The heterogenic tumor microenvironment of hepatocellular carcinoma and prognostic analysis based on tumor neo-vessels, macrophages and α-SMA

Fang,Min; Yuan,Jingping; Chen,Mengyuan; Sun,Zongwen; Liu,Lulu; Cheng,Guoping; Ying,Hangjie; Yang,Shifeng; Chen,Ming

doi:10.3892/ol.2018.7946

The heterogenic tumor microenvironment of hepatocellular carcinoma and prognostic analysis based on tumor neo-vessels, macrophages and α-SMA

Authors:
- Min Fang
- Jingping Yuan
- Mengyuan Chen
- Zongwen Sun
- Lulu Liu
- Guoping Cheng
- Hangjie Ying
- Shifeng Yang
- Ming Chen
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Affiliations: Department of Radiation Oncology, Zhejiang Cancer Hospital, Zhejiang Key Laboratory of Radiation Oncology & College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310022, P.R. China, Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Oncology, The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China, Department of Oncology, Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China, Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
Published online on: February 5, 2018 https://doi.org/10.3892/ol.2018.7946
Pages: 4805-4812
Copyright: © Fang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study was performed to quantify tumor neo-vessels, macrophages and fibroblasts in the tumor microenvironment of hepatocellular carcinoma (HCC) and explore the prognostic factors of HCC. The distribution of tumor neo-vessels, macrophages and fibroblasts was quantified by immunohistochemistry and inverted microscopy with the CRi Nuance multispectral imaging system, and the correlation of these parameters with the clinico‑pathological characteristics and overall survival of the patients was analyzed. The number of tumor neo‑vessels and macrophages, and density of the fibroblasts, as calculated by the thickness of the tumor stroma in the tumor microenvironment, ranged from 51‑429 (median, 218), 110‑555 (median, 259) and 35.6‑555.5 µm (median, 247.0), respectively. Using the median values as a cutoff, the cases were stratified into high‑ and low‑density groups. Survival analysis demonstrated that the high‑density groups regarding macrophages (χ2=5.249, P=0.022) and fibroblasts (χ2=18.073, P<0.001) had a significantly shorter disease‑free survival (DFS) than the low‑density groups. The high‑density tumor neo‑vessel group had a shorter DFS with a median of 5 months than the low‑density group with a median of 7 months; however, there was no statistical significance between these two groups (χ2=1.663, P=0.197). Regarding the above three stromal components combined, all of the cases were classified into low‑, middle‑ and high‑density groups. Survival analysis demonstrated that the high‑density group of stromal components had a shorter DFS than the other two groups with a median of 3 months (χ2=14.439, P=0.001). Multivariate analysis by Cox regression indicated that cirrhosis, metastasis stage, as well as macrophage and fibroblast density were independent prognostic factors. In conclusion, the key elements in the tumor microenvironment, including tumor neo‑vessels, macrophages and fibroblasts, were heterogenic in HCC tissues and have significant roles in HCC invasion and metastasis. Stromal components are associated with the prognosis of patients with HCC; the higher the density of stromal components, the poorer the prognosis of patients with HCC.

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