The Expression And Significance Of NF-κB,FAK And VEGF-C In Gastric Carcinoma

Background and Objective Gastric carcinoma is one of the most common malignant neoplasms in the world,it is also the primary cause of cancer death in our country.The invasion,metastasis and recurrence of carcinoma play a important role to the prognosis.It is known that the predominant dead reason depends on its invasive growth and metastasis in patients with gastric carcinoma.Focal adhesion kinase(FAK) plays a key role in regulating the attachment of tumor cells,which is important in the tumor's invasion and metastasis.It can activate the PI3K through FAK-PI3K signal pathway in the involvement of Ras,then make the downstream signal phosphorylation through the member of PKB,such as NF-κB,elevate the expression of bcl-2 which result in inhabiting the anoikis.Vascular endothelial growth factor(VEGF) mediates the proliferation of endothelial of lymphangion,and modulates the differentiation of endothelial of lymphangion and hyperplasia of lymphangion by VEGF/VEGFR signal,promoting lymphatic metastasis. It also can induce the phosphorylation of FAK inhabiting the apoptosis of tumor cell.By observing the expression of NF-κB,VEGF and FAK in gastric carcinoma,We try to explore their influence on tumor invasion and matastasis,their mutual relationship and the molecular mechanisms.Method The expression of NF-κBp65,VEGF-C and FAK were detected by Envision two-step immunohistochemical methods in paraffin-embeded sample from 78 cases of gastric carcinoma to analyze the correlation among NF-κBp65,VEGF-C and FAK and kinds of clinical factors(including sex,age,tumor size,histological type,deep extent of infiltrating,lymph node metastasis and distant metastasis).The adjacent gastric tissue(40 cases) served as a control group.We observed their expression to explore the influence on tumor invasion and matastasis, their mutual relationship and their possible molecular mechanisms,we analysised the relationship between the expression of NF-κBp65 and VEGF-C,NF-κBp65 and FAK,the clinicopathologic parameters of gastric carcinoma.Data were performed with SPSS 16.0 software. Chi-square test,fisher'exact test of probabilities and Spearman rank correlation were used,and Staticsly significant level was considered as "alpha equals 0.05".Result 1.The expression of NF-κBp65:(1)The expression of NF-κBp65 was detected in 58 of 78 gastric carcinoma(74.36%,58/78), which was significantly higher than those in normal gastric mucosa. (2)The expression of NF-κB in invasion to chorion(83.61%,51/61) was significantly higher than those invasion to low muscular layer(41.18%, 7/17).The expression of NF-κBp65 was detected in 41 of 47 gastric carcinoma with lymph node metastasis(87.23%,41/47).But 17 in 31 gastric carcinoma without lymph node metastasis(54.84%,17/31).The difference was significant(P＜0.05);And the expression of NF-κB with distant metastasis(85.37%,35/41)was significantly higher than those group without distant metastasis(62.16%,23/37).The difference was also significant(P＜0.05).(3)The expression of NF-κB has significant correlation to diferentiation,but it has no correlation to age,sex and tumor tissues(P＞0.05).2.The expression of VEGF-C:(1)The expression of VEGF-C was detected in 42 of 78 gastric carcinoma(53.85%,42/78),which was significantly higher than those in normal gastric mucosa;(2)The expression of VEGF-C was detected in 32 of 47 gastric carcinoma with lymph node metastasis(68.09%,32/47).But 10 in 31 gastric carcinoma without lymph node metastasis(32.25%,10/31),The difference was significant(P＜0.05).And the expression of VEGF-C with distant metastasis(65.85%,27/41) was significantly higher than those group without distant metastasis(40.54%,15/37).The difference were also significant(P＜0.05).(3)The expression of VEGF-C has significant correlation to diferentiation,but it has no correlation to age,sex and extent of invasion(P＞0.05).The expression of FAK:(1)The powerfully positive stain of FAK was detected in 42 of 78 gastric carcinoma(53.85%,42/78),which was significantly higher than those in normal gastric mucosa.(2)The expression of FAK in invasion to chorion(88.52%,54/61) was significantly higher than those invasion to low muscular layer(52.94%, 9/17).The expression of FAK was detected in 42 of 47 gastric carcinoma with lymph node metastasis(89.36%,42/47).But 21 in 31 gastric carcinoma without lymph node metastasis(32.26%,21/31).The difference was significant(P＜0.05).And the expression of FAK with distant metastasis(90.24%,37/41)was significantly higher than those group without distant metastasis(70.27%,26/37).The difference were also significant(P＜0.05).(3)The expression of FAK has significant correlation to diferentiation,but it has no correlation to age,sex(p＞0.05).3.The expression of NF-κB p65 has a positive correlation with that of VEGF-C ingastric carcinoma(rs=0.399,P＜0.05).NF-κB p65 also has a positive correlation with that of FAK ingastric carcinoma(rs=0.458,P＜0.001).Conclusion 1.The expression of NF-KB,VEGF-C and FAK in gastric carcinoma were significantly higher than those in normal gastric mucosa.There were significant correlation among them to the depth of invasion,lymph node metastasis and distant metastasis.Their play an important role in tumor invasion and metastasis.2.The extent expression of NF-KB,VEGF-C and FAK in gastric carcinoma have significant correlation to lymph node metastasis and distant metastasis.Detecting the expression of NF-KB,VEGF-C and FAK does good to predict an prognosis.The targeting treatment to NF-KB,VEGF-C and FAK may be one of the efficient means for suppressing tumor invasion and metastasis.