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Tissue-infiltrating lymphocytes signature predicts survival in patients with early/intermediate stage hepatocellular carcinoma
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/inte...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549297/ https://www.ncbi.nlm.nih.gov/pubmed/31164128 http://dx.doi.org/10.1186/s12916-019-1341-6 |
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author | 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 |
author_facet | 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 |
author_sort | Tian, Meng-Xin |
collection | PubMed |
description | 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, CD3(intratumoral (T)), CD27(T), CD68(peritumoral (P)), CD103(T), and PD1(T). 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12916-019-1341-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6549297 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-65492972019-06-06 Tissue-infiltrating lymphocytes signature predicts survival in patients with early/intermediate stage hepatocellular carcinoma 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 BMC Med Research Article 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, CD3(intratumoral (T)), CD27(T), CD68(peritumoral (P)), CD103(T), and PD1(T). 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12916-019-1341-6) contains supplementary material, which is available to authorized users. BioMed Central 2019-06-05 /pmc/articles/PMC6549297/ /pubmed/31164128 http://dx.doi.org/10.1186/s12916-019-1341-6 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article 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 Tissue-infiltrating lymphocytes signature predicts survival in patients with early/intermediate stage hepatocellular carcinoma |
title | Tissue-infiltrating lymphocytes signature predicts survival in patients with early/intermediate stage hepatocellular carcinoma |
title_full | Tissue-infiltrating lymphocytes signature predicts survival in patients with early/intermediate stage hepatocellular carcinoma |
title_fullStr | Tissue-infiltrating lymphocytes signature predicts survival in patients with early/intermediate stage hepatocellular carcinoma |
title_full_unstemmed | Tissue-infiltrating lymphocytes signature predicts survival in patients with early/intermediate stage hepatocellular carcinoma |
title_short | Tissue-infiltrating lymphocytes signature predicts survival in patients with early/intermediate stage hepatocellular carcinoma |
title_sort | tissue-infiltrating lymphocytes signature predicts survival in patients with early/intermediate stage hepatocellular carcinoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549297/ https://www.ncbi.nlm.nih.gov/pubmed/31164128 http://dx.doi.org/10.1186/s12916-019-1341-6 |
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