Cheng Jianhua, Sun Ruya, Nie Ding, Li Bin, Gui Song Bai, Li Chu Zhong, Zhang Ya Zhuo, Zhao Peng
Department of Cell and Biology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
Department of Biomedical Informatics, Department of Physiology and Pathophysiology, Center for Noncoding RNA Medicine, MOE Key Lab of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University, Beijing, China.
Front Surg. 2022 Jun 21;9:923143. doi: 10.3389/fsurg.2022.923143. eCollection 2022.
Aggressive pituitary adenoma encircling the internal carotid artery has a poor clinical prognosis because of a high surgical risk and a high recurrence rate. This seriously affects patients' quality of life and yet there is no effective medical treatment. The European Diagnostic Guidelines have recommended the use of temozolomide (TMZ) for these aggressive pituitary adenomas, but the treatment remission rate has been less than 50%.
In this study, transcriptome sequencing of pituitary tumour tissues and TMZ-treated pituitary tumour cell lines were employed to explore the significance gene expressions affecting the efficacy of TMZ treatment for pituitary tumours. To clarify the roles of these gene expressions, six adult patients with pituitary adenomas treated in Tiantan Hospital from 2015 to 2020 and a pituitary adenoma cell line (Att20 sensitive to TMZ treatment) were analyzed by mRNA transcriptome sequencing. The differentially expressed genes were assayed by analyzing the sequencing results, and the expression level of these genes was further verified by immunohistochemistry. In addition, Ki67, VEGF, and p53 of the tumour tissues were also verified by immunohistochemistry.
In tumour tissues, mRNA sequencing showed that PTBP1 and EIF5A were significantly overexpressed in primary pituitary adenomas and SLC27A1 was significantly overexpressed in aggressive pituitary adenomas. Also in the pituitary adenoma cell line (AtT20), SLC27A1 expression levels were suppressed by TMZ treatment. Subsequent immunohistochemistry confirmed the sequencing results.
High expression of SLC27A1 and low expression of EIF5A and PTBP1 may be potential indicators to predict the progression of aggressive pituitary adenomas, and patients with high SLC27A1 subtype may be sensitive to TMZ in clinical treatments.
侵袭性垂体腺瘤包绕颈内动脉，由于手术风险高和复发率高，临床预后较差。这严重影响患者的生活质量，且尚无有效的药物治疗方法。欧洲诊断指南推荐使用替莫唑胺（TMZ）治疗这些侵袭性垂体腺瘤，但治疗缓解率低于50%。
在本研究中，采用垂体肿瘤组织和经TMZ处理的垂体肿瘤细胞系的转录组测序，以探索影响TMZ治疗垂体肿瘤疗效的重要基因表达。为阐明这些基因表达的作用，对2015年至2020年在天坛医院接受治疗的6例成年垂体腺瘤患者和一个垂体腺瘤细胞系（对TMZ治疗敏感的Att20）进行mRNA转录组测序分析。通过分析测序结果测定差异表达基因，并通过免疫组织化学进一步验证这些基因的表达水平。此外，还通过免疫组织化学验证肿瘤组织中的Ki67、VEGF和p53。
在肿瘤组织中，mRNA测序显示PTBP1和EIF5A在原发性垂体腺瘤中显著过表达，SLC27A1在侵袭性垂体腺瘤中显著过表达。在垂体腺瘤细胞系（AtT20）中，TMZ处理也抑制了SLC27A1的表达水平。随后的免疫组织化学证实了测序结果。
SLC27A1高表达以及EIF5A和PTBP1低表达可能是预测侵袭性垂体腺瘤进展的潜在指标，SLC27A1高表达亚型的患者在临床治疗中可能对TMZ敏感。
