Limitations of Nerve Fiber Density as a Prognostic Marker in Predicting Oncological Outcomes in Hepatocellular Carcinoma

Jan Bednarsch; Xiuxiang Tan; Zoltan Czigany; Georg Wiltberger; Roman David Buelow; Peter Boor; Sven Arke Lang; Tom Florian Ulmer; Ulf Peter Neumann; Lara Rosaline Heij

doi:10.3390/cancers14092237

Limitations of Nerve Fiber Density as a Prognostic Marker in Predicting Oncological Outcomes in Hepatocellular Carcinoma

Cancers (Basel). 2022 Apr 29;14(9):2237. doi: 10.3390/cancers14092237.

Authors

Jan Bednarsch¹, Xiuxiang Tan^{1

2}, Zoltan Czigany¹, Georg Wiltberger¹, Roman David Buelow³, Peter Boor^{3

4}, Sven Arke Lang¹, Tom Florian Ulmer¹, Ulf Peter Neumann^{1

5}, Lara Rosaline Heij^{1

2

3}

Affiliations

¹ Department of Surgery and Transplantation, University Hospital RWTH Aachen, 52074 Aachen, Germany.
² NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6229 ER Maastricht, The Netherlands.
³ Institute of Pathology, University Hospital RWTH Aachen, 52074 Aachen, Germany.
⁴ Department of Nephrology and Immunology, University Hospital RWTH Aachen, 52074 Aachen, Germany.
⁵ Department of Surgery, UMC+ Maastricht University Hospital, 6229 HX Maastricht, The Netherlands.

Abstract

It has been shown that the presence and density of nerve fibers (NFs; NFD) in the tumor microenvironment (TME) may play an important prognostic role in predicting long-term oncological outcomes in various malignancies. However, the role of NFD in the prognosis of hepatocellular carcinoma (HCC) is yet to be explored. To this end, we aimed to investigate the impact of NFs on oncological outcomes in a large European single-center cohort of HCC patients. In total, 153 HCC patients who underwent partial hepatectomy in a curative-intent setting between 2010 and 2021 at our university hospital were included in this study. Group comparisons between patients with and without NFs were conducted and the association of recurrence-free survival (RFS) and overall survival (OS) with the presence of NFs and other clinico-pathological variables were determined by univariate and multivariable Cox regression models. Patients with NFs in the TME presented with a median OS of 66 months (95% CI: 30−102) compared to 42 months (95% CI: 20−63) for patients without NFs (p = 0.804 log-rank). Further, RFS was 26 months (95% CI: 12−40) for patients with NFs compared to 18 months (95% CI: 9−27) for patients without NFs (p = 0.666 log-rank). In a subgroup analysis, patients with NFD ≤ 5 showed a median OS of 54 months (95% CI: 11−97) compared to 48 months (95% CI: 0−106) for the group of patients with NFD > 5 (p = 0.787 log-rank). Correspondingly, the RFS was 26 months (95% CI: 10−42) in patients with NFD ≤ 5 and 29 months (95% CI: 14−44) for the subcohort with NFD > 5 (p = 0.421 log-rank). Further, group comparisons showed no clinico-pathological differences between patients with NFs (n = 76) and without NFs (n = 77) and NFs were not associated with OS (p = 0.806) and RFS (p = 0.322) in our Cox regression models. In contrast to observations in various malignancies, NFs in the TME and NFD are not associated with long-term oncological outcomes in HCC patients undergoing surgery.

Keywords: biomarker; hepatocellular carcinoma; nerve fibers; oncological outcome; tumor microenvironment.

Grants and funding

This particular research received no external funding. X.T. received a scholarship from the China Scholarship Council (CSC Grant No: 201806210074). This project was supported by the German Research Foundation (SFB-CRC 1382-A01).