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
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...
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | European Journal of Medical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40001-023-01568-8 |
| _version_ | 1827581727176916992 |
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| author | Jian-Di Li Yi Chen Shu-Wen Jing Li-Ting Wang Yu-Hong Zhou Zhi-Su Liu Chang Song Da-Zhi Li Hai-Quan Wang Zhi-Guang Huang Yi-Wu Dang Gang Chen Jia-Yuan Luo |
| author_facet | Jian-Di Li Yi Chen Shu-Wen Jing Li-Ting Wang Yu-Hong Zhou Zhi-Su Liu Chang Song Da-Zhi Li Hai-Quan Wang Zhi-Guang Huang Yi-Wu Dang Gang Chen Jia-Yuan Luo |
| author_sort | Jian-Di Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T22:40:31Z |
| format | Article |
| id | doaj.art-8ae265b55b8347828c6bc2b0baaeb549 |
| institution | Directory Open Access Journal |
| issn | 2047-783X |
| language | English |
| last_indexed | 2024-03-08T22:40:31Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj.art-8ae265b55b8347828c6bc2b0baaeb5492023-12-17T12:11:00ZengBMCEuropean Journal of Medical Research2047-783X2023-12-0128111910.1186/s40001-023-01568-8Triosephosphate isomerase 1 may be a risk predictor in laryngeal squamous cell carcinoma: a multi-centered study integrating bulk RNA, single-cell RNA, and protein immunohistochemistryJian-Di Li0Yi Chen1Shu-Wen Jing2Li-Ting Wang3Yu-Hong Zhou4Zhi-Su Liu5Chang Song6Da-Zhi Li7Hai-Quan Wang8Zhi-Guang Huang9Yi-Wu Dang10Gang Chen11Jia-Yuan Luo12Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous RegionDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous RegionDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous RegionDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous RegionDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous RegionDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous RegionDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous RegionDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous RegionDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous RegionDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous RegionDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous RegionDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous RegionDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous RegionAbstract 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.https://doi.org/10.1186/s40001-023-01568-8LSCCTPI1Clinicopathological significanceTumor immune microenvironmentscRNA-seqhdWGCNA |
| spellingShingle | Jian-Di Li Yi Chen Shu-Wen Jing Li-Ting Wang Yu-Hong Zhou Zhi-Su Liu Chang Song Da-Zhi Li Hai-Quan Wang Zhi-Guang Huang Yi-Wu Dang Gang Chen Jia-Yuan Luo 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 European Journal of Medical Research LSCC TPI1 Clinicopathological significance Tumor immune microenvironment scRNA-seq hdWGCNA |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | LSCC TPI1 Clinicopathological significance Tumor immune microenvironment scRNA-seq hdWGCNA |
| url | https://doi.org/10.1186/s40001-023-01568-8 |
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