| Cervical cancer is the second largest female malignancy in the world and the largest female malignancy in developing countries.In recent years,the incidence of cervical squamous cell carcinoma and adenocarcinoma has increased considerably in women younger than 35 years.Therefore,it is very important to diagnose early cervical cancer.Persistent infection of high-risk human papillomavirus(HR-HPV)is a recognized cause of cervical cancer,which is preventable and treatable.In the clinic,although a large number of HPV nucleic acid detection and Thin Prep cell test has been used for early screening of cervical lesions,but also brought high false-positive,low sensitivity and different TCT reports from pathologists.Alpha actinin 4(ACTN4)is a kind of protein with actin cross-linking,belonging to the superfamily of spectrin,the gene is located on 19q13.It has found that ACTN4 is closely related to the occurrence of malignant tumors,such as gastric cancer,esophageal cancer,colorectal cancer,breast cancer,cell movement and postoperative metastasis.Objective: To investigate the effect of ACTN4 in women with different cervical lesions,expressed in m RNA,protein expression and protein of peripheral blood,and to evaluate the value of ACTN4 as a marker for cervical lesions.Methods: 1.20 cases of control cervical tissues(cervical cancer and CIN removed),10 cases of LSIL(CIN I)tissues,5 cases of HSIL(CIN?,CIN?)tissues and 30 cases of cervical cancer tissues were collected.q RT-PCR technology was used to detect the expression of ACTN4 m RNA.2.Different sections of cervical tissue paraffin were collected.Among them,there were 20 cases of control cervical tissues(cervical cancer and CIN removed),10 cases of LSIL(CIN I)tissues,12 cases of HSIL(CIN?,CIN?)tissues and 31 cases of cervical cancer tissues.Using immunohistochemical staining,two deputy chief physicians were invited to read and score the sections,assess the expression of ACTN4 and the location of the expression in cervical cell,and investigate the relationship between the level of ACTN4 protein and cervical lesions.3.Peripheral bloods from 20 cases of control person(cervical cancer and CIN removed),8 cases of LSIL(CIN I),32 cases of HSIL(CIN?,CIN?),13 cases of cervical cancer were collected.ELISA was used to detect peripheral blood concentration of ACTN4 protein from different cervical lesions.Screening value of ?CINIII using ACTN4 protein concentration in peripheral blood can be explored.Results: 1.ACTN4 m RNA is expressed in 100%(32/32)?CINIII cervical tissues,72.7%(24/33)in <CINIII cervial tissues;Relative experience(RQ)of ACTN4 m RNA in?CINIII cervical tissues was 0.1111±0.1164,RQ of ACTN4 in <CINIII(+)cervical tissues was 0.0261±0.0219,the difference was statistically significant(t=-3.49,P<0.05);RQ of ACTN4 in FIGO I cervical cancer tissue was 0.0329±0.0253,RQ of ACTN4 in FIGO II+ cervical cancer tissue was 0.1453±0.1329,the difference was statistically significant(t=-3.137,P<0.05);RQ of ACTN4 in cervical cancer without lymph node metastasis was 0.0507±0.0332,RQ of ACTN4 in cervical cancer tissues with lymph node metastasis was 0.1509 ± 0.1138,the difference was statistically significant(t=-2.504,P=0.025).2.The score of ACTN4 protein in control cervical tissues was 1.13±1.154,in LSIL(CIN 1)tissues was 1.15±1.104,in HSIL(CIN II,CIN III)tissues was 2.82±0.874,in cervical cancer was 3.77±0.805.The score of <CINIII cervical tissue was 1.34±1.22,and the score of ?CINIII cervical tissue group was 3.61±0.92;<CINIII group compared with the ?CINIII group,the two groups were statistically significant(t=8.17,P<0.05).The expression of ACTN4 protein in ?CINIII group was higher than <CINIII group.The ACTN4 score of well differentiated cervical cancer was 2.83±0.408,and the score in middle and poor differentiated cervical cancer was 4±0.722.The difference between the two groups was statistically significant(t=-5.243,P<0.001).The expression of ACTN4 mainly depends on cytoplasm.3.The concentration of ACTN4 protein(<CINIII)was 28.5078±11.2977,and the concentration of ACTN4(?CINIII)was 43.744±23.6377,unit(pg/m L).The area under ROC curve of SCC in diagnosing ?CINIII cervical lesions was 0.838,detected alone,when cutoff?1?g/L,sensitivity and specificity were 68.6% and 92.1%;the area under ROC curve of ACTN4 in diagnosing ?CINIII cervical lesions was 0.721 detected alone,when cutoff ?33.07 pg/m L,sensitivity and specificity were 68.6% and76.3%.The area of ROC curve in diagnosing ?CINIII cervical lesions was 0.879,combined detection of ACTN4 and SCC.The difference was statistically significant(t=-3.466,P=0.001).The combined detection of ACTN4 and SCC in ?CINIII cervical lesions is superior to SCC alone and ACTN4 alone.ACTN4 is superior to SCC in the screening of cervical adenocarcinoma.Conclusion:1.ACTN4 mRNA is highly expressed in ? CINIII cervical lesions,ACTN4 m RNA expression in patients with FIGO?cervical cancer was lower than patients with FIGO II+ stage,ACTN4 m RNA expression with lymph node metastasis was higher than that in patients without lymph node metastasis.2.ACTN4 protein in ?CINIII cervical lesions is higher than <CINIII group,ACTN4 is mainly expressed in the cytoplasm of cervical cells,the expression of ACTN4 protein in poorly differentiated cervical cancer was higher than that in patients with high cervical cancer.3.ACTN4 protein in peripheral blood of patients with ? CINIII patients was higher than <CINIII group.The area under the ROC curve for the diagnosis of ?CINIII patients by ACTN4 alone was 0.721,and the area under the ROC curve for diagnosing ?CINIII patients was 0.879 by the combined detection of SCC and ACTN4.The cutoff point(sensitivity =68.6%,specificity =76.3%)of ?CINIII cervical lesions can be detected using 33.07 pg/ml as ACTN4 concentration in peripheral blood.ACTN4 is superior to SCC in early diagnosis of cervical adenocarcinoma. |
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