# Inflammation as a mediator between neck adipose tissue and tumor aggressiveness in hypopharyngeal and laryngeal squamous cell carcinoma

**Authors:** Yu Jiang, Xiaodong Ji, Shanshan Gao, Xiaohuang Yang, Qing Li, Zhuo Yu, Xilong Yang, Zhuo Shen, Jie Shen, Shuang Xia

PMC · DOI: 10.1186/s40644-025-00913-w · Cancer Imaging · 2025-07-29

## TL;DR

Lower neck fat and higher inflammation are linked to more aggressive throat cancers, especially in men.

## Contribution

Identifies a NAT-inflammation-aggressiveness axis in hypopharyngeal and laryngeal cancers.

## Key findings

- Lower NAT is linked to advanced cancer stages and local invasion.
- Higher dNLR correlates with worse cancer outcomes like metastasis.
- dNLR partially explains the link between NAT and tumor aggressiveness.

## Abstract

The impact of neck adipose tissue (NAT) on the invasiveness of hypopharyngeal squamous cell carcinoma (HPSCC) and laryngeal squamous cell carcinoma (LSCC) remains uncertain. We investigated the roles of NAT and derived - neutrophil to lymphocyte ratio (dNLR) in the aggressiveness of HPSCC and LSCC, and established an adipose- inflammation-aggressiveness axis to identify high-risk factors.

This retrospective study involved 412 patients with HPSCC or LSCC. Clinical characteristics, body mass index (BMI), NAT and dNLR were collected and calculated. Logistic regression models, restricted cubic splines (RCS) and mediation analysis were employed to evaluate the associations between NAT, dNLR and the aggressiveness of HPSCC and LSCC.

The cohort included 412 patients (mean age, 63 years; 93.69% male). Lower NAT was independently associated with advanced TNM stage (adjusted Odds Ratio [OR], 0.54; p = 0.015) and tumor local invasion (adjusted OR, 0.53; p = 0.008). Higher dNLR was significantly associated with advanced TNM stage (adjusted OR, 3.26; p < 0.001), lymph node metastasis (LNM) (adjusted OR, 1.40; p = 0.021), and tumor local invasion (adjusted OR, 2.29; p < 0.001). NAT showed a modest negative correlation with dNLR (R = -0.138, p = 0.005). Mediation analysis indicated that dNLR partially mediated the relationship between NAT and tumor aggressiveness.

Reduced NAT is associated with increased tumor aggressiveness in HPSCC and LSCC, and this relationship may be partially mediated by elevated dNLR. The association appeared more pronounced in male patients. These findings suggest that local adiposity and inflammation may play a role in tumor behavior and warrant further investigation in future studies.

The online version contains supplementary material available at 10.1186/s40644-025-00913-w.

## Linked entities

- **Diseases:** hypopharyngeal squamous cell carcinoma (MONDO:0044638), laryngeal squamous cell carcinoma (MONDO:0005595)

## Full-text entities

- **Genes:** PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1) [NCBI Gene 5562] {aka AMPK, AMPK alpha 1, AMPKa1}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, PPARA (peroxisome proliferator activated receptor alpha) [NCBI Gene 5465] {aka NR1C1, PPAR, PPAR-alpha, PPARalpha, hPPAR}, ADIPOQ (adiponectin, C1Q and collagen domain containing) [NCBI Gene 9370] {aka ACDC, ACRP30, ADIPQTL1, ADPN, APM-1, APM1}, THBS1 (thrombospondin 1) [NCBI Gene 7057] {aka THBS, THBS-1, TSP, TSP-1, TSP1}, TENM1 (teneurin transmembrane protein 1) [NCBI Gene 10178] {aka ODZ1, ODZ3, TEN-M1, TEN1, TNM, TNM1}, FGF21 (fibroblast growth factor 21) [NCBI Gene 26291], CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, SAT1 (spermidine/spermine N1-acetyltransferase 1) [NCBI Gene 6303] {aka DC21, KFSD, KFSDX, SAT, SSAT, SSAT-1}
- **Diseases:** necrosis (MESH:D009336), Thyroid cartilage (MESH:D002357), LNM (MESH:D008207), metabolic disorder (MESH:D008659), ACME (MESH:C567355), Chronic inflammation (MESH:D007249), overweight (MESH:D050177), Tumor (MESH:D009369), adipose (MESH:D018205), HPSCC (MESH:D000077195), sclerosis (MESH:D012598), Neck (MESH:D006258), aggressiveness (MESH:D010554), obese (MESH:D009765), renal cell carcinoma (MESH:D002292), RCS (MESH:D002313), systemic (MESH:D015619)
- **Chemicals:** dNLR (-), Alcohol (MESH:D000438)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12309162/full.md

## References

2 references — full list in the complete paper: https://tomesphere.com/paper/PMC12309162/full.md

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Source: https://tomesphere.com/paper/PMC12309162