| Objective:Diabetes mellitus is one of the most common diseases in the world,which seriously affects the systemic metabolic function.In recent decades,the global incidence of diabetes has increased significantly.Persistent hyperglycemia can lead to damage and dysfunction of various organs(kidney,heart,fundus,blood vessel or nerve).The relationship between diabetes mellitus,especially type 2 diabetes mellitus(T2DM),and tumorig-enesis has attracted widely attention in academic circles.Colorectal cancer(CRC)is a common malignant tumor in China,and its incidence is increasingly year by year.Previous studies have found that the incidence of colorectal cancer in type 2 diabetes mellitus was higher than that in the general population.However,the possible mechanism remains unclear.High mobility group box 1(HMGB1)is a chromatin protein whose content is rank second to histone in eukaryotic cells,and it plays important roles in regulating gene transcription and gene repair.The expression of HMGB1 in various tumors had been proved to be increased.Receptor for advanced glycation end product(RAGE)is one of the members of immunoglobulin superfamily in cell surface molecule,and it is the only receptor of HMGB1.The combination of RAGE and HMGB1 has high affinity and can participate in the proliferation,invasion and metastasis of many kinds of cancer cells.RAS protein is a low molecular weight protein,which comes from G protein family.It is a recognized proto-oncogene that inhibits apoptosis.RAS network is huge and complex,and it is functioned by many connecting pathways.Moreover,previous studies uncovered that HMGB1-mediated RAGE activation led to Yap1 accumulation in a Ras-dependent mechanism in CRC cells.Insulin-like growth factor-1(IGF-1)is an important mitogenic factor in vivo,which plays an important role in promoting proliferation and inhibiting apoptosis.Current studies have found that IGF-1 and its receptor IGF1R are highly expressed in human breast cancer,colorectal cancer,gastric cancer and other malignant tumors.Further studies have found that they are related to cell transformation and metastasis of malignant tumors.Ras/Raf/MEK/MAPK-ERk can be used as the downstream pathway of IGF-1,and its activation can promote the occurrence and development of tumors.In this study,the expression of RAGE,HMGB1,IGF1R and RAS in colorectal cancer and colorectal cancer cmbined with type 2 diabetes mellitus was studied by immunohistochemical method.The effect of type 2 diabetes mellitus on the expression of these factors was analyzed,and the relationship between the expression of RAGE,HMGB1,IGF1R and RAS and clinicopathological characteristics of colorectal cancer was analyzed.Methods:Immunohistochemical Elivision TM plus two-step method was used to study the expression of RAGE,HMGB1,IGF1R and RAS in 30 cases of colorectal cancer and 29 cases of colorectal cancer combined with type 2diabetes mellitus.The relationship between RAGE,HMGB1,IGF1R and clinicopathological characteristics and the interaction between them were analyzed.SPSS16.0 software was used for statistical analysis.?~2 test,Fisher exact probability method and correlation analysis were used for data analysis.Results:1 Immunohistochemical staining of RAGE protein1.1 RAGE protein expression in CRC group and CRC with T2DM groupRAGE protein was positioned in the cytoplasm.21 cases of colorectal cancer were positive,and the positive rate was 70%.In 21 cases of colorectal cancer combined with diabetes,the positive expression rate was 72.4%.There was no significant difference in RAGE positive expression rate between the two groups(P=0.838).1.2 Clinical and pathological significance of RAGE protein expression in CRC and CRC with type 2 diabetes mellitusThere was no correlation between RAGE expression and age,sex,differentiation degree,tumor size,invasion depth and lymph node metastasis in the two groups(P>0.05).2 Immunohistochemical staining of 2 HMGB1 protein2.1 Expression of HMGB1 protein in CRC group and CRC with T2DM groupThe positive reaction of HMGB1 protein was localized in nucleus and/or cytoplasm.14 cases of colorectal cancer were positive,the positive rate was46.7%.The positive expression rate of HMGB1 in 17 cases of colorectal cancer combined with T2DM was 58.6%.There was no significant difference in the positive expression rate of HMGB1 between the two groups(P=0.358).2.2 Clinicopathological significance of HMGB1 protein expre-ssion in colorectal cancer and colorectal cancer combined with type 2 diabetes mellitusThe expression of HMGB1 was not correlated with age,sex,differentiation degree,tumor size,invasion depth and lymph node metastasis in the two groups(P>0.05).3 Immunohistochemical staining of 3 IGF1R protein3.1 Expression of IGF1R protein in CRC group and CRC with T2DM groupThe positive reaction of IGF1R protein was localized in cytoplasm.10cases of colorectal cancer showed positive expression,the positive expression rate was 33.3%.19 cases of colorectal cancer combined with T2DM showed positive expression,the positive expression rate was 65.5%.The expression of IGF1R protein in colorectal cancer with diabetes was significantly higher than that in colorectal cancer with diabetes(P=0.013).3.2 The clinicopathological significance of the expression of IGF1R protein in CRC and CRC withT2DMThere was no significant correlation between IGF1R expression and age,sex,differentiation degree,tumor size,invasion depth and lymph node metastasis in the two groups(P>0.05).4 Immunohistochemical staining of RAS protein4.1 RAS protein expression in CRC group and CRC with T2DM groupThe positive reaction of RAS protein was localized in cytoplasm.11cases of colorectal cancer showed positive expression,the positive expression rate was 36.7%.In 19 cases of colorectal cancercombined with type 2 diabetes,the positive expression rate was 65.5%.The expression of RAS protein in the latter group was significantly higher than that in the former group(P=0.027).4.2 Clinical and pathological significance of RAS protein in CRC and CRC combined with T2DM group.The expression of RAS in colorectal cancer group and colorectal cancer with type 2 diabetes mellitus group was both not correlated with age,sex,differentiation degree,tumor size,invasion depth and lymph node metastasis(P>0.05).5 The relationship between RAGE,HMGB1,IGF1R and RAS expression in CRC group and CRC combined withT2DM group.The expression of RAGE and HMGB1 was positively correlated in colorectal cancer combined with type 2 diabetes mellitus group(r=0.578,P=0.003),but not in colorectal cancer(P=0.236).The expression of IGF1R and RAS was positively correlated in colorectal cancer combined with type 2diabetes mellitus group(r=0.479,P=0.017),but not in colorectal cancer group(P=0.108).While the expression of RAGE and RAS were not correlated in both the two groups(P=0.419,P=0.197).Conclusion:1.The expression of IGF1R and RAS at protein level in CRC with T2DM was significantly increased,while there was no differences in the expressions of RAGE and HMGB1 in CRC between those with or without T2DM.2.The expression of IGF1R and RAS in CRC with T2DM was positively correlated,suggesting that IGF1R/RAS pathway may play a more significant role in the development of colorectal cancer with diabetes mellitus. |
PDF Full Text Request