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Annals of Surgical Oncology
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Open Access 07-12-2024 | Cytostatic Therapy | Translational Research

Survival Impacts of Mitochondrial Status in Esophageal Squamous Cell Carcinoma Patients

Authors: Kotaro Sugawara, MD, PhD, Shingo Sakashita, MD, PhD, Takashi Fukuda, MD, PhD, Chiaki Murakami, MD, PhD, Daiji Oka, MD, PhD, Gulanbar Amori, MD, PhD, Kumiko Ishibashi, MT, Yasuhito Kobayashi, MT, Hiroaki Kanda, MD, PhD, Noriko Motoi, MD, PhD

Published in: Annals of Surgical Oncology | Issue 3/2025

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Abstract

Background

Little is known about the survival impacts of mitochondrial status in esophageal squamous cell carcinoma (ESCC) patients who undergo neoadjuvant chemotherapy (NAC) followed by surgery.

Methods

In total, 260 pre-NAC samples from ESCC patients were analyzed. Mitochondrial status was estimated employing an objective, immunohistochemistry-based system (Mito-score). Mito-scores were dichotomized according to the median value of our cohort. We also evaluated the immune microenvironment (CD4, CD8, Foxp3, HLA class-1, Ki-67 and programmed death ligand-1) on pre-NAC specimens. Multivariate Cox hazards models were applied to determine independent predictors of poor overall survival (OS).

Results

Patients with cT3–4 tumors had higher Mito-scores than those with cT1–2 tumors (p = 0.06), and good responders to NAC had significantly higher Mito-scores than poor responders to NAC (p = 0.04). CD8 cells and Ki-67 expression were significantly higher in Mito-high than Mito-low tumors (p = 0.017 and p < 0.001, respectively). Patients with low Mito-scores had significantly poorer OS than those with high Mito-scores (3-year OS: 57.6% vs. 68.2%; p = 0.03). A survival difference by Mito-score was evident in cStage III–IV patients (3-year OS: low 50.6% vs. high 66.1%; p = 0.006). Multivariable analysis revealed that a low Mito-score (hazard ratio 1.59, 95% confidence interval 1.12–2.24; p = 0.009) as well as pT3–4 disease (p < 0.001) and pN2–3 disease (p < 0.001) were independently associated with poor OS outcomes.

Conclusions

A low Mito-score before NAC had a significant survival impact in ESCC patients, especially in those with advanced disease. Mitochondrial status might be associated with tumor aggressiveness and responsiveness to NAC, thereby possibly affecting the survival outcomes of ESCC patients.
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Metadata
Title
Survival Impacts of Mitochondrial Status in Esophageal Squamous Cell Carcinoma Patients
Authors
Kotaro Sugawara, MD, PhD
Shingo Sakashita, MD, PhD
Takashi Fukuda, MD, PhD
Chiaki Murakami, MD, PhD
Daiji Oka, MD, PhD
Gulanbar Amori, MD, PhD
Kumiko Ishibashi, MT
Yasuhito Kobayashi, MT
Hiroaki Kanda, MD, PhD
Noriko Motoi, MD, PhD
Publication date
07-12-2024
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 3/2025
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-024-16533-w

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