Background: Lymph node metastasis (LNM) is a critical factor affecting the outcomes of head and neck squamous cell carcinoma (HNSCC) and the main reason for treatment failure. This study was designed to examine the effects of the key genes involved in the LNM of HNSCC.
Methods: Tissue samples (HNSCC) were examined by transcriptome sequencing, and the core genes associated with LNM were detected via bioinformatics analysis. The functions of these core genes were then validated using the TCGA biological database and their effects on the propagation, invasion, and metastasis of HNSCC cells were evaluated through cell culture experiments. Moreover, the effect of core gene expression on the LNM capability of HNSCC was confirmed via a footpad xenograft mice model.
Results: In the findings, a key gene involved in the LNM of HNSCC was identified as SLC7A2. It was correlated with adverse clinical prognosis and expressed with low expression in HNSCC tissues. As shown in cell culture experiments, FaDu and SCC15 cell growth, invasion, and migration were inhibited when SLC7A2 was overexpressed. Further, cell apoptosis was stimulated, and lymphangiogenesis was suppressed through the downregulation of CPB2 expression. Animal studies demonstrated that the growth and LNM of HNSCC cells were inhibited by SLC7A2 overexpression.
Conclusion: It is concluded that SLC7A2 is involved in HNSCC lymphatic metastasis by controlling CPB2 function. The results are anticipated to offer new directions for the effective treatment of HNSCC.
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http://dx.doi.org/10.1002/cam4.70273 | DOI Listing |
Mol Cancer Res
January 2025
Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Malignant neoplasms arise within a region of chronic inflammation caused by tissue injuries. Inflammation is a key factor involved in all aspects of tumorigenesis including initiation, proliferation, invasion, angiogenesis, and metastasis. Interleukin-1 (IL-1) plays critical functions in tumor development with influencing the tumor microenvironment and promoting cancer progression.
View Article and Find Full Text PDFHead and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. HPV-negative HNSCC, which arises in the upper airway mucosa, is particularly aggressive, with nearly half of patients succumbing to the disease within five years and limited response to immune checkpoint inhibitors compared to other cancers. There is a need to further explore the complex immune landscape in HPV-negative HNSCC to identify potential therapeutic targets.
View Article and Find Full Text PDFBackground: For patients with head and neck squamous cell carcinoma (HNSCC), failure of definitive radiation combined with cisplatin nearly universally results in death. Although hyperactivation of the Nrf2 pathway can drive radiation and cisplatin resistance along with suppressed anti-tumor immunity, treatment-refractory HNSCC tumors may retain sensitivity to targeted agents secondary to synergistic lethality with other oncogenic drivers (e.g.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Head and Neck Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Fukuoka, Japan.
Background: Nivolumab paved a new way in the treatment of patients with recurrent or metastatic (RM) head and neck squamous cell carcinoma (RM-HNSCC). However, the limited rates of long-term survivors (< 20%) demand a robust prognostic biomarker. This nationwide multi-centric prospective study aimed to identify a plasma exosome (PEX) mRNA signature, which serves as a companion diagnostic of nivolumab and provides a biological clue to develop effective therapies for a majority of non-survivors.
View Article and Find Full Text PDFClin Transl Radiat Oncol
March 2025
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
Aim: This study leveraged standard-of-care CT scans of patients receiving unilateral radiotherapy (RT) for early tonsillar cancer to detect volumetric changes in the carotid arteries, and determine whether there is a dose-response relationship.
Methods: Disease-free cancer survivors (>3 months since therapy and age > 18 years) treated with intensity modulated RT for early (T1-2, N0-2b) tonsillar cancer with pre- and post-therapy contrast-enhanced CT scans available were included. Patients treated with definitive surgery, bilateral RT, or additional RT before the post-RT CT scan were excluded.
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