Circulating kidney injury molecule-1 (KIM-1) and association with outcome to adjuvant immunotherapy in renal cell carcinoma.

Kidney injury molecule-1 (KIM-1) has previously been described as a potential circulating biomarker in RCC.

肾脏损伤分子-1（KIM-1）之前已被描述为RCC中潜在的循环生物标志物。

patients_and_methods

Biomarkers and outcomes among patients who participated in a randomized phase III trial of adjuvant atezolizumab versus placebo in resected RCC (IMmotion010) were evaluated.

在一项随机III期试验中，对接受辅助性阿替利珠单抗与安慰剂治疗的可切除肾细胞癌（RCC）患者进行了生物标志物和结果的评估（IMmotion010）。

This trial did not meet its primary endpoint of disease-free survival (DFS) in the intention-to-treatpopulation.

该试验未达到其主要终点，即意向治疗人群中无病生存（DFS）的改善。

An affinity-based proximity extension proteomics assay was used to compare levels of circulating proteins among baseline (post-nephrectomy) serum samples and samples taken at the time of recurrence.

使用基于亲和力的邻近延伸蛋白质组学测定法比较了基线（肾切除术后）血清样本与复发时样本中循环蛋白的水平。

Results

Serum KIM-1 was the most significantly enriched protein at recurrence versus baseline.

复发时血清中的KIM-1蛋白相比于基线显著富集。

Patients with serum KIM-1high at baseline had worse DFS [hazard ratio(HR) 1.68, 95% confidence interval(CI) 1.35-2.09], but also had improved DFS when treated with adjuvant atezolizumab versus placebo (HR 0.72, 95% CI 0.52-0.99).

基线时血清KIM-1水平高的患者总生存期较差[风险比（HR）1.68，95%置信区间（CI）1.35-2.09]，但接受阿替利珠单抗辅助治疗的患者总生存期较接受安慰剂治疗的患者有所改善（HR 0.72，95% CI 0.52-0.99）。

An increase in KIM-1 during follow-up was associated with worse DFS compared with patients with no increase in KIM-1.

随访期间KIM-1水平升高与没有KIM-1升高的患者相比，总生存期较差。

Within the KIM-1high subgroup, longer DFS following atezolizumab treatment was associated with increased baseline expression of T-effector and Th1 signatures, while shorter DFS was associated with increased baseline expression of matrix remodeling genes and protumor cytokines.

在KIM-1高表达的患者亚组中，接受阿替利珠单抗治疗后的无病生存期（DFS）延长与T效应和Th1信号通路的基线表达增加有关，而DFS缩短则与基质重塑基因和促肿瘤细胞因子的基线表达增加有关。

Conclusions

These analyses suggest that elevated post-nephrectomy plasma KIM-1 level and kinetics are prognostic, supporting the hypothesis that KIM-1 is a biomarker for minimal residual disease in RCC.

这些分析表明，肾切除术后血浆KIM-1水平及其动态变化具有预后意义，支持KIM-1是肾细胞癌（RCC）微小残留病的生物标志物的假设。

As KIM-1high patients are also enriched for benefit from adjuvant immunotherapy, biomarker-driven adjuvant therapy should be evaluated as a potential new paradigm in RCC.

鉴于KIM-1高表达的患者也从辅助免疫治疗中获益，应评估基于生物标志物的辅助治疗作为肾细胞癌（RCC）中潜在的新治疗范式。