Enhanced stiffness in peri-cancerous tissue - a marker of poor prognosis in papillary thyroid carcinoma with lymph node metastasis

Q: Why was tissue stiffness investigated in papillary thyroid carcinoma with lymph node metastasis?

Lymph node metastasis is an important but still controversial prognostic factor in PTC, and prior evidence suggested tissue stiffness may reflect disease aggressiveness. The study focused on whether peri-cancerous tissue stiffness relates to LNM-related invasiveness, recurrence, and mortality.

Q: What biological mechanisms were associated with higher peri-cancerous stiffness?

Higher Eshell/E in the LNM group corresponded to increased activation of cancer-associated fibroblasts (CAFs) and higher extracellular matrix component type 1 collagen (COL-I). RNA sequencing supported extracellular matrix remodeling in the LNM-Eshell/E+ subgroup.

Sep 21, 2026

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Background: The prognostic significance of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) remains controversial. Tissue stiffness has been proposed to relate to disease aggressiveness. This study aimed to assess how tissue stiffness influences LNM-related invasiveness, recurrence, and mortality in PTC patients. Method: 2492 PTC patients from 3 hospitals were stratified by pathology into LNM and non-LNM groups.

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Introduction

Enhanced stiffness in peri-cancerous tissue: a marker of poor prognosis in papillary thyroid carcinoma with lymph node metastasis Lei Hu1,‡,, Lei Ye1,‡, Chong Pei2,‡, Chunlei Sun3, Chaoxue Zhang4, Fan Jiang5, Nianan He1, Weifu Lv*,6 1Department of Ultrasound, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of People’s Republic of China, Hefei, Anhui 230001, People’s Republic of China, 2Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Hefei City, The Third Affiliated Hospital of Anhui Medical University, Hefei 230001, People’s Republic of China, 3Department of Thyroid and Breast Surgery, The First Affiliated Hospital of USTC, University of Science and Technology of People’s Republic of China, Hefei, 230001, People’s Republic of China, 4Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230001, People’s Republic of China, 5Department of Ultrasound, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230001, People’s Republic of China, 6Department of Radiology, The First Affiliated Hospital of USTC, University of Science and Technology of People’s Republic of China, Hefei 230001, People’s Republic of China *Corresponding author: Weifu Lv, Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of People’s Republic of China, Hefei, Anhui 230001, People’s Republic of People’s Republic of China ([weifulv@ustc.edu.cn](weifulv@ustc.edu.cn)) . ‡Lei Hu, Lei Ye, and Chong Pei are regarded as equal first authors. Abstract Background: The prognostic significance of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) remains controversial. Notably, there is evidence suggesting an association between tissue stiffness and the aggressiveness of the disease. We therefore aimed to explore the effect of tissue stiffness on LNM-related invasiveness in PTC patients. Method: A total of 2492 PTC patients from 3 hospitals were divided into an LNM group and a non-LNM group based on their pathological results. The effects of interior lesion stiffness (E) and peri-cancerous tissue stiffness (Eshell) on the LNM-related recurrence rate and mortality in each patient with PTC subgroup were analyzed. The activation of cancer-associated fibroblasts (CAFs) and extracellular matrix component type 1 collagen (COL-I) in the lesion were compared and analyzed across different subgroups. The underlying biological basis of differences in each subgroup was identified using RNA sequencing (RNA-seq) data. Results: The Eshell value and Eshell/E in the LNM group were significantly higher than those in the non-LNM group of patients with PTC (Eshell: 72.72 ± 5.63 vs 66.05 ± 4.46; Eshell/E: 1.20 ± 1.72 vs 1.09 ± 1.10, P < .001) . When Eshell/E > 1.412 and LNM were both present, the recurrence rate and mortality were significantly increased compared to those of group of patients with LNM (91.67% and 7.29%, respectively) . The CAF activation and COL-I content in the Eshell/E+ group were significantly higher than those in the Eshell/E − group (all P < .001), and the RNA-seq results revealed significant extracellular matrix (ECM) remodeling in the LNM-Eshell/E+ group. Conclusions: Stiff peri-cancerous tissue induced CAF activation, COL-I deposition, and ECM remodeling, resulting in a poor prognosis for PTC patients with LNM. Key words: thyroid cancer; lymph node metastasis; stiffness; peri-cancerous tissue; cancer-associated fibroblasts. Received: 3 February 2024; Accepted: 11 April 2024. © The Author(s) 2024. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)), which permits unrestricted reuse, distrib

FAQs

Why was tissue stiffness investigated in papillary thyroid carcinoma with lymph node metastasis?

Lymph node metastasis is an important but still controversial prognostic factor in PTC, and prior evidence suggested tissue stiffness may reflect disease aggressiveness. The study focused on whether peri-cancerous tissue stiffness relates to LNM-related invasiveness, recurrence, and mortality.

How were patients grouped and what stiffness metrics were analyzed?

A total of 2492 PTC patients from 3 hospitals were divided into an LNM group and a non-LNM group based on pathology results. The study analyzed interior lesion stiffness (E) and peri-cancerous tissue stiffness (Eshell), including the ratio Eshell/E, for recurrence rate and mortality.

What biological mechanisms were associated with higher peri-cancerous stiffness?

Higher Eshell/E in the LNM group corresponded to increased activation of cancer-associated fibroblasts (CAFs) and higher extracellular matrix component type 1 collagen (COL-I). RNA sequencing supported extracellular matrix remodeling in the LNM-Eshell/E+ subgroup.

Sep 21, 2026

Upload by Levi