The Expression And Clinical Significance Of TLR4?NF-?B And Ki-67 In Colorectal Cancer

Research background and Objective:Colorectal cancer(CRC)is one of the most frequent malignant tumors of the digestive system.Colorectal cancer ranks third among males and second among females in the incidence of various malignant tumors worldwide.In 2012,1.36 million new cases of colorectal cancer were diagnosed worldwide,and colorectal cancer has become the third most common malignant tumor.With the development of China's economy,the incidence of colorectal cancer in China is increasing year by year.The incidence and mortality of colorectal cancer are currently ranked in the forefront of malignant tumors in China,ranking behind gastric and esophageal tumors.However,the etiology of colorectal cancer is quite complex,and may be involved in the process of canceration by multiple factors and steps.Traditional treatments such as surgery,radiotherapy and chemotherapy are not very effective in the treatment of colorectal cancer.Therefore,it is crucial to deeply exploring the specific mechanism of the occurrence and development of colorectal cancer.We know that uncontrolled proliferation is one of the important biological behaviors of cancer cells.Abnormal regulation of cell division cycle and excessive proliferation will lead to tumorigenesis.Many studies have confirmed that the active proliferation of tumor cells is closely related to the occurrence,development and adverse prognosis of tumors.Therefore,it is crucial to searching for mechanisms related to the regulation of tumor proliferation activity for the early diagnosis and treatment of colorectal cancer.TLR4 is one of the important members of Toll-like receptors,which can be activated by lipopolysaccharide(LPS)and further stimulates downstream Nuclear Factor-?B(NF-?B),ultimately promoting the release of inflammatory cytokines.In recent years,it has been found that the sustained activation of TLR4-mediated inflammatory signaling pathway can also regulate the proliferation of cancer cells.Although many studies have reported that activation of TLR4 signaling pathway can promote the abnormal proliferation of liver cancer,breast cancer,pancreatic cancer and other malignant tumors.However,the effect of TLR4/NF-?B pathway on the proliferation of colorectal cancer is not yet clear.On the one hand,TLR4/NF-?B pathway can inhibit the proliferation of tumor cells by inducing anti-tumor immunity.On the other hand,it can also promote the growth of cancer cells by secreting a variety of cytokines.In this study,the expression of TLR4 and NF-?B in colorectal cancer was detected with immunohistochemical IHC method.Ki-67 was used as an index to evaluate the proliferative activity of colorectal cancer.The aim of this study is to further demonstrate the effects of TLR4 and NF-?B on the proliferation of colorectal cancer and the interaction between them,so as to provide a new therapeutic target for the prevention and treatment of colorectal cancer.Methods: This study retrospectively analyzed 68 patients information with colorectal cancer hospitalized in the Department of Gastrointestinal Surgery,Affiliated Hospital of Southwest Medical University from June 2017 to June 2018.The clinical data of selected patients are well preserved.No adjuvant therapies such as radiotherapy,chemotherapy and biotherapy were performed before the operation,and all the tissue specimens of the patients after the operation were confirmed by pathological examination.Another 30 specimens of carcinoma tissues(the distance between para-carcinoma tissues and carcinoma tissues should be more than 5 cm)were selected as control group.Immunohistochemical IHC method was used to stain 68 carcinoma tissues and 30 para-carcinoma tissues.Finally,we detected the expression of TLR4,NF-?B and Ki-67 in carcinoma tissues and para-carcinoma tissues,and analyzed their correlation with clinicopathological data.Results:The expression rates of TLR4,NF-?B and Ki-67 protein in carcinoma tissues were 69.11%(47/68)?60.29 %(41/68)and 72.05%(49/68),which significantly higher than those in the para-carcinoma tissues were 16.7%(5/30)?26.67%(8/30)and 20.00%(6/30)(P<0.05).The expression of TLR4,NF-?B and Ki-67 was significantly related with the CEA,degree of differentiation,depth of invasion,lymph node metastasis and TNM stage(P<0.05),but there was not relationship with the gender,age,initial symptoms and location of tumors(P > 0.05).The expression of TLR4 and Ki-67 were positively correlated(r= 0.511,P<0.05)in colorectal carcinoma.The expression of TLR4 and NF-?B were positively correlated(r=0.649,P<0.05)in colorectal carcinoma.The expression of NF-?B and Ki-67 were positively correlated(r=0.496,P<0.001)in colorectal carcinoma.According to whether TLR4 and NF-?B were positive,68 patients with colorectal cancer were further divided into TLR4(+)NF-?B(+)group,TLR4(+)NF-?B(-)group,TLR4(-)NF-kappa B(+)group,TLR4(-)NF-kappa B(-)group,and TLR4(-)NF-kappa B(-)group.Our results showed that the Ki-67 average labeling index(LI)in TLR4(+)NF-?B(+)group was significantly higher than that in the TLR4(+)NF-?B(-)group(P<0.05),the TLR4(-)NF-?B(+)group(P < 0.05),and TLR4(-)NF-?B(-)group(P < 0.05).Conclusion:1?The high expression of TLR4 and NF-?B in colorectal cancer is related to the biological characteristics of colorectal cancer,indicating that they may play an important role in the occurrence and development of colorectal cancer.2?With the increase of TLR4 and NF-kappa B expression,the proliferative activity of colorectal cancer also increased significantly,suggesting that both TLR4 and NF-kappa B can promote the proliferation of colorectal cancer.3?TLR4 is positively correlated with the expression of NF-kappa B.Refer to some recent research reports,it is speculated that TLR4 may promote the proliferation of tumors by activating downstream NF-kappa B after activation,and cause the occurrence and malignant progression of colorectal cancer.Its specific mechanism needs further study.