Prognostic value of tumor stromal collagen features in patients with hepatocellular carcinoma revealed by second-harmonic generation microscopy

Liyan Lin 1, Gang Chen 2, Zhong Chen 3, Jianping Lu 2, Weifeng Zhu 2, Jing Zhong 4, Fengying Peng 2, Aimin Huang 5

Affiliations

PMID: 32735795
DOI: 10.1016/j.yexmp.2020.104513

Abstract

Introduction: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide. The search for new biomarkers that predict the outcome of HCC patients is ongoing. We propose the second harmonic generation-based quantitative assessment approach to evaluate the prognostic value of tumor stromal collagen in HCC.

Materials and methods: We evaluated tumor stromal collagen in paraffin-embedded specimens from 109 HCC patients by second-harmonic generation imaging. The parameters and quantitative assessment of collagen were obtained using a fiber network extraction algorithm. The relationships between collagen features and clinical pathological features and overall survival were statistically analyzed.

Result: Among the collagen features, some parameters of aggregated collagen correlated well with clinical pathological features, especially the aggregated collagen cross-linked density. Cross-linked collagen fibers form a fiber network in moderately and poor differentiated HCCs. Kaplan-Meier analyses and the multivariate Cox proportional hazard model showed that high aggregated collagen cross-linked density was associated with poor overall survival. The chi-squared test showed that aggregated cross-link density was significantly associated with histological grade and tumor recurrence.

Conclusion: Our results indicate the prognostic value of the quantitative evaluation of tumor stromal collagen using second harmonic generation imaging of patients with HCC.

Keywords: Collagen; Hepatocellular carcinoma; Prognosis; Second-harmonic generation.