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Histopathology-based immunoscore predicts recurrence for intrahepatic cholangiocarcinoma after hepatectomy

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Abstract

Intrahepatic cholangiocarcinoma (ICC) is a rare malignancy with poor prognosis. The evaluation of recurrence risk after liver resection is of great importance for ICCs. We aimed to assess the prognostic value of intra- and peritumoral immune infiltrations and to establish a novel histopathology-related immunoscore (HRI) associated with ICC recurrence. A total of 280 ICC patients who received curative resection between February 2005 and July 2011 were enrolled in our study. Patients were randomly assigned to the derivation cohort (n = 176) or the validation cohort (n = 104). Sixteen immune biomarkers in both intra- and peritumoral tissues were examined by immunohistochemistry. The least absolute shrinkage and selection operator (LASSO) Cox model was used to establish the HRI score. Cox regression analysis was used for multivariate analysis. Nine recurrence-related immune features were identified and integrated into the HRI score. The HRI score was used to categorize patients into low-risk and high-risk groups using the X-tile software. Kaplan–Meier analysis presented that the HRI score showed good stratification between low-risk and high-risk groups in both the derivation cohort (P < 0.001) and the validation cohort (P = 0.014), respectively. Multivariate analysis demonstrated that serum γ-glutamyl transpeptidase, carbohydrate antigen 19-9, lymphoid metastasis, tumor numbers, and the HRI score were independent risk factors associated with recurrence-free survival (RFS). The combination of Shen’s model and HRI score provided better performance in recurrence prediction compared with traditional staging systems. The HRI score might serve as a promising RFS predictor for ICC with prognostic values.

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Abbreviations

AJCC:

American Joint Committee on Cancer

ALT:

Alanine aminotransferase

AUC:

Area under curve

CA19-9:

Carbohydrate antigen 19-9

CEA:

Carcino-embryonic antigen

GGT:

γ-Glutamyl transpeptidase

HRI:

Histopathology-related immunoscore

ICC:

Intrahepatic cholangiocarcinoma

LASSO:

Least absolute shrinkage and selection operator

LCSGJ:

Liver Cancer Study Group of Japan

PD1:

Programmed cell death 1

PD-L1:

Programmed death ligand-1

RFS:

Recurrence-free survival

ROC:

Receiver operating characteristic curve

TAM:

Tumor-associated macrophage

TMA:

Tissue microarray

Tregs:

Regulatory T cells

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Funding

This work was supported by grants from the National Natural Science Foundation of China (Nos. 81472674, 81502486, 81773067 and 81800790), the National Key Sci-Tech Project (2012ZX10002011-002), and a China Postdoctoral Science Foundation funded project (2018M640343). The work was sponsored by the Shanghai Sailing Program (19YF1407800), and the Shanghai Committee of Science and Technology, China (No. 16JC1404000).

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  1. Meng-Xin Tian, Yu-Fu Zhou and Wei-Feng Qu contributed equally to this work.

Authors and Affiliations

  1. Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China

    Meng-Xin Tian, Yu-Fu Zhou, Wei-Feng Qu, Wei-Ren Liu, Lei Jin, Xi-Fei Jiang, Han Wang, Chen-Yang Tao, Pei-Yun Zhou, Yuan Fang, Zhen-Bin Ding, Yuan-Fei Peng, Jian Zhou, Jia Fan & Ying-Hong Shi

  2. Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China

    Meng-Xin Tian, Yu-Fu Zhou, Wei-Feng Qu, Wei-Ren Liu, Lei Jin, Xi-Fei Jiang, Han Wang, Chen-Yang Tao, Pei-Yun Zhou, Yuan Fang, Zhen-Bin Ding, Yuan-Fei Peng, Jian Zhou, Jia Fan & Ying-Hong Shi

  3. Institutes of Biomedical Sciences, Fudan University, Shanghai, China

    Jian Zhou & Jia Fan

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  1. Meng-Xin Tian
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Contributions

MXT, YFZ, WFQ, JF, and YHS performed and analyzed the experiments. WRL, LJ, XFJ, HW, CYT, PYZ, YF, ZBD, and YFP collected the clinical data. MXT, YFZ, WFQ, JZ, JF, and YHS designed the clinical trial protocol and experiments. All the authors approved the final version of the manuscript.

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Correspondence to Ying-Hong Shi.

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The authors declare that they have no conflict of interest.

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The study was approved by the institutional review board of Zhongshan Hospital on 31/1/2018 and was conducted in accordance with the standards of the Declaration of Helsinki.

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Written informed consents for the use of their specimens and anonymous clinical data were obtained from all individual participants in the study prior to hepatectomy.

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Tian, MX., Zhou, YF., Qu, WF. et al. Histopathology-based immunoscore predicts recurrence for intrahepatic cholangiocarcinoma after hepatectomy. Cancer Immunol Immunother 68, 1369–1378 (2019). https://doi.org/10.1007/s00262-019-02371-3

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