Expression And Clinical Significance Of Several Cell Senescence Markers In Colorectal Adenoma And Colorectal Cancer Tissue

Background:In our country,the morbidity and mortality of Colorectal cancer(CRC)is on the increase,which affects our health seriously.However,with early diagnosis and timely treatment of local CRC,the patients have an excellent prognosis,and the 5-year survival rate was over 90%.Nevertheless,the patients with metastatic or advanced colorectal cancer,has worst survival.The 5-year survival rate of these patients is only 11%[1,2].As we all know,the colorectal adenoma are recognized precancerous lesions.But we have no idea how these pre-malignant tumor progress to malignant invasive cancer.Therefore,to study the mechanisms or the pathogenesis of CRC,in favour of seeking the early diagnosis biology markers of CRC and finding the adenoma high risk of progressing to cancer,is beneficial to early prevent,diagnosis and treatment of CRC,which can improve the survival rate and reduce mortality.Studies have shown that cellular senescence is a tumor suppressor response that has been observed both in vitro and in vivo,and features of senescence have been documented in various human premalignant lesions,including melanoma,colon and lung adenoma,and others.We suspect that senescence may be involved in the process of the colorectal adenoma turning into cancer,and it needs further study.Aim:By detecting the expression of a number of cellular senescence markers in colorectal adenoma,colorectal cancer and colorectal normal tissue,we try to analyze the relationship between these cellular senescence markers and clinical data,so as to prove that senescence may be involved in the process of the colorectal adenoma turning into cancer.Then we can seek the possible biological markers in better estimation of risks of cancer progression,and to find a theoretical basis for the occurrence and development of CRC.Materials and methods:1.30 cases of paired colorectal adenoma and normal tissues?48 cases of paired colorectal cancer and normal tissue were stained by SA-?-gal.Through calculating the blue area ratio stained by SA-?-gal,so as to detect the senescent cells.Then we compared the expression of senescent cells in different colorectal tissue and analyse the relationship between the blue area ratio stained by SA-?-gal and clinical indicators(Pathological type,size,location,staging,lymph node metastasis,distant metastasis,etc.).2.We used immunohistochemical staining method to detecte the expression levels of p16INK4a and H3K9me3 in 30 cases of paired colorectal adenoma and normal tissues?48 cases of paired colorectal cancer and normal tissue and analyze the correlation with clinical index.3.Staistical analyses were performed using the SPSS 20.0 statistical software.The normal distribution of the measurement data were expressed as(mean�SD).The non normal distribution of measurement data were expressed as the median(four percentile interval).And the count data were expressed by frequency and percentage.The paired t-test,two-sample t-test,ANOVA,nonparametric Mann-Whitney test were used to analyse.Statistically significance was defined as P-value<0.05.Results:1.The blue area ratio stained by SA-?-gal of the colorectal adenoma tissue was bigger than the blue area ratio of the normal tissue adjacent to adenoma and colorectal cancer tissue(P<0.01).The blue area ratio of the colorectal cancer tissue was smaller than the normal tissue adjacent to cancer(P<0.01).By comparing different groups of the positive area ratio colorectal adenoma suggest that,tubular adenoma was bigger than villioustublar adenoma(P<0.01),the size of the colorectal adenoma<1cm was bigger than the size of the colorectal adenoma?1cm(P<0.01),progression free adenoma was bigger than advance adenoma(P<0.01),and the different positive area of colorectal adenoma with different gender,age,number and location was not statistically significant(P>0.05).By comparing different groups of the positive area ratio colorectal cancer suggest that,the moderately differentiated adenocarcinoma was bigger than low differentiated adenocarcinoma(P<0.01),No distant metastasis was bigger than distant metastasis(P<0.01),stage ?,?,? was bigger than stage IV(P<0.01),and the different positive area of colorectal cancer with different gender,age,location,depth of tumor invasion and and with or without lymph node metastasis was not statistically significant(P>0.05).2.The expression of p16INK4a in colorectal adenoma tissue was significantly higher than the colorectal cancer tissue and normal tissue adjacent to adenoma(P<0.01),and the expression of p16INK4a in the colorectal cancer tissue was significantly lower than normal tissue adjacent to cancer(P<0.05).In the colorectal adenoma,the different expression of p16INK4a of different pathological pattern,gender,age,size,number and location was not statistically significant(P>0.05).In colorectal cancer,the expression of p16INK4a of colorectal cancer without lymph node metastasis was higher than the colorectal with lymph node metastasis(P<0.05),and the expression of p16INK4a in the different stage was ?>?>?>?,and the different expression of p16INK4a of different gender,age,location,depth of tumor invasion and with or without distant metastasis was not statistically significant(P>0.05).3.The expression of H3K9me3 were highly expressed in colorectal adenoma and colorectal carcinoma(P<0.01).The expression of H3K9me3 showed no significantly correlation with the size,age,gender,location,pathological pattern of colorectal cancer and adenoma(P>0.05).Conclusion:1.The expression of SA-?-gal and p16INK4a in the colorectal adenoma tissue was higher than the colorectal cancer and the normal colorectal tissue.The different expression of these aging markers in the different colorectal tissue showed,the number of senescent cells in colorectal adenomas was more than the colorectal cancer.It indicated that that senescence may be involved in the process of the colorectal adenoma turning into cancer.2.The expression of SA-?-gal was low in the villioustublar adenoma,the colorectal adenoma with<lcm size,advance adenoma.And the expression of SA-P-gal was low in low differentiated adenocarcinoma,the colorectal with distant metastasis,the stage IV colorectal cancer.The result suggest that the adenoma high risk of progressing to cancer have less senescence cell.We suppose the detection of SA-?-gal may be a marker to find high-risk precancerous lesions.3.The expression of p16INK4a was high in the colorectal cancer without lymph node metastasis,stage ?,? colorectal cancer.The p16INK4a was supposed to.be as application indicating good prognosis.4.The expression of H3K9me3 was high not only in the colorectal adenoma,but also in the colorectal cancer,but also in the colorectal.It proved that H3K9me3 may be point out cell proliferation,even if it is detected in the tumor cell.