Dissertation
Dissertation > Medicine, health > Oncology > Respiratory system tumors > Lung tumors

The Expression of CD68 and c-Jun in Non-small Cell Lung Cancer

Author LiuZuo
Tutor WuYiMing
School Zhengzhou University
Course Occupational and Environmental Health
Keywords CD68 macrophage c-Jun AP-1 non-small cell lung cancer
CLC R734.2
Type Master's thesis
Year 2011
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It was in 1863 that Rudolf Virchow noted leucocytes in neoplastic tissues and made a connection between inflammation and cancer. He suggested that the " lymphoreticular infiltrate" reflected the origin of cancer at sites of chronic inflammation. Scholars in recent years pay attention to this old hypothesis again.Mono-macrophage infiltration is an indispensable component during the development of inflammation. A variety of proinflammatory cytokines secreted by mono-macrophages play crucial roles in the inflammatory microenvironment. The inflammatory microenvironment of tumors is characterized by the presence of host leucocytes both in the matrix surrounding and tumor tissue. Tumor-associated macrophages(TAM) are a major component of the infiltrates of most, if not all, tumors. Visible, macrophages are an important link between inflammation and tumor.Activator protein-1 (AP-1) is considered the "immediate early gene" and "early reaction proto-oncogene". In recent years, there are a large number of reports on AP-1 responding to various physiological or pathological signals, such as cytokines, growth factors in the inflammatory microenvironment, which directly or indirectly regulate the transcription of genes and the expression of protein about proliferation, differentiation, invasion, survival. Hagemann T reported that macrophages induced invasiveness of the MCF-7 human breast cancer cell line and the IGROV1 human ovarian cancer cell line via JNK/AP-1.This study detected the mRNA and protein expression level of CD68 (macrophage surface marker) and c-Jun(AP-1 subunit) in 67 cases of non-small cell lung cancer(NSCLC) samples including cancer tissues, adjacent tissues and normal tissues, to investigate their relationship with the development of NSCLC, and analyzed whether there was a link between macrophage counts and AP-1 in NSCLC to provide clinical clues for exploring their roles in the development of NSCLC. Materials and Methods67 cases of NSCLC samples including cancer tissues, adjacent tissues and normal tissue were collected from the First Affiliated Hospital of Zhengzhou Unicersity during the period from January,2008 to December,2009.Immunohistochemical SP method was used to detect the expression level of CD68 protein and c-Jun protein.The mRNA expression level of CD68 gene and c-Jun gene were detected by RT-PCR with GAPDH as references. One-Way Analysis of Variance and Student-Newman-Keuls were used to detect the statistical significance among groups. Spearman rank correlation coefficient method was used to investigate the relativity. Results were considered to be significant when the two-tailed p-value was less than 0.05.Results1 The protein expression level of CD68 and c-Jun in NSCLC samples including cancer tissues, adjacent tissues and normal tissuesCD68+cell number in cancer tissues, adjacent tissues and normal tissues was 97.49±2.54,52.14±1.85,11.78±1.37 respectively, and there was statistical significance between groups(F=31445.371,P<0.05). The mean optical density of c-Jun protein in cancer tissues, adjacent tissues and normal tissues was 0.25±0.03, 0.23±0.02,0.20±0.01, and there was statistical significance between groups (F=126.1,P<0.05). The CD68+cell counts in adjacent tissues was correlative with the TNM grade(F=158.273,P<0.05), lymph nodes metastases(F=84.985,P<0.05) and involvement of pleura(F=16.422, P<0.05). The expression of c-Jun in cancer tissues was correlative with the differentiation of lung cancer(F=18.002, P<0.05), TNM grade(F=11.668,P<0.05), lymph nodes metastases(F=13.061,P<0.05) and involvement of pleura(F=12.493,P<0.05). There was no correlation between CD68+ cell counts and the expression of c-Jun protein both in cancer tissues and normal tissues(P>0.05), and in adjacent tissues CD68+cell counts was correlative with the expression of c-Jun protein(r=0.519,.P<0.05). There was a positive correlation between CD68+cell counts in adjacent tissues and the expression of c-Jun protein in cancer tissues (r=0.410, P<0.05).2 The mRNA expression level of CD68 and c-Jun in NSCLC samples including cancer tissues, adjacent tissues and normal tissuesThe mRNA expression level of CD68 gene in cancer tissues, adjacent tissues and normal tissues was 0.31±0.20,2.01±0.25,1.30±0.26 respectively, and there was statistical significance between groups(F=852.249, P<0.05). The mRNA expression level of c-Jun gene in cancer tissues, adjacent tissues and normal tissues was 0.95±0.20,0.72±0.24,0.55±0.25, and there was statistical significance between groups(F=51.707, P<0.05). The mRNA expression level of CD68 gene in adjacent tissues was correlative with the TNM grade(F=77.695,P<0.05), lymph nodes metastases(F=48.372, P<0.05) and involvement of pleura(F=47.773,P<0.05).The mRNA expression level of c-Jun in cancer tissues was correlative with the differentiation of lung cancer(F=19.864, P<0.05), TNM grade(F= 101.840, P<0.05), lymph nodes metastases(F=55.920, P<0.05) and involvement of pleura(F=37.498, P<0.05). There was a positive correlation between the mRNA expression level of CD68 and that of c-Jun in cancer tissues(F=0.800, P<0.05), adjacent tissues(F=0.777, P<0.05) and normal tissues(F=0.903,P<0.05). There was a positive correlation between the mRNA expression level of CD68 in adjacent tissues and that of c-Jun in cancer tissues (r=0.729, P<0.05).ConclusionsMacrophages mainly infiltrated in tumor-adjacent tissues, and they may promote the development and metastasis of NSCLC by activating AP-1.

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