Expression Of Toll-like Receptor 4 And Nuclear Factor-kappab In Non-small Cell Lung Cancer And Its Clinical Significance

Background:Lung cancer, the most common human malignancy with a rapid growth, has been a serious threat to human health. Nearly half a century of lung cancer incidence and mortality rates has clear ascendant trend in developed countries, and the city is more obvious than in rural areas. In most large cities the incidence and mortality rates of lung cancer occupies the first or second position in malignant tumors. At present, many scholars for lung cancer biology conduct extensive research, but its pathogenesis is still unclear. In recent years, the inflammation of the effect of tumor growth has gained a lot of attention, at present more and more evidence proves that, in promoting tumors development and evolution, chronic infection and inflammation is thought to be the most important posteriority and environmental factor, and toll-like receptors mediated signaling pathways may play an important role. For instance, the up-regulation expression of toll-like receptors have a close relationship with gastric carcinoma, breast carcinoma and bowel cancer's growth and metastasis. Lung cancer is closely related to a kind of environmental exposure, and lung abnormal inflammatory has some relations with such disease.Toll-like receptor4, one of the important TLRs family members, plays an important role in natural immune systems. Nuclear factor-kappaB, widely existing in mammalian cells, is a kind of important transcription regulation factor, performs function of transcription factor, and activates transcription of cytokines associated with cells growth or apoptosis. TLR4-activating signaling pathway, like other members of TLRs, belongs to typical TLRs signaling pathway, can start NF-κB pathway and stress kinase pathway, then ultimately leads to inflammatory response. TLR4 is now found most associated with cancer incidence in TLRs family members, and many studies also show that NF-κB may participate in tumors development and metastasis. But it is needed to be studied whether both are expressed in non-small cell lung cancer tissue, their relevance, and whether they have relationship in the pathogenesis of lung cancer.Objective:This study was designed to investigate the protein expression of Toll-like receptor 4(TLR4) and nuclear factor-kappaB (NF-κB) in human normal lung tissues and non-small cell lung cancer (NSCLC) tissues, and analyse the relationship of TLR4 and NF-κB with various clinicopathological such as tumor's histological type, TNM stage, lymph node metastasis and toumor's differentiation degree. To explore the relationship between expression of TLR4 and NF-κB and oncogenesis development and clinical characteristic of lung cancer.Methods:In this study, Immunohistochemical SP methods were used to investigate the expression of TLR4 and NF-κB in 49 cases of NSCLC and 20 cases of paracancerous normal lung tissues. All the cases were used for routine histopathological diagnosis.Results:The positive rates of TLR4 and NF-κB protein were found 57.1%(28/49) and 69.4%(34/49) in NSCLC tissues, significantly higher than 15%(3/20) and 10%(2/20) in 20 cases of paracancerous normal lung tissues (P<0.05). The expression of TLR4 and NF-κB in NSCLC tissues was no relationship with patient's age, gender, smoking, TNM stage and lymph node metastasis (P>0.05). But TLR4 expression had a close relationship with tumor's differentiation degree of NSCLC (P<0.05). The expression of NF-κB in adenocarcinoma was stronger than in Squamous cell carcinoma (P<0.05). The expression of TLR4 was positively correlated with the expression of NF-κB (P<0.05).Conclusions:Abnormality great expression of TLR4 and NF-κB in NSCLC tissues and the expression of TLR4 was positively correlated with the expression of NF-κB, the expression of TLR4 are associated with with tumor's differentiation degree, the more malignancy, and the more expression of TLR4, the expression of NF-κB in adenocarcinoma was stronger than in Squamous cell carcinoma. All these may hint that TLR4 and NF-κB may play an important role in the progression and development of NSCLC,which may provid a new pathway for research pathogenesy of lung cancer.