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The Expression of the Ratio of VEGF-C/VEGF-D CLIC1 and ECH1 in Gastric Carcinoma and Lymphatic Metastasis

Author: WangJingWen
Tutor: TangJianWu
School: Dalian Medical University
Course: Pathology and Pathophysiology
Keywords: The ratio of VEGF-C/VEGF-D CLIC1 ECH1 Gastric cainoma Lymphatic metastasis
CLC: R735.2
Type: Master's thesis
Year: 2011
Downloads: 39
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Abstract


Background: Metastasis is the most important biological characteristics of malignant tumor, at the same time, it is one of the fundamental causes of death of the patients who suffer from malignant tumors.As a common malignant gastroinstinal tumors ,gastric cancer has a strong ability of local invasion and distant metastasis.It main tansfers to the lymphatic in the early stage of metastasis .The extent and scope of lymph node metastasis play an important role in deciding prognosis. VEGF-C、VEGF-D are specific regulors of lymphangiogenesis.We had been pay more attention to the expression of VEGF-C and VEGF-D in gastric cancer of their own,but not pay much to the expression of the ratio of VEGF-C/VEGF-D in gastic cancer and metastasis and its relation to the lymphatic metastasis.There is no report in and abroad.Therefore,it is helpful to know more about the occurrence、development and mechanism of metastasis of gastric cancer to deeply study the relation ship between the ratio of VEGF-C /EGF-D and lymphatic metastasis which can also help to find the taget for the early detection of lymph node metastasis and prognosis. Our research team has engaged in the study about the mechanism of lymphatic metastasis of Hca-P and Hca-F which is a pair of syngenetic mouse hepatocarcinoma ascites cell lines which have different rates of lymphatic metastasis. We have picked out the lymphatic metastasis-associated genes in mouse hepatocarcinoma cell lines. The expressing level of CLIC1 and ECH1 are much higher in Hca-F than that in Hca-P cell lines in both mRNA and protein levels. Because there are the same origin of CLIC1、ECH1 proteins in the tissue of both human being and mouse,at the same time ,CLICS may local in the upstream of VEGF .Therefore, we have also study the relationships between CLIC1、ECH1and the ratio of VEGF-C/VEGF-D .Objective:1、To observe the different expression levels of the ratio of VEGF-C/VEGF-D、 CLIC1and ECH1 in normal gastric tissues、gastric carcinoma with lymph node metastasis negetive、gastric carcinoma with lymph node metastasis positive and lymph nodes of metastasis. To detection their roles in the occurrence、development and metastasis of gastric carcinoma.2、To observe the ratio of VEGF-C/VEGF-D、CLIC1 and ECH1 whether associated with clinicopathological factors such as sex、age、size of tumor、stage、histological type、differentiation and lymphatic metastasis positive or not.3、Study the relationship between the ratio of VEGF-C/VEGF-D and CLIC1、ECH1 to further explore the molecular pathways of the lymph node matastasis . Methods: The ratio of VEGF-C/VEGF-D、CLIC1and ECH1 are detected in 20normal gastric tissues、44 gastric carcinomas and 18 lymph nodes metastasis of gastric carcinoma by Inmunohistochemistry (IHC). We observed their relationship with some clinicopathological factors such as sex、age、size of tumor、stage、especially the histological type、differentiation and lymphatic metastasis positive or not. There are 33 adenocarcinoma (high differentiation 5cases、middle defferetiation17 cases、low differentiation 11 cases)、6 mucinous adenocarcinoma and 5 cases of signet ring cell carcinoma in 44cases gastric carcinoma;there are 23 cases with lymph node metastasis positive and 21 cases with lymph node metastasis negtive in44gastric carcinoma.RESULT:1.The expression of the ratio of VEGF-C/VEGF-D in the gastric carcinomaThe ratio of VEGF-C/VEGF-D in the normal tissues of gastric was 0.59±0.48,significantly lower than that in the gastric carcinoma with lymph node metastasis negetive 0.91±0.52 and the lymph nodes of metastasis 1.13±0.97 and the gastric carcinoma with lymph node metastasis positive 2.14±2.80(P<0.05).The ratio in positive group is significantly higher than in the negetive group(p<0.05).The ratio in tubular adenocarcinoma ,mucinous adenocarcinoma ,signet ring cell carcinoma are 1.72±2.39、1.00±0.69、1.15±1.13 respectively.But there is no significant among the three groups(p>0.05).The expression of the ratio in the high, medium and low differentiation groups of tubular adenocarcinoma are respectively 0.90±0.17、2.02±1.81和0.61±0.33.The difference between hight and medium differentiation group is significant (p<0.05);Also is the difference between medium and low differentiation groups.2.The expression of CLIC1 in the gastric carcinoma CLIC1The exression of CLIC1 in the normal tissues of gastric was 15471.90±18844.56,significantly lower than that in the gastric carcinoma with lymph node metastasis negetive 45837.57±32324.15、and the lymph nodes of metastasis 33416.93±25356.04 and the gastric carcinoma with lymph node metastasis positive29439.13±17430.89 (P<0.05). The expression in negetive group is significantly higher than in positive group(p<0.05).The expression in tubular adenocarcinoma, mucinous adenocarcinoma ,signet-ring cell carcinoma are 36339.89±28134.89、31709.72±16764.54 and 53824.82±25026.29,respectively.But there is no significant among the three groups(p>0.05).The expression of CLIC1 in the high, medium and low differentiation groups of tubular adenocarcinoma are respectively36393.69±20386.56、47317.93±32132.30、23631.67±16673.85,The difference between medium and low differentiation group is significant (p<0.05).3.The expression of ECH1 in the gastric carcinoma ECH1The exression of ECH1 in the normal tissues of gastric was 4113.31±3768.27 lower than that in the gastric carcinoma with lymph node metastasis negetive 9517.91±7151.79 and the lymph nodes of metastasis 7247.62±4743.59and the gastric carcinoma with lymph node metastasis positive14223.36±8106.63,but only the difference between the gastric carcinoma with lymph node metastasis positive and the normal tissues of gastric group is significantly in statistic. The expression of ECH1 is significantly higher in the gastric carcinoma with lymph node metastasis positive group than in the negtive group . The expression in tubular adenocarcinoma , mucinous adenocarcinoma,signet-ring cell carcinoma are 11366.69±8237.49、17512.88±3136.41 and 9367.13±8077.58 , respectively.The expression of ECH1 in mucinous adenocarcinoma is significantly higher than in the other two groups(p<0.05). The expression of ECH1 in the high, medium and low differentiation groups of tubular adenocarcinoma are respectively9248.25±8514.73、12217.15±7885.88 and 10545.46±8687.98,but there is no significant among the three groups(p>0.05)..4. The expressions of the ratio of VEGF-C/VEGF-D、CLIC1and ECH1 in sex、age、the size of tumor and stage groups are no significant difference.;there is negtive correlation between CLIC1 and the expression of the ratio of VEGF-C/VEGF-D in the gastric carcinoma with lymph node metastasis positive group . But the later group has no relation with the expression of ECH1.Conlutions:1.The increasingly expression of the ratio of VEGF-C/VEGF-D is significantly related with the lymphtic metastasis of gastric carcinoma,which may become an important indicator of lymphtic metastasis of gastric carcinoma .The changes of VEGF-C、VEGF-D may be an early event in lymphatic metastasisand VEGF-D contributes much more to the increasing of the ratio.The ratio of VEGF-C/VEGF-D is significantly associated with the differentiation degrees of gastric carcinoma2.The expression of CLIC1 in gastric carcinoma with lymph node metastasis negtive group is significantly higher than positive group which may have a negtive regulation in lymph node metastasis. The expression of CLIC1 is significantly associated with the differentiation degrees of gastric carcinoma.3.The expression of ECH1 in mucinous adenocarcinoma is the highest in adenocarcinoma proups which possibly be related to the histological pathological type of gastric carcinoma. ECH1may be one of the important genes to promote lymph node metastasis of gastric cancinoma .4.The expression of the ratio of VEGF-C/VEGF-D in the gastric carcinoma with lymph node metastasis positive group is negtive associated with CLIC1 which may indicate that the two indicators may affect lymph node metastasis .But the ratio in that group is not associated with ECH1.

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CLC: > Medicine, health > Oncology > Gastrointestinal Cancer > Gastric neoplasms
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