免疫因子表达异常促进宫颈癌微环境免疫失衡

doi:10.3881/j.issn.1000-503X.2016.05.005

Acta Academiae Medicinae Sinica

Acta Academiae Medicinae Sinica ›› 2016, Vol. 38 ›› Issue (5): 522-527.doi: 10.3881/j.issn.1000-503X.2016.05.005

• Orginal Article • Previous Articles Next Articles

Aberrant Expressions of Immune Factors Facilitate the Disequilibrium of Immune Status in Cervical Cancer

Min-yi ZHAO, Juan ZHAO, Ting YANG, Li WANG, Mei-li PEI, Si-juan TIAN, Yang YU, Xiao-feng YANG()

Department of Obstetrics and Gynecology,the First Affiliated Hospital, Xi’an Jiaotong University,Xi’an 710061,China

Received:2016-05-13 Online:2016-10-20 Published:2016-10-10
Supported by:
Supported by the National Natural Sciences Foundation of China (81472428),the Program for New Century Excellent Talents in University (NCET-12-0441),and the Basic Research Foundation of Xi’an Jiaotong University

Abstract

Abstract:

Objective To explore the expressions and co-relationship of immune factors forkhead box p3 (FoxP3),chemokine (C-C motif) ligand 22 (CCL22),tumor necrosis factor receptor superfamily member 40(OX40),and SMAD family member 3 (Smad3) in cervical carcinoma and investigate their immunomodulatory roles in cervical carcinogenesis.Methods Totally 30 cases of cervical carcinoma with adjacent tissues and 20 cases of normal cervix were collected in this study. FoxP3,CCL22,OX40,and Smad3 mRNA expressions were detected by real-time polymerase chain reaction (RT-PCR). Results Compared to normal cervix,the expression levels of FoxP3 and CCL22 mRNA were elevated in neoplastic foci(P=0.000,P=0.002) and tumor periphery (P=0.048,P=0.040).The mRNAs increased modestly in high-grade squamous cell carcinoma focal(P=0.019,P=0.020) and periphery tissue (P=0.023,P=0.031) in comparison with low-grade squamous cell carcinoma. The expression levels of OX40 and Smad3 mRNA were significantly lower in neoplastic foci(P=0.000,P=0.015) than normal cervix. Compared to low-grade squamous cell carcinoma focal and periphery tissue,the mRNAs decreased moderately in high-grade squamous cell carcinoma(P=0.018,P=0.030; P=0.027,P=0.014). In both neoplastic foci and tumor periphery,the mRNA expression level of CCL22 was positively correlated with FoxP3 (r=0.353,P=0.000; r=0.307,P=0.000) but negatively correlated with OX40 (r=-0.288,P=0.031; r=-0.263,P=0.037),while OX40 was positively correlated with Smad3 (r=0.384,P=0.002;r=0.288,P=0.023). The mRNA expressions of FoxP3 and CCL22 were increased in foci and pericarcinous tissues (P=0.024,P=0.039; P=0.032,P=0.034) while Smad3 was decreased in neoplastic foci (P=0.017) in contrast to HPV negative corresponding group. Conclusion FoxP3 and CCL22 expressions increase while OX40 and Smad3 expression decrease at mRNA level in the microenvironment of cervical cancer,which may be associated with such immunological model that the immunosuppressive roles of FoxP3 and CCL22 enhance while the immunity-boosting roles of OX40 and Smad3 are impeded,contributing to the deterioration of immune disequilibrium in local site and cervical cancer carcinogenesis.

Key words: cervical cancer, tumor microenvironment, forkhead box p3, chemokine (C-C motif) ligand 22, tumor necrosis factor receptor superfamily member 4, SMAD family member 3

CLC Number:

Min-yi ZHAO, Juan ZHAO, Ting YANG, Li WANG, Mei-li PEI, Si-juan TIAN, Yang YU, Xiao-feng YANG. Aberrant Expressions of Immune Factors Facilitate the Disequilibrium of Immune Status in Cervical Cancer[J].Acta Academiae Medicinae Sinica, 2016, 38(5): 522-527.

Figures/Tables 4

Fig 1

Fig 2

Fig 3

Table 1

References 19

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基因 Gene	引物序列 Primer sequence	扩增产物长度Product of amplification(bp)
FoxP3	正向 Forward:5’-TTTGCTGATTGTTGCTTTGC-3’ 反向 Reverse:5’-GTTCAACTGATGCTGCCTGA-3’	158
CCL22	正向 Forward:5’-GGTATTTGAACCTGTGGAATTGGAG-3’ 反向 Reverse:5’-CAGGCCCTGGATGACACTGA-3’	163
OX40	正向 Forward:5’-CAAGCCTGGAGTTGACTGTG-3’ 反向 Reverse:5’-GATTGCGTCCGAGCTATTG-3’	139
Smad3	正向 Forward:5’-AGACCTCATGCCCAGCTCTC-3’ 反向 Reverse:5’-GGGGAGGGAGACAGACAAAAC-3’	165
GAPDH	正向 Forward:5’-GCACCGTCAAGGCTGAGAAC-3’ 反向 Reverse:5’-TGGTGAAGACGCCAGTGGA-3’	138

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