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

• Published in: BMC medicine Vol. 17; no. 1; pp. 106 - 13
• Main Authors: Tian, Meng-Xin, Liu, Wei-Ren, Wang, Han, Zhou, Yu-Fu, Jin, Lei, Jiang, Xi-Fei, Tao, Chen-Yang, Tang, Zheng, Zhou, Pei-Yun, Fang, Yuan, Qu, Wei-Feng, Ding, Zhen-Bin, Peng, Yuan-Fei, Dai, Zhi, Qiu, Shuang-Jian, Zhou, Jian, Lau, Wan Yee, Fan, Jia, Shi, Ying-Hong
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 05.06.2019; BioMed Central; BMC
• Subjects: Adult; Aged; B cells; Biomarkers, Tumor - analysis; Biomarkers, Tumor - metabolism; Cancer; Carcinoma; Carcinoma, Hepatocellular - diagnosis; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - pathology; Cohort Studies; Colorectal cancer; Cytokines; Cytotoxicity; Female; Gene amplification; Genomes; Hepatocellular carcinoma; Hepatology; Homogeneity; Humans; Immune signature; Immunohistochemistry; Immunophenotyping - methods; Liver cancer; Liver Neoplasms - diagnosis; Liver Neoplasms - metabolism; Liver Neoplasms - mortality; Liver Neoplasms - pathology; Lymphocytes; Lymphocytes - pathology; Lymphocytes, Tumor-Infiltrating - metabolism; Lymphocytes, Tumor-Infiltrating - pathology; Male; Medical prognosis; Medical research; Metastasis; Middle Aged; Multivariate analysis; Neoplasm Staging; Novels; Patient outcomes; Patients; Performance assessment; Prognosis; Regression analysis; Regression models; Subgroups; Surgery; Survival; Survival Analysis; Survival prediction; Tissue Array Analysis; Training; Transcriptome; Tumors; Survival prediction; Hepatocellular carcinoma; Prognosis; Immune signature
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/s12916-019-1341-6

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. 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. By using the LASSO method, the TRIS were constructed on the basis of five immune features, CD3 , CD27 , CD68 , CD103 , and PD1 . 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. Our ICPI was a useful and reliable prognostic tool which may offer good individualized prediction capability for HCC patients with early/intermediate stage.