| Objectives:1. To assay the expression of GOLPH3, mTOR, CXCL12, CXCR4 and CXCR7 in the CRC tissues and noncancerous tissues.2. To analyze correlations between GOLPH3, mTOR, CXCL12, CXCR4 and CXCR7 expression and clinicopathological characteristics in CRC.3. To explore the relationship of GOLPH3, mTOR, CXCL12, CXCR4 and CXCR7 expression with prognosis in CRC. To provide more theoretical basis for the study of prognostic factors and targets of molecular-based therapies.Methods:We performed immunohistochemical analysis for GOLPH3, mTOR, CXCL12,CXCR4 and CXCR7, and evaluated their expression in cancer tissues and noncancerous tissues (negative distant margin) of 90 colorectal cancer specimens ,which had undergone surgical treatment and were not treated with neoadjuvant therapy from January 2009 to December 2010 in the Third Affiliated Hospital of Kunming Medical University. Collected patients’ clinicopathological characteristics, including gender, age, tumor location, tumor diameter, depth of invasion, pathological type, differentiation degree, TNM staging, and analyzed correlations between GOLPH3, mTOR, CXCL12, CXCR4 and CXCR7 expression and clinicopathological characteristics in CRC. We followed up the survival of patients, and explored association between GOLPH3, mTOR, CXCL12, CXCR4 and CXCR7 expression and prognosis in CRC. All statistical calculations were done with the SPSS 19.0 statistical software.Results:1. Expression of GOLPH3, mTOR, C.XCL12, CXCR4 and CXCR7 in colorectal cancer and non-cancerousPositive expression of GOLPH3 was detected in 80% of colorectal cancer tissues(72/90) and 97.8% of non-.cancerous tissues (88/90). Positive expression of mTOR was detected in 96.6% of colorectal cancer tissues (86/9) and 35.6% of non-cancerous tissues (32/90). Positive expression of CXCL12 was detected in 82.2% of colorectal cancer tissues (74/90) and 4.4% of non-cancerous tissues (4/90). Positive expression of of CXCR4 was detected in 68.9% of colorectal cancer tissues (62/90) and 47.8% of non-cancerous tissues (43/90). Positive expression of CXCR7 was detected in 66.7%of colorectal cancer tissues (60/90) and 40% of non-cancerous tissues (36/90).2. Correlations between GOLPH3, mTOR, CXCL12, CXCR4 and CXCR7 expression in CRC tissues.There was a clear positive correlation between GOLPH3 and CXCL12 (r=0.499, P<0.001) , CXCL12 and CXCR4 (r=0.441, P<0.001) , CXCL12 and CXCR7(r=0.473, P=0.01), CXCR4 and CXCR7.(r =0.39, P=0.02) in colorectal cancer,but no significance of the correlation between mTOR and others (P>0.05).3. Correlations between GOLPH3, mTOR, CXCL12, CXCR4 and CXCR7 expression and clinicopathological characteristics in CRC tissuesGOLPH3 expression was closely related to the depth of invasion, lymph node metastasis and age in colorectal cancer (P < 0.05), unrelated other clinical factors (P> 0.05). The positive expression rate of GOLPH3 in serous inside group was significantly higher than that in outside the serosa group (89.5% vs 75%,χ~2 =4.002,P=0.048).mTOR expression was closely related to the pathological type in colorectal cancer (P< 0.001), unrelated other clinical factors (P > 0.05). mTOR was higher expressed in tubular adenocarcinoma than that in mucinous adenocarcinoma group(98.8% vs 50%,χ~2=20.97, P<0.001).CXCL12 expression was significantly correlated with lymph node metastasis in CRC (P=0.01), unrelated other clinical factors (P>0.05). The positive expression rate of CXCL12 in lymph node metastasis group was significantly higher than that without lymph node metastasis group (93.0% vs 72.3%,χ~2=6.572, P=0.01).CXCR4 expression was correlated with tumor site, lymph node metastasis and preoperative CEA level in CRC(P<0.05), unrelated other clinical factors (P>0.05).The positive rate of rectal cancer was significantly higher than that in colon cancer group (χ~2=5.903, P=0.05). The positive rate of lymph node metastasis was significantly higher than that in non-lymph node metastasis group(93.0% vs 46.8%,χ~2=22.37, P=0.013).CXCR7 expression was closely related to TNM stage, pathological type and differentiation degree in CRC(P<0.05), unrelated other clinical factors (P>0.05).The positive expression rate in III and IV staging group was significantly higher than that in I and II staging group (79.6% vs 54.4%, χ~2=6.425, P=0.011). The positive expression rate in tubular adenocarcinoma was significantly higher than that in mucinous adenocarcinoma group( 70.2% vs 16.7% , χ~2 = 5.022, P=0.025).4. Relationship of GOLPH3, mTOR,CXCL12, CXCR4 and CXCR7 expression with prognosis in CRCThe 5-year survival rate of the GOLPH3 positive and negative expression groups was 72.6% and 82.4%. The 5-year survival rate of the mTOR positive and negative expression groups was 73.8% and 16.7%. The 5-year survival rate of the CXCL 12 positive expression group and negative expression group was 77.0% and 35.7%. The 5-year survival rate of CXCR7 positive group and negative expression group was 71.7% and 80.0 %. The 5-year survival rate of CXCR4 positive expression group and negative expression group was 64.5% and 96.4%. However, the Kaplan-Meier survival analysis showed no statistically significant difference (P=0.887). COX regression analysis showed that distant metastasis, pathological type and preoperative intestinal obstruction were the prognostic factors of colorectal cancer (P < 0.05).While gender, age, tumor location, tumor diameter, depth of invasion, differentiation,lymph node metastasis, preoperative CEA level, GOLPH3, mTOR, CXCL12, CXCR4,CXCR7 expression and other factors were not statistically significant (P>0.05).Conclusions:1. The expression of mTOR, CXCL12, CXCR4 and CXCR7 was significantly higher in colorectal cancer tissues than in non-cancerous tissues, and its high expression may be an important factor in the development and progression of colorectal cancer,and they are expected to be new therapeutic targets. The expression of GOLPH3 in cancer tissues was significantly lower than that in non-cancerous tissues, and its relationship with colorectal cancer should to be further studied.2. There was a positive correlation between the expression of GOLPH3 and CXCL12,CXCL12 and CXCR4, CXCR7, CXCR4 and CXCR7 in colorectal cancer, and they were synergistic in the development and progression of colorectal cancer.3. The expression of GOLPH3, CXCL12 and CXCR4 was closely related to lymph node metastasis in colorectal cancer tissues, which is expected to be the biological marker of colorectal cancer metastasis. The expression of mTOR and CXCR7 was related to pathological type .The expression of CXCR4 was correlated with the location of tumor, lymph node metastasis and preoperative CEA. The expression of CXCR7 was closely related to TNM staging and differentiation, which could help to judge the biological behavior of colorectal cancer and provide reference for clinical treatment.4. The expression of GOLPH3, mTOR, CXCL12, CXCR4 and CXCR7 was related to the prognosis of patients with colorectal cancer. The relationship between the GOLPH3, mTOR, CXCL12, CXCR4 and CXCR7 expression with the prognosis of colorectal cancer patients is to be further study. |
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