Expression Of MACC1, SIRT1 And MTA3 In EGJA And Its Relationship With Clinical Pathological Factors Related To Tumor Invasion And Prognosis

Background:Esophagogastric junction adenocarcinoma (EGJA) is a cancer that occurs at the junction of the esophagus and stomach. In the past decades, the incidence of EGJA significantly increased, especially in developed countries such as Europe and the United States, the incidence increased by 2.5 times compared to 1970s. In recent years, the incidence of EGJA in our country is also showing a rising trend. To date, in the middle and late stage of esophageal gastric junction adenocarcinoma clinical use of surgical resection is the main treatment, postoperative adjuvant radiotherapy or chemotherapy to strengthen the efficacy, the effect is not ideal. Compared with distal gastric cancer and esophageal cancer, EGJA has special biological behavior, high malignancy and poor prognosis. The 5-year survival rate (5-YS) is less than 20%. Thus it tends to be classified as an independent type of tumor. Most of EGJA patients eventually died of tumor recurrence and metastasis.. For many years, in view of the limitation of the traditional treatment methods, many scholars have focused on the research of EGJA in the diagnosis and treatment of tumors. There are few studies on Biological indicators of prognosis in patients. To investigate the expression of metastasis-associated in colon cancer-1(MACC1), silent information regulator 1(SIRT1), metastasis associated protein3 (MTA3) in esophagogastric junction adenocarcinoma and adjacent tissues, then analysis of the correlation between them and tumor invasion and clinicopathological parameters, in the end we discuss its relationship with patients’prognosis.Methods:Collect archive wax blocks to made paraffin tissue microarrays (TMA) and use immunohistochemical SP-9001 three-step method to detect the expression of MACC1, SIRT1, MTA3 in 65 cases of esophagogastric junction adenocarcinoma and adjacent tissues. SPSS23.0(Statistical package for social sciences) software is used to analyze the expression of MACC1, SIRT1, MTA3 in esophagogastric junction adenocarcinoma and adjacent tissues, the correlations among these indicators, the relationship between them and the clinicopathological parameters(gender, age, tumor size, tumor location, depth of invasion, vascular invasion, perineural invasion, lymph node metastasis, lymph node positive number, distant metastasis, pathological type, pathological grades, TNM staging) survival analysis and prognosis of 65 patients with esophagogastric junction adenocarcinoma.Results:1. MACC1 in EGJA tissue expression positive in 55 cases, the positive rate is 85% (55/65) and in adjacent tissues expression positive in 25 cases, the positive rate was 38% (25/65) and expression of MACC1 in EGJA was significantly higher than that of normal tissue beside carcinoma (X2=29.25, P= 0.000, P< 0.05).2. SIRT1 in EGJA tissue expression positive in 50 cases, the positive rate is 77% (50 /65) and in adjacent tissues expression positive in 27 cases, the positive rate was 42% (27/65). The expression of SIRT1 in EGJA was significantly higher than that of normal tissue beside carcinoma (X2=16.85, P= 0.000, P< 0.05).3. MTA3 in EGJA organization expression was positive in 23 cases, the positive rate is 35% (23/65), and in the adjacent tissues expression positive in 52 cases, the positive rate was 80% (52/65) and expression in EGJA MTA3 was significantly higher than that of normal tissue beside carcinoma (X2=26.50, P= 0.000, P< 0.05).4. The expression of MACC1 in EGJA tissue was divided into 2 groups, the positive group and the negative group. Positive group (55 cases),1-YS was 74.5%.,3-YS was 40.7%,5-YS was 20.2%, the average survival time for 39.042 months. The median survival time was 23 months; negative group (10 cases),1-YS was 90%.3-YS was 81.3%,5-YS was 66.8%, the average survival time for 64.700 months. The median survival time was 43 months. Univariate survival analysis showed that the survival time of the positive group was significantly shorter (X2=5.724, P=0.017, P< 0.05)..5. The expression of SIRT1 in EGJA tissue was divided into 2 groups, the positive group and the negative group. Positive group (50 cases),1-YS for 70% of,3-YS for 40.7% of that 5-YS 20.2%, the average survival time for 36.309. The median survival time for 22 months; negative group (15 cases),1-YS was 93.3%,3-YS was 73.3%, 5-YS was 52.6%, the average survival time for 61.267 months. The median survival time for 36 months. Univariate survival analysis showed that the survival time of the positive group was significantly shorter (X2=5.226,P=0.022, P< 0.05).6. The expression of MTA3 in EGJA tissue was divided into 2 groups, the positive group and the negative group. Positive group (23 cases),1-YS (95.7%),3-YS for 87% of that 5-YS 80.2%, the average survival time for 69.942. The median survival time for 45 months; negative group (42 cases),1-YS was 66.7%.,3-YS was 26.2%,5-YS was 21.2%, the average survival time for 26.090 months. The median survival time for 19 months. Univariate survival analysis showed that the survival time of the positive group was significantly shorter (X2=23.706, P=0.000, P< 0.05).7. The expression of MACC1 has the relationship with tumor size (X2=10.345, P=0.005), depth of invasion(X2=7.879, P=0.004), lymph node metastasis (X2=26.591, P=0.000), vascular invasion (X2=4.481, P=0.037), distant metastasis (X2=6.047, P=0.012), TNM stage (X2=26.591, P=0.000); the expression of SIRT1 has the relationship with tumor size (X2=23.500, P=0.000), depth of invasion (X2=23.730, P=0.000), lymph node metastasis(X2=52.754, P=0.000), vascular invasion (X2 =6.388, P=0.016), distant metastasis (X2=6.434, P=0.013), TNM stage (X2=7.822, P=0.009) related to the clinicopathological parameters; and the expression of MTA3 has the relationship with tumor size (X2=10.139, P=0.003), depth of invasion (X2 =9.028,P=0.000), lymph node metastasis (X2=22.187, P=0.000), vascular invasion (X2=25.291, P=0.000), distant metastasis (X2=13.833, P=0.000), and TNM staging (X2=37.689, P=0.000).8. MACC1, SIRT1 expression positive and MTA3 expression in 42 cases of negative patients, the mean survival time was 66.320 months and the median survival time for 53 months; MACC1, SIRT1 negative and MTA3 positive patients in 10 cases, the mean survival time was 23.972 months and the median survival time for 19 months. The survival time of MACC1, SIRT1 expression positive and MTA3 negative expression was significantly shorter than that of MACC1, SIRT1 negative and MTA3 positive (X2=41.292, P=0.000, P<0.05).9. Univariate survival analysis showed that the EGJA and prognosis in patients with age (X2=4.854, P=0.028), tumor size (X2=5.349, P=0.021), invasive depth (X2=8.579, P=0.003) and vascular invasion (X2=16.085, P=0.000), lymph node metastasis (X2=5.082, P=0.024), distant metastasis (X2=31.174, P=0.000), TNM staging (X2=10.879, P=0.012) significantly (P＜0.05); and and patient gender (X2=0.574, P=0.449), tumor location (X2=0.380, P=0.661), nerve invasion (X2=0.007, P=0.933), morphological type (X2=0.033, P=0.984), pathological grade (X2=6.335, P=0.096) and other factors unrelated (P> 0.05).10. Multivariate survival analysis showed that the EGJA and prognosis in patients with tumor size (X2=5.266, P=0.022), invasive depth (X2=8.446, P=0.004), vascular invasion (X2=15.829, P=0.000), lymph node metastasis (X2=10.424, P=0.015), distant metastasis (X2=30.696, P=0.000),TNM staging (X2=10.720, P=0.013), expression of MACC1(X2=12.860, P=0.002), expression of SIRT1(X2=5.312, P=0.026), expression of (X2=20.695, P=0.000)related (over all X2=42.407, P=0.000, P< 0.05).11. The expression of MACC1 and SIRT1 was positively correlated (r=0.63, P=0.03, P＜0.05). The expression of MACC1 and MTA3 in EGJA showed a negative correlation (r=-0.95, P=0.00, P＜0.05). The expression of SIRT1 and MTA3 in EGJA showed a negative correlation (r=-0.88, P=0.02, P< 0.05). The expression of MACC1, SIRT1, MTA3 with correlation (P<0.05). The expression of MACC1, SIRT1 and MTA3 was related to the expression of the others.Conclusions:1. The prognosis of MACC1, SIRT1 positive expression and MTA3 negative expression is poor, which may be a biological indicator of poor prognosis of EGJA patients.2. MACC1, SIRT1 and MTA3 were correlated with tumor size, invasion depth, vascular invasion, lymph node metastasis and other invasive related clinical pathological factors, MACC1, SIRT1 positive expression and MTA3 negative expression were significantly invasive.3. Tumor size, depth of invasion, vascular invasion, lymph node metastasis, distant metastasis and TNM stage were independent prognostic factors for EGJA patients.4. MACC1, SIRT1 and MTA3 can be used as independent biological indicators for the prognosis of EGJA patients.