Background

Identification of specific risk groups for recurrence after surgery for isolated colorectal liver metastases (CRLM) remains challenging due to the heterogeneity of the disease. Classical clinicopathologic parameters have limited prognostic value. The aim of this study was to identify a gene expression signature measured in CRLM discriminating early from late recurrence after partial hepatectomy.

Methods

CRLM from two patient groups were collected: I) with recurrent disease ≤12 months after surgery (N = 33), and II) without recurrences and disease free for ≥36 months (N = 30). The patients were clinically homogeneous; all had a low clinical risk score (0–2) and did not receive (neo-) adjuvant chemotherapy. Total RNA was hybridised to Illumina arrays, and processed for analysis. A leave-one-out cross validation (LOOCV) analysis was performed to identify a prognostic gene expression signature.

Results

LOOCV yielded an 11-gene profile with prognostic value in relation to recurrent disease ≤12 months after partial hepatectomy. This signature had a sensitivity of 81.8%, with a specificity of 66.7% for predicting recurrences (≤12 months) versus no recurrences for at least 36 months after surgery (X² P < 0.0001).

Conclusion

The current study yielded an 11-gene signature at mRNA level in CRLM discriminating early from late or no relapse after partial hepatectomy.

中文翻译：

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大肠肝转移的mRNA表达谱作为部分肝切除术后早期复发的新型生物标志物。

背景

由于疾病的异质性，对于孤立的结直肠肝转移（CRLM）手术后复发的特定危险人群的鉴定仍然具有挑战性。经典的临床病理参数具有有限的预后价值。这项研究的目的是鉴定在CRLM中测量的基因表达特征，以区别于部分肝切除术后的早期复发与晚期复发。

方法

收集了两个患者组的CRLM：I）术后≤12个月的复发性疾病（N = 33），II）≥36个月无复发且无疾病的患者（N = 30）。患者临床上均一。所有患者的临床风险评分均较低（0–2），并且未接受（新）辅助化疗。将总RNA与Illumina阵列杂交，并进行分析。进行留一法交叉验证（LOOCV）分析以鉴定预后基因表达特征。

结果

LOOCV产生的11个基因谱具有与部分肝切除术后≤12个月的复发性疾病有关的预后价值。该签名的敏感性为81.8％，特异性为66.7％，可预测复发（≤12个月），而术后至少36个月无复发（X ² P <0.0001）。

结论

目前的研究在CRLM的mRNA水平上产生了11个基因的信号，可以区分早期或部分肝切除术后无复发。