Lou Yuming, Jin Shuxun, Hong Xing, Hong Zhongwu, Xu Chaoyang
Department of Breast and Thyroid Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China.
Department of Breast and Thyroid Surgery, Shaoxing People's Hospital, Shaoxing, China.
Transl Cancer Res. 2023 Jan 30;12(1):150-162. doi: 10.21037/tcr-22-2890. Epub 2023 Jan 13.
At present, due to the heterogeneity of breast cancer, common tumor markers have certain limitations in clinical prognostic evaluation. This suggests an unmet need for markers to predict clinical outcomes and potentially guide targeted therapies. The present study sought to explore the expression level and clinical significance of undifferentiated embryonic cell transcription factor 1 (UTF1) in breast cancer.
Immunohistochemistry (IHC) was used to detect the expression of UTF1 in 221 breast cancer samples. The clinical significance of UTF1 protein expression in breast cancer tissues was evaluated by combining clinicopathological parameters and UTF1 expression profile. We performed 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays to evaluate the effect of UTF1 on Bcap37 cell proliferation. Wound healing assay and transwell migration assay were used to evaluate the changes of cell invasion and migration ability, respectively. All experiments were performed with 3 biological replicates. Genomic differences after UTF1 overexpression were evaluated by RNA sequencing technology and the possible functions and regulatory mechanisms were elucidated.
The findings showed that UTF1 expression level was significantly correlated with tumor size (P=0.004), but not with patient age, tumor histological stage, lymph node metastasis, as well as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), and Ki67 expression levels. Kaplan-Meier survival analysis and Cox proportional hazard model indicated that UTF1 expression was significantly associated with overall survival (OS) time of breast cancer patients. The median survival time of patients with high expression level of UTF1 was shorter compared with that of patients with low UTF1 expression level. The results of cell experiments showed that UTF1 overexpression could significantly promote the growth, proliferation, migration, and invasion of breast cancer cells. The RNA sequencing results showed that UTF1 was not only closely related to apoptosis genes, but also closely related to the nuclear factor (NF)-kappa B pathway.
The findings of the current study indicate that UTF1 is involved in occurrence and tumor progression and is significantly associated with prognosis of breast cancer patients.
目前，由于乳腺癌的异质性，常见肿瘤标志物在临床预后评估中存在一定局限性。这表明预测临床结果并潜在指导靶向治疗的标志物存在未满足的需求。本研究旨在探讨未分化胚胎细胞转录因子1（UTF1）在乳腺癌中的表达水平及临床意义。
采用免疫组织化学（IHC）检测221例乳腺癌样本中UTF1的表达。通过结合临床病理参数和UTF1表达谱评估UTF1蛋白表达在乳腺癌组织中的临床意义。我们进行了3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐（MTT）和克隆形成试验，以评估UTF1对Bcap37细胞增殖的影响。分别采用伤口愈合试验和Transwell迁移试验评估细胞侵袭和迁移能力的变化。所有实验均进行3次生物学重复。通过RNA测序技术评估UTF1过表达后的基因组差异，并阐明其可能的功能和调控机制。
研究结果表明，UTF1表达水平与肿瘤大小显著相关（P=0.004），但与患者年龄、肿瘤组织学分期、淋巴结转移以及雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2（HER-2）和Ki67表达水平无关。Kaplan-Meier生存分析和Cox比例风险模型表明，UTF1表达与乳腺癌患者的总生存（OS）时间显著相关。UTF1高表达患者的中位生存时间低于UTF1低表达患者。细胞实验结果表明，UTF1过表达可显著促进乳腺癌细胞的生长、增殖、迁移和侵袭。RNA测序结果表明，UTF1不仅与凋亡基因密切相关，还与核因子（NF）-κB通路密切相关。
本研究结果表明，UTF1参与乳腺癌的发生和肿瘤进展，并与乳腺癌患者的预后显著相关。
