Tertiary Lymphoid Structures Gene Signature Predicts Prognosis and Immune Infiltration Analysis in Head and Neck Squamous Cell Carcinoma

Title:Tertiary Lymphoid Structures Gene Signature Predicts Prognosis and Immune Infiltration Analysis in Head and Neck Squamous Cell Carcinoma

Volume: 25 Issue: 2

Author(s): Aiyan Xing, Dongxiao Lv, Changshun Wu, Kai Zhou, Tianhui Zhao, Lihua Zhao*, Huaqing Wang*Hong Feng*

Affiliation:

• Department of Translational Medicine, Genecast Biotechnology Co., Ltd, Wuxi, Jiangsu, 214104, China

• Department of Medical Oncology, Tianjin Union Medical Center, The Affiliated Hospital of Nankai University, Tianjin, 300000, China

• Cancer Center, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, China
• Cancer Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China

Keywords: Tertiary lymphoid structure signature, head and neck squamous cell carcinoma, immune microenvironment, driver mutations, prognosis, TP53 mutation.

Abstract:

Objectives: This study aims to assess the prognostic implications of gene signature of the tertiary lymphoid structures (TLSs) in head and neck squamous cell carcinoma (HNSCC) and scrutinize the influence of TLS on immune infiltration.

Methods: Patients with HNSCC from the Cancer Genome Atlas were categorized into high/low TLS signature groups based on the predetermined TLS signature threshold. The association of the TLS signature with the immune microenvironment, driver gene mutation status, and tumor mutational load was systematically analyzed. Validation was conducted using independent datasets (GSE41613 and GSE102349).

Results: Patients with a high TLS signature score exhibited better prognosis compared to those with a low TLS signature score. The group with a high TLS signature score had significantly higher immune cell subpopulations compared to the group with a low TLS signature score. Moreover, the major immune cell subpopulations and immune circulation characteristics in the tumor immune microenvironment were positively correlated with the TLS signature. Mutational differences in driver genes were observed between the TLS signature high/low groups, primarily in the cell cycle and NRF2 signaling pathways. Patients with TP53 mutations and high TLS signature scores demonstrated a better prognosis compared to those with TP53 wild-type. In the independent cohort, the relationship between TLS signatures and patient prognosis and immune infiltration was also confirmed. Additionally, immune-related biological processes and signaling pathways were activated with elevated TLS signature.

Conclusion: High TLS signature is a promising independent prognostic factor for HNSCC patients. Immunological analysis indicated a correlation between TLS and immune cell infiltration in HNSCC. These findings provide a theoretical basis for future applications of TLS signature in HNSCC prognosis and immunotherapy.

Cite this article as:

Xing Aiyan, Lv Dongxiao, Wu Changshun, Zhou Kai, Zhao Tianhui, Zhao Lihua*, Wang Huaqing*, Feng Hong*, Tertiary Lymphoid Structures Gene Signature Predicts Prognosis and Immune Infiltration Analysis in Head and Neck Squamous Cell Carcinoma, Current Genomics 2024; 25 (2) . https://dx.doi.org/10.2174/0113892029278082240118053857