[Expression of keratin 1/sialyl-Tn antigen in primary and metastatic cervical squamous cell carcinomas]
- PMID: 41073280
- DOI: 10.3760/cma.j.cn112151-20250530-00378
[Expression of keratin 1/sialyl-Tn antigen in primary and metastatic cervical squamous cell carcinomas]
Abstract
Objective: To investigate the expression of keratin 1 (KRT1) and sialyl-Tn antigen (sTn) in cervical squamous cell carcinoma and its possible mechanism. Methods: Six cervical squamous cell carcinoma specimens were collected at the First Affiliated Hospital of Soochow University, Suzhou, China from 2022 to 2023. Spatial transcriptomics analysis was performed on the paraffin sections of 6 patients to analyze the transcriptomes of invasive squamous cell carcinoma and adjacent normal cervical squamous epithelium. The differential gene KRT1 was selected. Kaplan-Meier survival analysis was used to examine the prognostic value of KRT1 in cervical squamous cell carcinoma patients using the TCGA database. The possible downstream molecule sTn was identified according to literature research. Immunohistochemistry was carried out to investigate the expression of KRT1 and sTn proteins in the primary tumor and metastases of cervical squamous cell carcinoma (40 cases with pelvic lymph node metastasis and 30 cases without). Spearman correlation analysis was conducted to analyze the correlation of their expression. Results: The spatial transcriptomic results of the 6 specimens indicated that the level of KRT1 mRNA significantly decreased in cervical squamous cell carcinoma (compared with that in adjacent normal cervical squamous epithelium), while Kaplan-Meier survival analysis revealed that cervical squamous cell carcinoma patients with low KRT1 mRNA levels (versus high) had a worse prognosis. Immunohistochemistry proved that KRT1 expression was significantly lower in cervical squamous cell carcinoma than in adjacent normal squamous epithelium (P<0.05), but sTn showed the opposite change (increased in carcinoma, P<0.05). The expression changes of KRT1 and sTn were inversely correlated (r=-0.217, P<0.05). In addition, the expression levels of KRT1 and sTn in lymph node metastases were not significantly different from those in primary tumors. Conclusions: The decreased expression of KRT1 in primary cervical squamous cell carcinoma and lymph node metastasis may promote tumor cell proliferation and inhibit apoptosis by upregulating sTn, contributing to the poor prognosis of advanced cervical squamous cell carcinoma.
目的： 探讨角蛋白1（keratin1，KRT1）和唾液酸Tn抗原（sialyl-Tn antigen，sTn）在宫颈鳞状细胞癌中的表达情况，结合文献分析其可能的作用机制。 方法： 收集苏州大学附属第一医院2022—2023年6例宫颈鳞状细胞癌标本，利用空间转录组学，对6例宫颈鳞状细胞癌患者石蜡切片组织中的癌旁正常宫颈鳞状上皮及浸润性鳞状细胞癌进行转录组分析，筛选出差异基因KRT1，利用TCGA数据库，通过Kaplan-Meier生存分析比较KRT1与宫颈鳞状细胞癌预后的关系，通过调研文献明确其可能的下游分子sTn。免疫组织化学法在蛋白水平探究宫颈鳞状细胞癌（40例伴盆腔淋巴结转移，30例无转移）原发灶及转移灶中KRT1及sTn的表达变化，Spearman法对两者的表达变化进行相关性分析。 结果： 6例标本空间转录组结果提示KRT1 mRNA水平在宫颈鳞状细胞癌中显著降低（相较于正常宫颈鳞状上皮），Kaplan-Meier生存分析发现，低KRT1 mRNA水平的宫颈鳞状细胞癌患者具有更差的预后，免疫组织化学法证实KRT1在宫颈鳞状细胞癌中表达显著低于癌旁正常的鳞状上皮，sTn则呈相反变化（癌中升高），差异具有统计学意义（P<0.05），且KRT1和sTn的表达变化呈负相关（r=-0.217，P<0.05）。KRT1和sTn在淋巴结转移灶中的表达水平与原发灶相比，差异无统计学意义。 结论： 晚期宫颈鳞状细胞癌原发灶及淋巴结转移灶中KRT1表达降低、sTn表达升高，可能参与晚期宫颈鳞状细胞癌的不良预后。.