The Expression And Down-regulation Mechanism Of CYFIP1in Nasopharyngeal Carcinoma

Objective Nasopharyngeal carcinoma (NPC) is one of the most frequentmalignant diseases in guangdong, guangxi, hunan and fujian of China and othersouth-east Asians. Therefore, it is of great interest and importance to findvaluable biomarkers for early diagnosis for this malignancy. The origin anddevelopment of NPC is a multigene process, involving a variety of the activationof oncogene and tumor suppressor gene inactivation and lots of changes in cellbiology behavior. In recent years, tumor suppressor genes have been consideredas a more important factor in the development of NPC. The newest study foundthat CYFIP1play an important role in variable cancers. The present study aimsat discussing the expression level and down-regulation mechanism of CYFIP1inNPC.Method1. qRT-PCR was applied to detect the CYFIP1expression level inboth NPC and normal nasopharyngeal tissues and clinical pathologyrelationship.2. MS-PCR was applied to analyze the methylation status in bothNPC and normal nasopharyngeal tissues. And the relationship betweenmethylation status and CYFIP1expression level was also discussed.3.Denatured polyacrylamide gel electrophoresis was applied to measure the LOHstatus of CYFIP1. Result1. The mRNA relative expression level of CYFIP1in63NPC cases is5.26±2.43and in42normal nasopharyngeal cases is3.15±1.68. The differenceis statistically significant(P<0.05). Based on clinical pathology data, both theexpression level of T1~T2is statistically higher than T3~T4and in NPC(P<0.05). What is more, the expression level of both lymph node metastasis anddistant metastasis groups are higher than those who have no lymph nodemetastasis and distant metastasis(P<0.05). The difference is not statisticallysignificant between CYFIP1mRNA expression level and age, gender,histological type.2.29of63NPC cases (46.1%) was methylated in CYFIP1promoter region. And none of42normal nasopharyngeal cases (0%) wasmethylated. The difference is statistically significant in the degree of methylationstatus between NPC cases and normal nasopharyngeal cases (P<0.05).Furthermore, the difference is not statistically significant between CYFIP1methylation degree and age, gender, clinical stage or histological type (P>0.05).3.23of63NPC cases (36.5%) was in LOH status of CYFIP1promoter region.And only1of42normal nasopharyngeal cases (2.4%) was in LOH status. Thedifference is statistically significant in the degree of LOH status between NPCcases and normal nasopharyngeal cases (P<0.05). Furthermore, the difference isnot statistically significant between CYFIP1LOH degree and age, gender,clinical stage or histological type (P>0.05).4. CYFIP1mRNA expression level was inverse correlated its methylation degree (rs=-0.681, P<0.01) and its LOHdegree (rs=-0.445, P<0.05)Conclusion1. The reduced expression level of CYFIP1was detected and it was associatedwith invasive range, lymph node metastasis and distant metastasis, whichsuggested that decreased expression of CYFIP1may play a key role in NPCdevelopment.2. The increased methylation degree of CYFIP1was detected andit was inverse correlated with CYFIP1expression, which suggested thatincreased methylation degree of CYFIP1is one of decreased CYFIP1expression.3. The increased LOH degree of CYFIP1was detected and it was inversecorrelated with CYFIP1expression, which suggested that increased LOH degreeof CYFIP1is one of the important genetic factors in NPC development.