论文标题：Tissue-infiltrating lymphocytes signature predicts survival in patients with early/intermediate stage hepatocellular carcinoma

期刊：BMC Medicine

作者：Meng-Xin Tian†, Wei-Ren Liu†, Han Wang†, Yu-Fu Zhou†, Lei Jin, Xi-Fei Jiang, Chen-Yang Tao, Zheng Tang, Pei-Yun Zhou, Yuan Fang, Wei-Feng Qu, Zhen-Bin Ding, Yuan-Fei Peng, Zhi Dai, Shuang-Jian Qiu, Jian Zhou, Wan Yee Lau, Jia Fan and Ying-Hong Shi

发表时间：2019/06/05

数字识别码：10.1186/s12916-019-1341-6

原文链接：http://t.cn/AiN7A0WY

微信链接：https://mp.weixin.qq.com/s/QX1J52gSYO2Aa9Hz-ogaTw

肝细胞肝癌（简称肝癌）是一种常见的恶性肿瘤，全球范围内年死亡患者超过约70000例。其临床预后不仅与肿瘤自身和潜在肝脏疾病有关，同时与肿瘤异质性也密切相关。目前，针对肝癌患者的预后评估，依赖于肿瘤个数、直径、血管侵犯和淋巴结转移等传统指标。研究指出，肝癌是一种异质性极高的肿瘤。处于同一肿瘤分期的肝癌患者，其临床预后可能不尽相同。因此，如何从肿瘤微环境探寻新颖的预测指标，将有助于为肝癌患者制定个体化的术后管理方案，促进患者远期生存。

© vshivkova / Getty Images / iStock

近日，复旦大学附属中山医院肝癌研究所史颖弘教授团队在BMC Medicine 发表了文章"Tissue-Infiltrating Lymphocytes Signature Predicts Survival in Patients with Early/Intermediate Stage Hepatocellular Carcinoma”。作者通过免疫组织化学技术在352例肝癌组织样本（训练集）内检测了28种肝癌免疫特征。根据LASSO Cox筛选出5种免疫特征，建立了新型的组织相关免疫特征（tissue-related immune signature，TRIS）评分，包括CD3intratumoral (T) , CD27T , CD68peritumoral (P) , CD103T和PD1T等。

单因素和多因素分析表明，TRIS评分、GGT、肿瘤直径和肿瘤分化是早/中期肝癌患者独立的预后因素。据此，作者联合以上四种指标构建出肝癌患者个体化的免疫临床预后指数模型（immune clinical prognostic index，ICPI）。

为进一步验证模型的可靠性，作者利用在393例独立的肝癌队列中（验证集）检测TRIS评分。训练集和验证集的C-index分别为0.691（95%CI, 0.642-0.739）和0.686（95%CI, 0.637-0.735）。ROC曲线分析显示，在训练集和验证集内ICPI模型的预测能力均优于Okuda、CLIP、LCSGJ和BCLC等7种传统肝癌分期系统。作者根据58.5和86.2作为cutoff值，将队列分为3个亚组（Score 1、Score 2和Score 3）。同质性检验和校正AIC统计分析证明，各亚组的同质性和AIC好于其他7种肝癌分期。同样，该结果在训练集中得到进一步验证。因此，肝癌TRIS评分可能补充了传统临床病理指标在预后预测方面的不足。与传统肝癌分期系统相比，ICPI模型在早/中期肝癌患者中可能提供更好的预后预测效果。

摘要：

Background

Intratumoral immune infiltrates have manifested a robust prognostic signature in patients with hepatocellular carcinoma (HCC). We hypothesized that a novel tissue-related immune signature (TRIS) could improve the prediction of postoperative survival for patients diagnosed with early/intermediate HCC.

Methods

Twenty-eight immune features were immunohistochemically examined on 352 HCC specimens. The LASSO Cox regression model was used to construct a five-feature-based TRIS. The univariate and multivariate Cox analyses were performed. Based on independent predictors, the immune-clinical prognostic index (ICPI) was established. Performance assessment was measured with C-index and compared with seven traditional staging systems. The independent validation cohort (n = 393) was included to validate the model.

Results

By using the LASSO method, the TRIS were constructed on the basis of five immune features, CD3intratumoral (T), CD27T, CD68peritumoral (P), CD103T, and PD1T. Multivariate Cox analysis showed that the TRIS was an independent prognostic predictor. In the training cohort, γ-glutamyl transferase, tumor diameter, tumor differentiation, and TRIS were incorporated into the ICPI. The ICPI presented satisfactory discrimination ability, with C-index values of 0.691 and 0.686 in the training and validation cohorts, respectively. Compared with seven conventional staging systems (C-index, training cohort, 0.548–0.597; validation cohort, 0.519–0.610), the ICPI exhibited better performance for early/intermediate-stage HCCs. Further, the patients were categorized into three subgroups with X-tile software, and the stratified ICPI presented a superior corrected Akaike information criterion and homogeneity in both cohorts.

Conclusions

Our ICPI was a useful and reliable prognostic tool which may offer good individualized prediction capability for HCC patients with early/intermediate stage.

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期刊介绍:

BMC Medicine(https://bmcmedicine.biomedcentral.com/,9.088 - 2-year Impact Factor, 9.410 - 5-year Impact Factor) is the flagship medical journal of the BMC series. An open access, open peer-reviewed general medical journal, BMC Medicinepublishes outstanding and influential research in all areas of clinical practice, translational medicine, medical and health advances, public health, global health, policy, and general topics of interest to the biomedical and sociomedical professional communities. We also publish stimulating debates and reviews as well as unique forum articles and concise tutorials.

（来源：科学网）