Triosephosphate isomerase 1 may be a risk predictor in laryngeal squamous cell carcinoma: a multi-centered study integrating bulk RNA, single-cell RNA, and protein immunohistochemistry
-
Published:2023-12-15
Issue:1
Volume:28
Page:
-
ISSN:2047-783X
-
Container-title:European Journal of Medical Research
-
language:en
-
Short-container-title:Eur J Med Res
Author:
Li Jian-Di,Chen Yi,Jing Shu-Wen,Wang Li-Ting,Zhou Yu-Hong,Liu Zhi-Su,Song Chang,Li Da-Zhi,Wang Hai-Quan,Huang Zhi-Guang,Dang Yi-Wu,Chen Gang,Luo Jia-Yuan
Abstract
Abstract
Background
Although great progress has been made in anti-cancer therapy, the prognosis of laryngeal squamous cell carcinoma (LSCC) patients remains unsatisfied. Quantities of studies demonstrate that glycolytic reprograming is essential for the progression of cancers, where triosephosphate isomerase 1 (TPI1) serves as a catalytic enzyme. However, the clinicopathological significance and potential biological functions of TPI1 underlying LSCC remains obscure.
Methods
We collected in-house 82 LSCC tissue specimens and 56 non-tumor tissue specimens. Tissue microarrays (TMA) and immunohistochemical (IHC) experiments were performed. External LSCC microarrays and bulk RNA sequencing data were integrated to evaluate the expression of TPI1. We used a log-rank test and the CIBERSORT algorithm to assess the prognostic value of TPI1 and its association with the LSCC microenvironment. Malignant laryngeal epithelial cells and immune-stromal cells were identified using inferCNV and CellTypist. We conducted a comprehensive analysis to elucidate the molecular functions of TPI1 in LSCC tissue and single cells using Pearson correlation analysis, high dimensional weighted gene co-expression analysis, gene set enrichment analysis, and clustered regularly interspaced short palindromic repeats (CRISPR) screen. We explored intercellular communication patterns between LSCC single cells and immune-stromal cells and predicted several therapeutic agents targeting TPI1.
Results
Based on the in-house TMA and IHC analysis, TPI1 protein was found to have a strong positive expression in the nucleus of LSCC cells but only weakly positive activity in the cytoplasm of normal laryngeal cells (p < 0.0001). Further confirmation of elevated TPI1 mRNA expression was obtained from external datasets, comparing 251 LSCC tissue samples to 136 non-LSCC tissue samples (standardized mean difference = 1.06). The upregulated TPI1 mRNA demonstrated a high discriminative ability between LSCC and non-LSCC tissue (area under the curve = 0.91; sensitivity = 0.87; specificity = 0.79), suggesting its potential as a predictive marker for poor prognosis (p = 0.037). Lower infiltration abundance was found for plasma cells, naïve B cells, monocytes, and neutrophils in TPI-high expression LSCC tissue. Glycolysis and cell cycle were significantly enriched pathways for both LSCC tissue and single cells, where heat shock protein family B member 1, TPI1, and enolase 1 occupied a central position. Four outgoing communication patterns and two incoming communication patterns were identified from the intercellular communication networks. TPI1 was predicted as an oncogene in LSCC, with CRISPR scores less than -1 across 71.43% of the LSCC cell lines. TPI1 was positively correlated with the half maximal inhibitory concentration of gemcitabine and cladribine.
Conclusions
TPI1 is dramatically overexpressed in LSCC than in normal tissue, and the high expression of TPI1 may promote LSCC deterioration through its metabolic and non-metabolic functions. This study contributes to advancing our knowledge of LSCC pathogenesis and may have implications for the development of targeted therapies in the future.
Funder
Guangxi Medical University Student Innovation and Entrepreneurship Training Program Project Guangxi Higher Education Undergraduate Teaching Reform Project Guangxi Educational Science Planning Key Project Guangxi Medical High-level Key Talents Training "139" Program Guangxi Medical University Teacher Teaching Ability Development Project
Publisher
Springer Science and Business Media LLC
Reference55 articles.
1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA. 2021;71(3):209–49. 2. Xia C, Dong X, Li H, Cao M, Sun D, He S, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J. 2022;135(5):584–90. 3. Wang P, Li GY, Zhou L, Jiang HL, Yang Y, Wu HT. Exosomes from M2 macrophages promoted glycolysis in FaDu cells by inhibiting PDLIM2 expression to stabilize PFKL. Neoplasma. 2022;69:5. 4. Liberale C, Soloperto D, Marchioni A, Monzani D, Sacchetto L. Updates on larynx cancer: risk factors and oncogenesis. Int J Mol Sci. 2023;24:16. 5. Huang Q, Guo Y, Shen Y, Hsueh CY, Tao L, Zhang M, et al. Epidemiological, clinical, and oncological outcomes of non-alcohol drinking and non-smoking laryngeal squamous cell carcinoma patients: a distinct entity. Technol Cancer Res Treat. 2022;21:15330338221133690.
|
|