The Relationship Between CD147, Connexin43and EGFR Expressions And The Clinical Pathological Features Of Hepatocellular Carcinoma

Objective To detect the expressions of CD147, Connexin43(Cx43) and EGFR in the primary hepatocellular carcinoma (HCC) and explore the relationship between their expressions and the clinicopathological features of HCC. We were devoted to supply theoretical evidence for the gene targeted therapy of HCC.Methods Immunohistochemistry by PV6000detecting system was applied to detect the expressions of CD147, Cx43and EGFR in74HCC tissues,25liver cirrhosis tissues and20normal liver tissues.Results1. The positive expression rates of CD147in HCC tissues, liver cirrhosis tissues and normal liver tissues were63.51%,52.00%and30.00%, respectively. The expressions of CD147between HCC and normal liver tissues showed significant difference (p<0.01). In HCC tissues, CD147was more frequently expressed in the groups with lower differentiation, higher TNM stage (stage Ⅲ-Ⅳ), larger tumor size (>5cm), intravascular cancer embolus (p<0.05), and capsule involvement (p<0.05). CD147appeared more frequently in tumors with infiltrative growth pattern than those with expansive growth pattern (p<0.05). The expression of CD147was not associated with patients’age, gender, liver cirrhosis and cancer embolus in portal vein and alpha fetoprotein(AFP) level in blood before surgery (p>0.05).2. The positive expression rates of Cx43in HCC, cirrhosis liver tissues and normal liver tissues were27.03%,68.00%and95.00%, respectively. The positive expression rate of Cx43in HCC was lower than those in liver cirrhosis tissues and normal liver tissues (p<0.01). In HCC tissues, Cx43was more frequently expressed in the groups with higher differentiation, lower TNM stage (stage Ⅰ-Ⅱ), smaller tumor size (≦5cm), without intravascular cancer embolus (p<0.05), and capsule involvement (p<0.05). Cx43appeared more frequently in tumors with expansive growth pattern than those with infiltrative growth pattern (p<0.05). The expression of Cx43was not associated with patients’age, gender, liver cirrhosis and cancer embolus in portal vein and AFP level in blood before surgery (p>0.05).3. The positive expression rates of EGFR in HCC tissues, liver tissues with cirrhosis and normal liver tissues were66.22%,44.00%and10.00%, respectively. The positive expression rate of EGFR in HCC was higher than those in liver cirrhosis tissues (p<0.05) and normal liver tissues(p<0.01). In HCC tissues, EGFR was more frequently expressed in the groups with lower differentiation, higher TNM stage (stage III-IV), larger tumor size (>5cm), intravascular cancer embolus (p<0.05), and capsule involvement (p<0.05). EGFR appeared more frequently in tumors with infiltrative growth pattern than those with expansive growth pattern (p<0.05). The expression of EGFR was not associated with patients’age, gender, liver cirrhosis and cancer embolus in portal vein and AFP level in blood before surgery (p>0.05).4. In HCC, the expression of Cx43was negative correlated with the expression of CD147(rs’=-0.4082, p=0.0003) and EGFR (rs’=-0.3123, p=0.0068). The expression of CD147was positive correlated with the expression of EGFR (rs’=0.4811, p=0.0000).Conclusions1. CD147was high expressed in HCC tissues, and its expression was associated with poor tumor differentiation, high stage, large tumor size, vascular invasion, capsule involvement, and infiltrative growth pattern. The high expression of CD147in HCC might predicate high malignancy and poor prognosis. The inhibition of CD147expression might be a new candidate for targeted therapy of HCC.2. Cx43was low expressed in HCC, and its expression was associated with tumor differentiation, stage, tumor size, vascular invasion, capsule involvement, and infiltrative growth pattern. The low expressions of Cx43in HCC resulted in the weakened monitoring of tumor cells and depressed function of gap junctional intercellular communication (GJIC), which facilitated the dysfunction of cellular connection and tumor invasion. Increasing the expression of Cx43to revive the function of GJIC might be a new candidate for gene targeted therapy of HCC.3. EGFR was high expressed in HCC tissues, and its expression was related to poor tumor differentiation, high stage, large tumor size, vascular invasion, capsule involvement, and infiltrative growth pattern. The high expression of EGFR in HCC manifests high invasion ability and poor prognosis. The interruption of EGFR expression by targeted inhibitor is a targeted therapy of HCC in clinical trial stage II and III, which could be beneficial to the treat of advanced HCC and prolong the tumor progression-free survival.4. In HCC, CD147and EGFR were high expressed, and Cx43was low expressed. Cx43plays adverse function towards CD147and EGFR in HCC; CD147and EGFR play synergistic action in HCC, which cooperate to regulate the differentiation, progression and invasion of HCC. The detection of Cx43, CD147and EGFR could predicate the progression and invasion of HCC. Cx43, CD147and EGFR might be used as novel and useful markers to predict the prognosis and guide the clinical therapy. Our results provide theory evidences to the gene targeted therapy of HCC.