Epidermal growth factor receptor mRNA expression: A potential molecular escape mechanism from regorafenib
Epidermal growth factor receptor mRNA expression: A potential molecular escape mechanism from regorafenib
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表皮生长因子受体 mRNA 表达：瑞戈非尼的潜在分子逃逸机制
DOI：
10.1111/cas.14273
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发表时间：
2020
期刊：
影响因子：
5.7
通讯作者：
Lenz Heinz‐Josef
中科院分区：
文献类型：
--
作者：
Matsusaka Satoshi;Hanna Diana L.;Ning Yan;Yang Dongyun;Cao Shu;Berger Martin D.;Miyamoto Yuji;Suenaga Mitsukuni;Dan Shingo;Mashima Tetsuo;Seimiya Hiroyuki;Zhang Wu;Lenz Heinz‐Josef
瑞戈非尼改善了难治性转移性结直肠癌 (mCRC) 患者的生存率，但遗传性或获得性耐药的机制尚不清楚。共有 50 名难治性转移性结直肠癌患者入组。使用 CellSearch 系统（Veridex LLC，新泽西州，美国）在基线、开始使用瑞格非尼后第 21 天以及疾病进展 (PD) 时进行循环肿瘤细胞 (CTC) 计数。从 CTC 中提取 Poly(A) mRNA，并通过基于 DNA 芯片的多重 PCR 分析上皮和上皮间质转化标记物的基因表达。基线和第 21 天时 CTC 少于 3 个的患者比具有 3 个或更多 CTC 的患者具有更长的无进展生存期（分别为 3.3 个月与 2.0 个月，P = .008 和 3.3 个月与 2.0 个月，P = .004）。基线和第 21 天时 CTC 少于 3 个的患者比具有 3 个或更多 CTC 的患者具有更长的总生存期 (OS)（分别为 10.0 个月与 4.6 个月，P <.001 和 8.7 个月与 3.8 个月，P =.003）。在多变量分析中，CTC 计数在基线和第 21 天仍与 OS 显着相关（P= .019 和 P= .028）。 64% 的患者的循环肿瘤细胞 EGFR 基因表达在第 21 天和/或 PD 时上调。与基线相比，患者在 PD 时的 EGFR 表达显着增加 (P = .041)，并且在第 21 天和/或 PD 时与基线相比 (P = .004)。我们的研究结果表明，CTC 计数和 EGFR 表达可能是瑞格非尼疗效和结果的有用标志。 CTCEGFR表达上调可能是瑞戈非尼治疗下的分子逃逸机制。
Regorafenib has improved the survival of patients with refractory metastatic colorectal cancer (mCRC), yet the mechanisms of inherited or acquired resistance are not well understood. A total of 50 patients with refractory mCRC were enrolled. Circulating tumor cell (CTC) enumeration was carried out at baseline, day 21 after initiation of regorafenib, and at the time of progression of disease (PD) using the CellSearch System (Veridex LLC, NJ, USA). Poly(A) mRNA was extracted from CTCs, and gene expression of epithelial and epithelial‐mesenchymal transition markers was analyzed by a multiplex‐PCR based DNA Chip. Patients with fewer than 3 CTCs at baseline and day 21 had a longer progression‐free survival than those with 3 or more CTCs (3.3 vs 2.0 months,P =.008 and 3.3 vs 2.0 months,P =.004, respectively). Patients with fewer than 3 CTCs at baseline and day 21 had a longer overall survival (OS) than those with 3 or more CTCs (10.0 vs 4.6 months,P <.001 and 8.7 vs 3.8 months,P =.003, respectively). In multivariable analysis, CTC counts remained significantly associated with OS at baseline and day 21 (P= .019 andP= .028). Circulating tumor cellEGFRgene expression was upregulated at day 21 and/or PD in 64% of patients. Patients had significantly increasedEGFRexpression at PD compared to baseline (P =.041) and at day 21 and/or PD compared to baseline (P =.004). Our findings suggest that CTC count andEGFRexpression could be useful markers of regorafenib efficacy and outcomes. Upregulation of CTCEGFRexpression might be a molecular escape mechanism under regorafenib therapy.