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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	2237
Number of pages	16
Journal	Cancers
Volume	14
Issue number	9
DOIs	https://doi.org/10.3390/cancers14092237
Publication status	Published - 29 Apr 2022

Keywords

CHOLANGIOCARCINOMA
COLORECTAL-CANCER
CRITERIA
HEPATIC RESECTION
NEUROGENESIS
NEURONS
PERINEURAL INVASION
SURVIVAL
SYSTEM
biomarker
hepatocellular carcinoma
nerve fibers
oncological outcome
tumor microenvironment

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@article{f31ea24fadb9477ba652a62c80047ca2,

title = "Limitations of Nerve Fiber Density as a Prognostic Marker in Predicting Oncological Outcomes in Hepatocellular Carcinoma",

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 = "CHOLANGIOCARCINOMA, COLORECTAL-CANCER, CRITERIA, HEPATIC RESECTION, NEUROGENESIS, NEURONS, PERINEURAL INVASION, SURVIVAL, SYSTEM, biomarker, hepatocellular carcinoma, nerve fibers, oncological outcome, tumor microenvironment",

author = "Jan Bednarsch and Xiuxiang Tan and Zoltan Czigany and Georg Wiltberger and Buelow, {Roman David} and Peter Boor and Lang, {Sven Arke} and Ulmer, {Tom Florian} and Neumann, {Ulf Peter} and Heij, {Lara Rosaline}",

note = "Funding Information: 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). Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = apr,

day = "29",

doi = "10.3390/cancers14092237",

language = "English",

volume = "14",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "9",

}

TY - JOUR

T1 - Limitations of Nerve Fiber Density as a Prognostic Marker in Predicting Oncological Outcomes in Hepatocellular Carcinoma

AU - Bednarsch, Jan

AU - Tan, Xiuxiang

AU - Czigany, Zoltan

AU - Wiltberger, Georg

AU - Buelow, Roman David

AU - Boor, Peter

AU - Lang, Sven Arke

AU - Ulmer, Tom Florian

AU - Neumann, Ulf Peter

AU - Heij, Lara Rosaline

N1 - Funding Information: 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). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/4/29

Y1 - 2022/4/29

N2 - 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.

AB - 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.

KW - CHOLANGIOCARCINOMA

KW - COLORECTAL-CANCER

KW - CRITERIA

KW - HEPATIC RESECTION

KW - NEUROGENESIS

KW - NEURONS

KW - PERINEURAL INVASION

KW - SURVIVAL

KW - SYSTEM

KW - biomarker

KW - hepatocellular carcinoma

KW - nerve fibers

KW - oncological outcome

KW - tumor microenvironment

U2 - 10.3390/cancers14092237

DO - 10.3390/cancers14092237

M3 - Article

C2 - 35565366

SN - 2072-6694

VL - 14

JO - Cancers

JF - Cancers

IS - 9

M1 - 2237

ER -