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联会复合体蛋白2与p16、Ki-67蛋白在子宫颈癌组织中的表达及临床意义
胡会纳, 侯忠臣, 朱远航, 闫金香, 林南山, 肖宁, 李倩, 杨立, 任琛琛
中国实用妇科与产科杂志 ›› 2026, Vol. 42 ›› Issue (3) : 361-365.
PDF(5605 KB)
PDF(5605 KB)
联会复合体蛋白2与p16、Ki-67蛋白在子宫颈癌组织中的表达及临床意义
Expression and clinical significance of synaptonemal complex protein 2， p16， and Ki-67 in cervical cancer tissues
目的 探讨子宫颈癌组织中联会复合体蛋白2（synaptonemal complex protein 2，SYCP2）与p16、Ki-67蛋白的表达，分析其与临床病理特征及预后的关系。方法 选取2018年11月至2021年12月郑州大学第三附属医院病理学明确诊断的124例子宫颈癌患者的病理组织进行SYCP2、p16、Ki-67免疫组织化学法分析。采用生存分析、Cox回归分析法探究三者表达与预后的关系。结果 子宫颈癌患者SYCP2、p16、Ki-67阳性表达率分别为61.3%、76.6%、82.3%，与分化程度、国际妇产科联盟（FIGO）分期、浸润深度、肿瘤最大长径、有无淋巴结转移均有关（P<0.05）。SYCP2与p16、Ki-67三者表达均呈正相关（P<0.05）；SYCP2、p16阳性表达患者的3年生存率低于阴性表达者（P<0.05）；FIGO分期、分化程度、浸润深度、淋巴结转移是影响子宫颈癌预后的独立危险因素。结论 SYCP2与p16、Ki-67在子宫颈癌组织中高表达且呈正相关，SYCP2与p16与子宫颈癌患者不良预后相关。
Objective To investigate the expression of synaptonemal complex protein 2， p16， and Ki-67 in cervical cancer tissues， and analyze their relationships with clinicopathological features and prognosis.Methods A total of 124 cases of pathologically confirmed cervical cancer tissues and 60 cases of paracancerous tissues from the Third Affiliated Hospital of Zhengzhou University between November， 2018 and December， 2021 were selected for immunohistochemical analysis of SYCP2， p16 and Ki-67， with follow-up conducted thereafter.Results The positive expression rates of SYCP2， p16， and Ki-67 in cervical cancer were 61.29%， 76.61%， and 82.26%， respectively， which were correlated with differentiation degree， FIGO stage， invasion depth， maximum tumor diameter， and lymph node metastasis （P<0.05）. Positive correlations were found among SYCP2， p16， and Ki-67 （P<0.05）. The 3-year survival rate of patients with positive SYCP2 or p16 was lower than that of negative patients （P<0.05）.FIGO stage， differentiation degree， invasion depth， and lymph node metastasis were independent prognostic risk factors.Conclusion SYCP2， p16， and Ki-67 are highly expressed in cervical cancer tissues and show a positive correlation with each other； SYCP2 and p16 are associated with poor prognosis in patients with cervical cancer.
cervical cancer / SYCP2 / p16 / Ki-67
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To explore the prognostic value of synaptonemal complex protein-2 (SYCP2) in different subtypes of breast cancer. Patients & materials: In silico bioinformatic analysis was conducted using large databases.SYCP2 was only significantly upregulated in luminal B tumors compared with the adjacent normal tissues. SYCP2 expression was an independent indicator of shorter overall survival in luminal A patients (hazard ratio: 2.269; 95% CI: 1.059-4.862; p = 0.035) and luminal B patients (hazard ratio: 2.546; 95% CI: 1.020-6.355; p = 0.045). Its expression was negatively correlated with the methylation status of multiple CpG sites (cg22214414, cg23241473 and cg07347645) in both luminal A and luminal B tumors.Increased SYCP2 expression might be an independent indicator of shorter overall survival in both luminal A and luminal B patients.
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Unexplained infertility affects 2%-3% of reproductive-aged couples. One approach to identifying genes involved in infertility is to study subjects with this clinical phenotype and a de novo balanced chromosomal aberration (BCA). While BCAs may reduce fertility by production of unbalanced gametes, a chromosomal rearrangement may also disrupt or dysregulate genes important in fertility. One such subject, DGAP230, has severe oligozoospermia and 46,XY,t(20;22)(q13.3;q11.2). We identified exclusive overexpression of SYCP2 from the der(20) allele that is hypothesized to result from enhancer adoption. Modeling the dysregulation in budding yeast resulted in disrupted structural integrity of the synaptonemal complex, a common cause of defective spermatogenesis in mammals. Exome sequencing of infertile males revealed three heterozygous SYCP2 frameshift variants in additional subjects with cryptozoospermia and azoospermia. In sum, this investigation illustrates the power of precision cytogenetics for annotation of the infertile genome, suggests that these mechanisms should be considered as an alternative etiology to that of segregation of unbalanced gametes in infertile men harboring a BCA, and provides evidence of SYCP2-mediated male infertility in humans.Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
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During meiosis, the arrangement of homologous chromosomes is tightly regulated by the synaptonemal complex (SC). Each SC consists of two axial/lateral elements (AEs/LEs), and numerous transverse filaments. SC protein 2 (SYCP2) and SYCP3 are integral components of AEs/LEs in mammals. We find that SYCP2 forms heterodimers with SYCP3 both in vitro and in vivo. An evolutionarily conserved coiled coil domain in SYCP2 is required for binding to SYCP3. We generated a mutant Sycp2 allele in mice that lacks the coiled coil domain. The fertility of homozygous Sycp2 mutant mice is sexually dimorphic; males are sterile because of a block in meiosis, whereas females are subfertile with sharply reduced litter size. Sycp2 mutant spermatocytes exhibit failure in the formation of AEs and chromosomal synapsis. Strikingly, the mutant SYCP2 protein localizes to axial chromosomal cores in both spermatocytes and fetal oocytes, but SYCP3 does not, demonstrating that SYCP2 is a primary determinant of AEs/LEs and, thus, is required for the incorporation of SYCP3 into SCs.
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This study was designed to identify significant differences in gene expression profiles of human papillomavirus (HPV)‐positive and HPV‐negative oropharyngeal squamous cell carcinomas (OPSCC) and to better understand the functional and biological effects of HPV infection in the premalignant pathway. Twenty‐four consecutive patients with locally advanced primary OPSCC were included in a prospective clinical trial. Fresh tissue samples (tumor vs. matched normal epithelium) were subjected to whole transcriptome analysis and the results validated on the same cohort with RT–quantitative real‐time PCR. In a separate retrospective cohort of 27 OPSCC patients, laser capture microdissection of formalin‐fixed, paraffin‐embedded tissue allowed RNA extraction from adjacent regions of normal epithelium, carcinoma in situ (premalignant) and invasive SCC tissue. The majority of patients showed evidence of high‐risk HPV16 positivity (80.4%). Predictable fold changes of RNA expression in HPV‐associated disease included multiple transcripts within the p53 oncogenic pathway (e.g. CDKN2A/CCND1). Other candidate transcripts found to have altered levels of expression in this study have not previously been established (SFRP1, CRCT1, DLG2, SYCP2, and CRNN). Of these, SYCP2 showed the most consistent fold change from baseline in premalignant tissue; aberrant expression of this protein may contribute to genetic instability during HPV‐associated cancer development. If further corroborated, this data may contribute to the development of a non‐invasive screening tool. This study is registered with the UK Clinical Research Network (ref.: 11945).
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Drugs targeting the DNA damage response (DDR) are widely used in cancer therapy, but resistance to these drugs remains a major clinical challenge. Here, we show that SYCP2, a meiotic protein in the synaptonemal complex, is aberrantly and commonly expressed in breast and ovarian cancers and associated with broad resistance to DDR drugs. Mechanistically, SYCP2 enhances the repair of DNA double-strand breaks (DSBs) through transcription-coupled homologous recombination (TC-HR). SYCP2 promotes R-loop formation at DSBs and facilitates RAD51 recruitment independently of BRCA1. SYCP2 loss impairs RAD51 localization, reduces TC-HR, and renders tumors sensitive to PARP and topoisomerase I (TOP1) inhibitors. Furthermore, our studies of two clinical cohorts find that SYCP2 overexpression correlates with breast cancer resistance to antibody-conjugated TOP1 inhibitor and ovarian cancer resistance to platinum treatment. Collectively, our data suggest that SYCP2 confers cancer cell resistance to DNA-damaging agents by stimulating R-loop-mediated DSB repair, offering opportunities to improve DDR therapy.© 2024. The Author(s).
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利益冲突 所有作者均声明不存在利益冲突
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