The Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
Masonic Cancer Center, Minneapolis, MN 55455, USA.
Int J Mol Sci. 2022 Nov 1;23(21):13365. doi: 10.3390/ijms232113365.
Ovarian cancer is the most aggressive and lethal of all gynecologic malignancies. The high activity of the MEK/ERK signaling pathway is tightly associated with tumor growth, high recurrence rate, and treatment resistance. Several transcriptional signatures were proposed recently for evaluation of MEK/ERK activity in tumor tissue. In the present study, we validated the performance of a robust multi-cancer MPAS 10-gene signature in various experimental models and publicly available sets of ovarian cancer samples. Expression of four MPAS genes (, , , and ) displayed reproducible responses to MEK/ERK activity modulations across several experimental models and . Levels of , , and expression were also significantly associated with baseline levels of MEK/ERK pathway activity in multiple human ovarian cancer cell lines and ovarian cancer patient samples available from the TCGA database. Initial platinum therapy resistance and advanced age at diagnosis were independently associated with poor overall patient survival. Taken together, our results demonstrate that the performance of transcriptional signatures is significantly affected by tissue specificity and aspects of particular experimental models. We therefore propose that gene expression signatures derived from comprehensive multi-cancer studies should be always validated for each cancer type.
卵巢癌是所有妇科恶性肿瘤中最具侵袭性和致命性的。MEK/ERK 信号通路的高活性与肿瘤生长、高复发率和治疗抵抗密切相关。最近提出了几种转录特征，用于评估肿瘤组织中 MEK/ERK 的活性。在本研究中，我们验证了稳健的多癌种 MPAS 10 基因特征在各种实验模型和公开的卵巢癌样本集中的性能。在几个实验模型中，四个 MPAS 基因（、、、和）的表达对 MEK/ERK 活性的调节表现出可重复的反应。在多个人类卵巢癌细胞系和 TCGA 数据库中可用的卵巢癌患者样本中，和的表达水平也与 MEK/ERK 通路活性的基线水平显著相关。初始铂类治疗耐药和诊断时年龄较大与患者总体生存不良独立相关。总之，我们的结果表明转录特征的性能受到组织特异性和特定实验模型方面的显著影响。因此，我们建议应始终针对每种癌症类型验证来自综合多癌种研究的基因表达特征。
