Linch Mark, Gennatas Spyridon, Kazikin Stanislav, Iqbal Jhangir, Gunapala Ranga, Priest Kathryn, Severn Joanne, Norton Alison, Ayite Bee, Bhosle Jaishree, O'Brien Mary, Popat Sanjay
Royal Marsden Hospital, Fulham Road, SW3 6JJ London, Surrey, UK.
BMC Cancer. 2014 Sep 17;14:674. doi: 10.1186/1471-2407-14-674.
Malignant mesothelioma (MM) carries a poor prognosis and response rates to palliative chemotherapy remain low. Identifying patients with MM that are unlikely to respond to chemotherapy could prevent futile treatments and improve patient quality of life. Studies have suggested that soluble mesothelin is a potential biomarker for early diagnosis and prognosis of MM. We set out to explore the utility of serum mesothelin in routine clinical practice.
We conducted a prospective exploratory study of serum mesothelin levels in 53 consecutive patients with MM at our institution between April 2009 and February 2011. Survival was assessed and analysed by mesothelin level as both continuous and categorical variables using Cox regression models. Differences in response rate between treatment groups were assessed by the Kruskal-Wallis Test.
All 53 patients, who had been given study information agreed to participate. The patients' median age was 69 (range 24-90). Median mesothelin level was 2.7 nM and this value was used to dichotomize categories: ≤2.7 nM (low) and >2.7 nM (high). The progression free survival (PFS) for low vs high mesothelin was 8.0 vs 5.1 months (HR 1.8, p-0.058). When mesothelin was accessed as a continuous variable for PFS the HR was 1.03 (95% CI: 1.01-1.06; p=0.013). The overall survival (OS) for low vs high mesothelin was 17.2 vs 11.3 months (HR 1.9, p=0.088). When mesothelin was assessed as a continuous variable for OS the HR was 1.02 (95% CI: 0.99 - 1.04; p=0.073). Thirty patients received chemotherapy of which 18 had a pre-chemotherapy serum mesothelin level. In these 18 patients, the pre-chemotherapy mesothelin level did not correlate with response.
A single random sample provides information about patient prognosis but does not predict treatment response. We suggest further prospective validation of mesothelin testing as a prognostic biomarker.
恶性间皮瘤（MM）预后较差，姑息化疗的缓解率仍然较低。识别不太可能对化疗产生反应的MM患者可以避免无效治疗并提高患者生活质量。研究表明，可溶性间皮素是MM早期诊断和预后的潜在生物标志物。我们着手探讨血清间皮素在常规临床实践中的效用。
2009年4月至2011年2月期间，我们对本机构连续53例MM患者的血清间皮素水平进行了一项前瞻性探索性研究。使用Cox回归模型，将间皮素水平作为连续变量和分类变量评估并分析生存率。治疗组之间的缓解率差异通过Kruskal-Wallis检验进行评估。
所有53例获得研究信息的患者均同意参与。患者的中位年龄为69岁（范围24-90岁）。间皮素中位水平为２.7 nM，该值用于将类别二分法：≤2.7 nM（低）和>2.7 nM（高）。低间皮素与高间皮素的无进展生存期（PFS）分别为8.0个月和5.1个月（HR 1.8，p=0.058）。当将间皮素作为PFS的连续变量时，HR为1.03（95%CI：1.01-1.06；p=0.013）。低间皮素与高间皮素的总生存期（OS）分别为17.2个月和11.3个月（HR 1.9，p=0.088）。当将间皮素作为OS的连续变量时，HR为1.02（95%CI：0.99-1.04；p=0.073）。30例患者接受了化疗，其中18例患者有化疗前血清间皮素水平。在这18例患者中，化疗前间皮素水平与反应无关。
单次随机样本可提供有关患者预后的信息，但不能预测治疗反应。我们建议进一步对间皮素检测作为预后生物标志物进行前瞻性验证。
