| Colorectal cancer (CRC) is one of the most common gastrointestinaltumor, ranking third in cancer incidence, fifth in mortality, which shows anincreasing trend. Despite constantly continuously updated drugs and treatment,long-term survival of colorectal cancer has not been significantly improved,mainly for the unclear development mechanism.Insulin-like growth factor(IGFs) are important factors to promote mitosis in vivo, with a strong effect ofproliferation and anti-apoptosis. Current study showed that over expression ofIGFs, found in human breast cancer, colorectal cancer, stomach cancer,ovarian cancer and other tumors, is involved in cell transformation andmetastasis.In recent years, a series of studies have shown that the abnormalexpression of IGFs play an important role in the formation and developmentof malignant tumors. Among T2DM patients, the expressions of IGFs areabnormally high in both blood circulation and tissues, which may promotetumor in turn. In this study, a combination of detections of expression ofIGF-1, IGF-1R, IGFBP-3in both CRC patients and in CRC patients withT2DM was used to observe the relationship between T2DM and thedevelopment of CRC and to explore the relationship between the expression ofIGFs and the promotion,invasion and metastasis of the CRC. We hope we canachieve such goals: on the one hand to provide new biological indicators todetermine malignancy and evaluate prognosis of CRC, on the other handprovide a new target for treatment to the patients of CRC with T2DM andprovide a theoretical basis of treatment for patients with T2DM.Objective:To observe the expression of IGF-1, IGF-1R, IGFBP-3in the CRC and in the CRC with T2DM and to analyze the relationship between the expressionof the three and T2DM in order to study the expression and clinicalsignificance of IGF-1, IGF-1R, IGFBP-3in CRC. Through exploring therelationship between T2DM and development of CRC to achieve such goals:on the one hand to provide new biological indicators to determine malignancyand evaluate prognosis of CRC, on the other hand provide a new target fortreatment to the patients of CRC with T2DM and provide a theoretical basis oftreatment for patients with T2DM.Method：The expression of IGF-1, IGF-1R, IGFBP-3was detected in61casesT2DM-CRC group,122cases of simple CRC group,22cases normalcolorectal mucosa group and39cases normal colorectal mucosa withoutT2DM group by immunohistochemical method. We analyze the correlationbetween the expression and clinical significance of IGF-1, IGF-1R andIGFBP-3based on the result above and the pathological features of CRC.Result：1.1Expression of IGF-1、IGF-1R and IGFBP-3in the solely CRC groupand the relation between the expression and the pathological featuresThe expression rate of IGF-1(54.1%) in cancer tissues was significantlyhigher than that in normal mucosa of colorectal (25.6%), the difference wasstatistically significant (P<0.05);The expression rate of IGF-1R (63.9%) incancer tissues was significantly higher than that in normal colorectal mucosa(20.5%), the difference was statistically significant (P<0.05);The expressionrate of IGFBP-3(73.0%) in cancer tissues was significantly lower than that innormal colorectal mucosa (100.0%), the difference was statistically significant(P<0.05).The expression of IGF-1has correlation with the depth of invasion, TNMstage and lymph node metastasis in CRC(P<0.05), but has nothing to do withother factors (P>0.05).Expression of IGF-1in CRC with late TNM stage, deepinvasion, lymph node metastasis were significantly higher compared with thecontrol group, the difference was statistically significant (Table2). The expression of IGF-1R and IGFBP-3both have correlations with TNM stageand lymph node metastasis in CRC (P<0.05), but have nothing to do withother factors (P>0.05). Expression of IGF-1R in CRC with late TNM stage,lymph node metastasis were significantly higher compared with the controlgroup, the difference was statistically significant. On the contrary, expressionof IGFBP-3were significantly lower compared with the control group, thedifference was statistically significant.2Expression of IGF-1、 IGF-1R and IGFBP-3in the T2DM-CRC groupand the relation between the expression and the pathological featuresThe expression rate of IGF-1(72.1%) in cancer tissues was significantlyhigher than that in normal mucosa of colorectal (40.9%), the difference wasstatistically significant (P<0.05); The expression rate of IGF-1R (80.3%) incancer tissues was significantly higher than that in normal colorectal mucosa(36.4%), the difference was statistically significant (P<0.05); The expressionrate of IGFBP-3(88.5%) in cancer tissues was higher than that in normalcolorectal mucosa (86.4%), but the difference was no statistically significant(P <0.05).The expression of IGF-1in T2DM-CRC group has correlation with thedepth of invasion, TNM stage and lymph node metastasis in T2DM-CRC(P<0.05), but has nothing to do with other factors (P>0.05).Expression ofIGF-1in T2DM-CRC with late TNM stage, lymph node metastasis wassignificantly higher compared with the control group, the difference wasstatistically significant. The expression of IGF-1R have correlations with thedepth of invasion, TNM stage,lymph node metastasis and remote metastasis inT2DM-CRC(P<0.05), but have nothing to do with other factors(P>0.05).Expression of IGF-1R in T2DM-CRC with deep invasion, late TNMstage, lymph node metastasis and remote metastasis was significantly highercompared with the control group, the difference was statistically significant.The expression of IGFBP-3in T2DM-CRC group has correlation withhistological stage and remote metastasis in T2DM-CRC (P<0.05), but hasnothing to do with other factors (P>0.05).Expression of IGFBP-3in T2DM-CRC with low histological stage and remote metastasis wassignificantly higher compared with the control group, the difference wasstatistically significant.3Effect of high concentration of blood glucose on the expression ofIGF-1, IGF-1R and IGFBP-3in CRCThe expression rate of IGF-1(72.1%) in T2DM-CRC tissues wassignificantly higher than that in solely CRC tissue(54.1%), the difference wasstatistically significant (P<0.05).On the congtrary, its expression rate in thecolorectal mucosa with T2DM group (40.9%) and normal colorectal mucosa(25.6%) had no significant difference, showing no statistical significance(P>0.05). The expression rate of IGF-1R (80.3%) in T2DM-CRC tissues wassignificantly higher than that in solely CRC tissue(63.9%), the difference wasstatistically significant (P<0.05).On the congtrary,its expression rate in thecolorectal mucosa with T2DM group (36.4%) and normal colorectal mucosa(20.5%) had no significant difference,showing no statistical significance(P>0.05).The expression rate of IGFBP-3(88.5%) in T2DM-CRC tissues wassignificantly higher than that in solely CRC tissue (73.0%), the difference wasstatistically significant (P<0.05).Its expression rate in the colorectal mucosawith T2DM group (86.4%) was lower than that in normal colorectal mucosa(100%) had no significant difference, showing a significance of threshold(P=0.043), which remained to be further studied.4Correlation between different factors and different tissueCorrelation analysis showed that: In122cases of solely CRC tissues, theexpression of IGF-1and that of IGFBP-3or IGF-1R were both negativelycorrelated (P<0.05, P<0.05); IGF-1expression and IGF-1R expression werepositively correlated (P<0.05); In61cases of T2DM-CRC group, theexpression of IGFBP-3and IGF-1or IGF-1R expression showed nocorrelation (P>0.05, P>0.05); while the expression of IGF-1R and IGF-1displayed a significant positive correlation (P<0.05). In the total183cases ofCRC, the expression of GFBP-3and that IGF-1and IGF-1R also showed a significant negative correlation (P<0.05, P<0.05); IGF-1expression andIGF-1R expression were positively correlated (P<0.05).Conclusions：1. IGF-1, IGF-1R and IGFBP-3may be involved in the occurrence anddevelopment of both the CRC and the IGF-1, IGF-1R is a factor to promotetumorigenesis, whereas IGFBP-3may be a protective factor in tumorigenesis.2. IGF-1, IGF-1R and IGFBP-3involved in the invasion and metastasisin CRC. IGF-1and IGF-1R plays a synergistic effect therein, whereasIGFBP-3plays a antagonistic effect therein.Combined detection of the expression of IGF-1, IGF-1R, IGFBP-3in theCRC, might be determined to the clinical malignancy, prognosis andmonitoring for cancer andsupply a new biological target.3. IGF-1R mediated abnormality signaling pathway may plays animportant role in T2DM increasing the occurrence of CRC process, andIGFBP-3shows a protective effect.Thus, in the treatment of patients with T2DM-CRC, the high selectivitytarget drug for IGF-1R and IGFBP-3migt be one of the effective treatment inthe CRC clinical treatment... |
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