Correlation Of Transforming Growth Factor-Beta, SMAD4 Associate Molecule And Cellprolifetous In Colonrectal Carcinoma

Aims: Colon-rectal carcinoma is a familiar malignant tumor, and its incidence is ascending year by year in recent years. Along with the development of tumor molecular biology research, and the cognition to colon-rectal carcinoma's molecular level gradually thorough, we know tumor occurs because of the abnormity of cell division, and it is also a cell life cycle disease. DNA prolifetous may post the variety of cell period, and give a explanation to the cancerization of colon-rectal carcinoma. About how cell period abnormality occurs, "intracellular signal transduction" has become the widespread concerned biological question recently. Intracellular signal transduction turns to lead biology behaviors such as growth, development, division and death etc., and closely relates to the occurrence and development of malignant tumor, such as colon-rectal carcinoma. Until now we have already discovered at least 4 signal transduction thoroughfares related to the evolvement of colon-rectal,namely WNT/Wingless thoroughfare, k-ras thoroughfare, the TGF-β thoroughfare and p53 thoroughfare .The TGF-β thoroughfare, mediated by the SMAD, is of them .This research will carry on a thorough study about the relation between colon-rectal carcinoma DNA prolifetous and TGF-β, Smad4 partner molecular.Material and method: All cases were obtained from the gastro-intestinal surgery department of Shandong Provincial Hospital, and their clinical and pathology reports were recorded. Among them males 44, females 25; ≤ 50 years old is 27, >50 years old 42; colon cancer is 23, rectal cancer 46; the Dukes staging: stage A 14, stage B17, stage C 31, and stage D 7. Another 37 normal colon-rectal mucosa were collected as control. We use the method of RT-PCR and FCM, detect the level of TGF-β mRNA and the DNA concentration, and use the SPSS11.0 for windows statistics software to carry on One-Way ANOVA analysis towards unitizing number variable by checking each clinical data and pathologic specimen. The data were all expressed with ± S.D.; and the relation of two variable was adopted a straight line related analysis. Result:1. In the 37 normal colon-rectal mucosa, 8 expressed TGF-β positive, whose positive rate was 21.62%; and in the 69 carcinoma tissue, 42 expressed positive, the positive rate 60.84%. Two group have significant difference (x²=14.88, P<0.01). The gray scale of TGF-β mRNA in normal tissue is 0.94 ±s 0.38, and in the carcinoma tissue is 1.14 ± 0.40 , the difference between them was also significant (t=3.2, P< 0.05). In the normal tissue, the corresponding gray scale of TGF-β mRNA in the 24 rectum mucous is 0.74±0.23, and in the 13 colon mucous 0.96±0.37, the difference was also significant (t=2.08, P<0.05).In the 37 normal tissue, 27 expressed TβRII positive, the positive rate was 72.97%; and in the 69 carcinoma tissue, 28 expressed positive, the positive rate 40.59%. Two group have significant difference (x²=17.91, P<0.01). The gray scale of TβRII mRNA in normal tissue is 1.07 ±s 0.27, and in the carcinoma tissue is 0.95 ±0.23, the difference between them was also significant(t=2.29, P<0.05).In the 37 normal tissue, 32 expressed Smad4 positive, the positive rate was 86.48%; and in the 69 carcinoma tissue, 43 expressed positive, the positive rate 62.31%. Two group have significant difference (x²=6.80, P<0.05) The gray scale of Smad4 mRNA in normal tissue is 1.10 ±s 0.32, and in the carcinoma tissue is 0.93 ±0.28, the difference between them was also significant (t=2.76, P<0.05).2. The expression of TGF-β , T β RII, Smad4 was independent of the age, sex, position of the patients (P>0.05). Smad4 was correlated with the size, differentiation of the tumor (P>0.05); TβRII was correlated with differentiation of the tumor (P> 0.05 ); and the expression of TGF-β , T β RII, Smad4 was also correlated with the soakage depth, lymphoid transfer or not and Dukes stage of the tumor (P>0.05). TGF-β has a higher expression in the patients with deep soakage, lymphatic metastasis, later Dukes Stage; T β RII has a higher expression in the patients with higher differentiation, superficial soakage, no lymphatic metastasis, and later Dukes Stage. Smad4 has a higher expression in the patients with higher differentiation, tumor size<5cm, superficial soakage, no lymphatic metastasis, and earlier Dukes Stage.3. In the 69 carcinoma patients, 16 cases expressed both TGF-β and T β RII positive; 15 cases expressed both TGF-β and T β RII negative; TGF-β and T β RII have no relativity (Mantel-Haenszel x²=0.28, P=0.6). 27 cases expressed both TGF-β and Smad4 positive; 11 cases expressed both TGF-β and Smad4 negative; TGF-β and Smad4 have no relativity (Mantel-Haenszel x²=0.18, P=0.67). 25 cases expressed both T β RII and Smad4 positive; 23 cases expressed both T β R II and Smad4 negative; T β RII and Smad4 have no relativity (Mantel-Haenszel x2=14.59, P<0.05).4. To evaluate the cell multiplication, we used SPF, PI, DI, G_0/1, G₂M etc. as index. TGF-β has nothing correlated with SPF, PI, DI, G_0/1, G₂M (r_SPF=0.207, r_PI=0.115, r_DI=0.261, r_G0/1=0.185, r_G2M =0.197; P>0.05); T β RII has nothing correlated with SPF, PI, DI, G_0/1, G₂M (r_SPF=-0.193, r_PI=-0.078, r_DI=-0.109, r_G0/1= -0.211, r_G2M =-0.178; P>0.05); Smad4 has no relativity with DI (r_DI=-0.216, P>0.05), but negative relativity with SPF, PI, G_0/1, G₂M (r_SPF=-0.305, r_PI=-0.293, r_G0/1=-297, r_G2M =-0.320; P<0.05).Conclusion:1. TGF-β was rarely expressed in normal colon-rectal mucosa tissue, but over expressed in colon-rectal carcinoma tissue. T β RII and Smad4 were higher expressed in normal tissue than the carcinoma tissue.2. The expression of TGF-β , T β RII, Smad4 was independent of the age, sex, position of the patients. Smad4 was correlated with the size, differentiation of the tumor; TβR II was correlated with differentiation of the tumor; and the expression of TGF-β , T β RII, Smad4 was also correlated with the soakage depth, lymphoid transfer or not and Dukes stage of the tumor.3. TGF-β and the T β RII have no relativity; TGF-β and Smad4 to have no relativity; the T β RII and Smad4 present positive relativity.4. TGF-β has nothing correlated with SPF, PI, DI, G_0/1, G₂M; T β RII has nothing correlated with SPF, PI, DI, G_0/1, G₂M; Smad4 has no relativity with DI, but negative relativity with SPF, PI, G_0/1, G₂M .5. TGF-β can be one of the early diagnosis index of colon-rectal carcinoma; by examine the dosage of TGF-βmRNA in the blood, we may diagnose colon-rectal carcinoma in the early stage.