Fornaro Lorenzo, Vivaldi Caterina, Lin Dong, Xue Hui, Falcone Alfredo, Wang Yuzhuo, Crea Francesco, Bootman Martin D
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Experimental Therapeutics, BC Cancer Research Centre, Vancouver, British Columbia, Canada.
PLoS One. 2017 Aug 28;12(8):e0182818. doi: 10.1371/journal.pone.0182818. eCollection 2017.
T-type calcium channels (TTCCs) mediate calcium influx across the cell membrane. TTCCs regulate numerous physiological processes including cardiac pacemaking and neuronal activity. In addition, they have been implicated in the proliferation, migration and differentiation of tumour tissues. Although the signalling events downstream of TTCC-mediated calcium influx are not fully elucidated, it is clear that variations in the expression of TTCCs promote tumour formation and hinder response to treatment.
We examined the expression of TTCC genes (all three subtypes; CACNA-1G, CACNA-1H and CACNA-1I) and their prognostic value in three major solid tumours (i.e. gastric, lung and ovarian cancers) via a publicly accessible database.
In gastric cancer, expression of all the CACNA genes was associated with overall survival (OS) among stage I-IV patients (all p<0.05). By combining the three potential biomarkers, a TTCC signature was developed, which retained a significant association with OS both in stage IV and stage I-III patients. In lung and ovarian cancer, association with OS was also significant when all tumour stages were considered, but was partly lost or inconclusive after splitting cases into localized and metastatic subsets.
Alterations in CACNA gene expression are linked to tumour prognosis. Gastric cancer represents the most promising setting for further evaluation.
T型钙通道(TTCCs)介导钙离子跨细胞膜内流。TTCCs调节众多生理过程,包括心脏起搏和神经元活动。此外,它们还与肿瘤组织的增殖、迁移和分化有关。尽管TTCC介导的钙离子内流下游的信号事件尚未完全阐明,但很明显,TTCCs表达的变化促进肿瘤形成并阻碍治疗反应。
我们通过一个公开可用的数据库,研究了TTCC基因(所有三种亚型;CACNA-1G、CACNA-1H和CACNA-1I)在三种主要实体瘤(即胃癌、肺癌和卵巢癌)中的表达及其预后价值。
在胃癌中,所有CACNA基因的表达与I-IV期患者的总生存期(OS)相关(所有p<0.05)。通过组合这三种潜在生物标志物,构建了一个TTCC特征,其在IV期和I-III期患者中均与OS保持显著相关性。在肺癌和卵巢癌中,当考虑所有肿瘤分期时,与OS的相关性也很显著,但在将病例分为局限性和转移性亚组后,部分相关性丧失或不明确。
CACNA基因表达的改变与肿瘤预后相关。胃癌是进一步评估最有前景的研究对象。