Mesothelin Expression is Correlated with Chemoresistance in Stage IV Colorectal Cancer
Mesothelin Expression is Correlated with Chemoresistance in Stage IV Colorectal Cancer
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DOI：
10.1245/s10434-021-10507-y
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发表时间：
2021-07-27
影响因子：
3.7
通讯作者：
Ueno, Hideki
中科院分区：
文献类型：
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作者：
Nagata, Ken;Shinto, Eiji;Ueno, Hideki
间皮素（MSLN）是一种存在于间皮细胞上的细胞表面糖蛋白;它在几种上皮性癌症中的表达通常预示着不利的预后。我们研究了MSLN作为替代化学预测生物标志物，并检查了MSLN表达在IV期结直肠癌（CRC）中的影响。方法我们招募了2000年至2019年期间在原发性肿瘤切除术后接受全身化疗的254例CRC患者。对切除标本进行MSLN免疫染色，并根据MSLN表达进行分层。评估了肿瘤MSLN表达与转移灶中肿瘤反应和生存的相关性。结果247例IV期结直肠癌中MSLN高表达41例（16.1%），低表达213例（83.9%）。根据实体瘤疗效评价标准（RECIST）1.1标准，高MSLN表达组和低MSLN表达组的评估者评估的客观缓解率分别为22.0%和45.5%（p = 0.0050）。这两组的疾病控制率分别为65.9%和85.9%（p = 0.00019）。在MSLN高表达的患者中，最初不可切除转移的患者的转化率为0%，而MSLN低表达的患者的转化率为14%（p = 0.0053）。MSLN高表达组的中位总生存期（OS）为1.5年（95%置信区间[CI] 1.1-2.8），而MSLN低表达组的中位总生存期（OS）为2.6年（95%CI 2.2-3.0）。这两组的3年OS率分别为23.5%和41.5%（p = 0.0120）。结论MSLN高表达与IV期大肠癌化疗耐药及预后不良有关。
Background Mesothelin (MSLN) is a cell-surface glycoprotein present on mesothelial cells; its expression in several epithelial cancers generally portends an unfavorable prognosis. We investigated MSLN as a surrogate chemopredictive biomarker and examined the impact of MSLN expression in stage IV colorectal cancer (CRC). Methods We recruited 254 patients with CRC who received systemic chemotherapy following primary tumor resection between 2000 and 2019. Resected specimens were immunostained for MSLN and stratified by MSLN expression. The associations of tumor MSLN expression with tumor response in metastatic lesions and survival were evaluated. Results Of the 247 patients with stage IV CRC, 41 (16.1%) and 213 (83.9%) had high and low MSLN expression, respectively. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, the investigator-assessed objective response rate was 22.0% in the high MSLN expression group and 45.5% in the low MSLN expression group (p = 0.0050). The disease control rates in these groups were 65.9% and 85.9%, respectively (p = 0.00019). In the patients with high MSLN expression, the conversion rate among those with initially unresectable metastases was 0% versus 14% in the patients with low MSLN expression (p = 0.0053). The median overall survival (OS) was 1.5 years (95% confidence interval [CI] 1.1-2.8) in the high MSLN expression group versus 2.6 years (95% CI 2.2-3.0) in the low MSLN expression group. The 3-year OS rates in these groups were 23.5 and 41.5%, respectively (p = 0.0120). Conclusions High MSLN expression is correlated with chemoresistance and poor prognoses in stage IV CRC.