions of c-K-ras and CB and the biological behavior of gastric carcinoma were analyzed, including patients'sex, age, tumor location, size, gross type, differentiation degree, the depth of invasion, and TNM stage etc. All statistical analyses were carried out with SPSS 13.0 and P<0.05 were considered significant.Results:1 The positive rates of c-K-ras were 43.84% in tissues of gastric carcinoma, which were significantly higher than the rates of 6.85% in normal gastric mucosa (P<0.05).2 The positive rates of CB were 42.47% in tissues of gastric carcinoma, which were significantly higher than the rates of 2.82% in normal gastric mucosa (P<0.05).3 In gastric carcinoma tissues, 49.20% of c-K-ras in gastric carcinoma tissue existed in the tumor bigger than 5.0cm, and the percentage was higher than 27.27% in the tumor smaller than 5.0cm, the comparison of the two does not show statistically significant (P=0.085>0.05). The expressions of c-K-ras in the group with infiltrating type (54.35%) were higher than localization type (25.93%, P<0.05), the expressions of c-K-ras in the group with poor differentiation (56.41%) were higher than well differentiation (29.42%, P<0.05), the expressions of c-K-ras in the group of T3+T4 (48.44%) were higher than T1+T2 (11.11%, P<0.05), the expressions of c-K-ras in the group with lymph node metastasis (59.09%) were higher than without lymph node metastasis (20.69%, P<0.05), the expressions of c-K-ras in the group ofâ…¢-â…£stage (58.70%) were significantly higher than group of I-â…¡stage (6.94%, P<0.05).4 In gastric carcinoma tissues, 50.98% of CB in gastric carcinoma tissue existed in the tumor bigger than 5.0cm, and the percentage was higher than 22.73% in the tumor smaller than 5.0cm. The comparison of the two shows significant difference (P<0.05) , the expressions of CB in the group with infiltrating type (54.35%) were higher than localization type (22.22%, P<0.05); the expressions of CB in the group with poor differentiation (43.60%) were significantly higher than well differentiation (41.18%, P=0.853>0.05), and there was no statistical significance, the expressions of CB in the group of T3+T4 (46.68%) were significantly higher than T1+T2 (11.11%, P<0.05), the expressions of CB in the group with lymph node metastasis (54.55%) were significantly higher than without lymph node metastasis (24.14%, P<0.05), the expressions of CB in the group ofâ…¢-â…£stage (54.35%) were significantly higher than group of I-â…¡stage (22.22%, P<0.05).5 No correlations were found between expre- ssion levels of c-K-ras in gastric carcinoma tissues and patients'sexes, ages and tumor size and locations. (P>0.05).And no correlations were found between expression levels of CB in gastric carcinoma tissues and patients'sexes, ages and tumor differentiation degrees, and locations. (P>0.05).6 A significant correlations were observed between the expression of c-K-ras and CB protein in gastric carcinoma tissues (rs= 0.263, P=0.024<0.05).Conclusion:1 The expressions of c-K-ras in gastric carcinoma tissues were higher than those in normal gastric mucosa. It shows the activation of c-K-ras participate the happening of gastric cancer. The expressions of CB in gastric carcinoma tissues were significantly higher than those in normal gastric mucosa. It shows the higher expressions of CB participate the happening of gastric cancer2 The expressions of c-K-ras in gastric carcinoma tissues become significantly higher along with differentiation degree to lower. The expressions of CB in gastric carcinoma tissues become significantly higher along with size to larger. The higher expression of c-K-ras and CB indicates the increase of gastric carcinoma's malignant degree. 3 The expressions of c-K-ras in gastric carcinoma tissues become significantly higher along with the depth of invasion to deeper, lymph node metastasis, TNM stage to higher. The expressions of CB in gastric carcinoma tissues become significantly higher along with the depth of invasion to deeper, lymph node metastasis, TNM stage to higher. The higher expression of c-K-ras and CB indicates the ability of invasion and metastasis of gastric carcinoma become higher. And the ability of tumor's invasion and metastasis reflect the prognosis, so the higher expression of c-K-ras and CB in gastric tumor shows poor prognosis indirectly.4 No correlations were found between expression levels of c-K-ras in gastric carcinoma tissues and patients'sexes, ages and tumor sizes,locations. No correlations were found between expression levels of CB in gastric carcinoma tissues and patients'sexes, ages , tumor locations and differentiation degree.5 In gastric carcinoma tissues, the expressions of c-K-ras and CB have positive correlation. It shows the expressions of c-K-ras and CB in gastric carcinoma may have the synergistic effect in happening, invasion and metastasis of gastric carcinoma.In conclusion, the abnormal expressions of c-K-ras in gastric carcinoma tissues play important roles in happening and development. And the disproportion expression of CB play important roles in invade and metastasis of gastric carcinoma and the prognosis of gastric carcinoma. Unite examining the expressions of c-K-ras and CB in gastric carcinoma can be useful in prognosticating the invasion and metastasis of gastric carcinoma, evaluating the prognosis of gastric carcinoma and guiding the reasonable comprehensive treatment.It can provide evidence for molecular biology stages in gastric carcinoma afterward.
|
PDF Full Text Request