The role of SPP1 as a prognostic biomarker and therapeutic target in head and neck squamous cell carcinoma

Cai, Xinjia; Zhang, H.; Li, T.

doi:10.1016/j.ijom.2021.07.022

Cited by 11 publications

(7 citation statements)

References 67 publications

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“…The ROC curve analysis showed that the area under the curve that distinguished OLK from OSCC was 0.745 (CI = 0.638–0.851), which had a certain diagnostic accuracy ( Figure 7(f) ). By comparison, this diagnostic model had the highest diagnostic efficiency in previous studies [ 6 , 7 , 17 – 21 ] ( Table 4 ), and the ROC curve is shown in Figures 7(g) – 7(m) .…”

Section: Resultsmentioning

confidence: 74%

“…Currently, there are no clear diagnostic methods to predict whether OLK would become cancer. Cai et al [ 6 ] found that SPP1 increased as normal tissues progressed to OLK and OSCC tissues. Fernanda Herrera Costa et al [ 7 ] found that ALDH1A1 was positive in OLK tissues and negative in OSCC tissues, while ALDH1A2 was negative in OLK tissues and positive in OSCC tissues, which can be used as potential biomarkers for early detection of OSCC.…”

Section: Introductionmentioning

confidence: 99%

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Identification of Biomarkers Associated with Cancerous Change in Oral Leukoplakia Based on Integrated Transcriptome Analysis

Chun-shen

Shi

Zuo

et al. 2022

Journal of Oncology

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Objective. Oral leukoplakia (OLK) is the most common precancerous lesion in the oral cavity. This study aimed to explore key biomarkers for monitoring OLK for early diagnosis of oral squamous cell carcinoma (OSCC) and screen small-molecule drugs for the prevention of OSCC. Method. The Gene Expression Omnibus (GEO) database was explored to extract two microarray datasets, namely, GSE85195 and GSE25099. The data of the normal group, OLK group, and OSCC group were analyzed by weighted gene coexpression network analysis (WGCNA) to identify the most significant gene module and differentially expressed genes (DEGs). The intersection genes were extracted as the key genes of OLK carcinogenesis. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed in the module. Connectivity Map and molecular docking were used to screen small-molecule drugs. The diagnostic values of four key genes were identified and verified in the GSE26549 dataset. Results. WGCNA obtained the red module (r = −0.91, p < 0.05 ) with the strongest correlation with cancerous phenotype. GO enrichment analysis showed 60 pathways, including 28 biological processes, 11 cell components, and 21 molecular functions, and KEGG enrichment analysis showed 4 pathways ( p < 0.05 ). In the differential expression analysis, there was no intersection between the upregulated genes and the red module genes. However, the intersection of the downregulated genes and the red module genes yielded 4 key genes: dopachrome tautomerase (DCT), keratin 3 (KRT3), keratin 76 (KRT76), and FAM3 metabolic regulation signal molecule B (FAM3B). The area under the curve of the diagnostic model constructed by these four genes was 0.963 (CI = 0.913–1.000). The sensitivity was 0.933, and the specificity was 0.923. The diagnostic model was successfully verified in GSE26549 (AUC = 0.745, CI = 0.638–0.851). Compared with the diagnostic models of the previous studies, the diagnostic efficiency of this model was the highest. The small-molecule drugs, selumetinib and benidipine, were selected according to the gene expression profile and showed binding activity when docking with the above molecules. Conclusions. This study provides new targets and drugs for OLK. These targets could be used as the key diagnostic molecules for long-term follow-up of OLK. The small-molecule drugs selumetinib and benidipine could be used for the prevention and treatment of OSCC.

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Section: Resultsmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Identification of Biomarkers Associated with Cancerous Change in Oral Leukoplakia Based on Integrated Transcriptome Analysis

Chun-shen

Shi

Zuo

et al. 2022

Journal of Oncology

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“…Moreover, pro-inflammatory M1-macrophages were identified in the metastatic lymph node, with high TIMP1 expression in a subset of the cells. Cancer-associated macrophages (CAM) exhibited strong secreted phosphoprotein 1 ( SPP1) expression, a gene implicated in macrophage polarity and previously associated with negative human papillomavirus (HPV) status and poor prognosis in HNSCC 37 . This cluster was found to frequently colocalize with tumor cells, highlighting their interactive potential in the tissue microenvironment (TME).…”

Section: Resultsmentioning

confidence: 99%

Open-ST: High-resolution spatial transcriptomics in 3D

Schott,

León-Periñán,

Splendiani

et al. 2023

Preprint

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Spatial transcriptomics (ST) methods have been developed to unlock molecular mechanisms underlying tissue development, homeostasis, or disease. However, there is a need for easy-to-use, high-resolution, cost-efficient, and 3D-scalable methods. Here, we report Open-ST, a sequencing-based, open-source experimental and computational resource to address these challenges and to study the molecular organization of tissues in 3D. In mouse brain, Open-ST captured transcripts at subcellular resolution and reconstructed cell types. In primary tumor and patient-matched healthy/metastatic lymph nodes, Open-ST captured the diversity of immune, stromal and tumor populations in space. Distinct cell states were organized around cell-cell communication hotspots in the tumor, but not the metastasis. Strikingly, the 3D reconstruction and multimodal analysis of the metastatic lymph node revealed spatially contiguous structures not visible in 2D and potential biomarkers precisely at the 3D tumor/lymph node boundary. We anticipate Open-ST to accelerate the identification of spatial molecular mechanisms in 2D and 3D.

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“…It is associated with tumor invasion and metastasis, apoptosis inhibition, angiogenesis, and chemotherapy resistance [ 31 ]. The level of SPP1 mRNA in HNSCC was higher than that in noncancerous tissues, and high SPP1 mRNA level was associated with poor overall survival of HNSCC patients [ 32 ]. Another study showed that the serum SPP1 level of HNSCC with positive cervical lymph nodes was significantly higher than that with negative cervical lymph nodes, and researchers concluded that SPP1 might play an essential role in developing cervical lymph nodes metastasis in NHSCC patients [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

A Four-Gene Signature Associated with Radioresistance in Head and Neck Squamous Cell Carcinoma Identified by Text Mining and Data Analysis

Zhang

Wang

et al. 2022

Computational and Mathematical Methods in Medicine

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Purpose. Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer globally, and radiotherapy plays a crucial part in its treatment. This study was designed to identify potential genes related to radiation resistance in HNSCC. Method. We first used text mining to obtain common genes related to radiotherapy resistance and HNSCC in published articles. Functional enrichment analyses were conducted to identify the significantly enriched pathways and genes. Protein and protein interactions were performed, and the most significant gene modules were determined; then, genes in the gene modules were validated at transcriptional levels and overall survival. Gene set variation analysis (GSVA) score was calculated, and the association between GSVA score and survival/pathway was estimated. Immune cell infiltration, methylation, and genetic alteration analysis of these genes was conducted in HNSCC patients. Finally, potential sensitive anticancer drugs related to target genes were obtained. Result. We identified 583 common genes through text mining. After further validation, a four-gene signature (EPHB2, SPP1, SERPINE1, and VEGFC) was constructed. The patients with higher GSVA scores have a worse prognosis than those with lower GSVA scores. Differences in methylation of these four genes in HNSCC tumor tissue and normal tissue were compared, with higher methylation levels of EBPH2 and SPP1 in normal tissue and higher methylation levels of SERPINE1 in the tumor. Immune cell infiltration revealed that the increased expression of these genes was closely related to the infiltration level of CD4+ T cell, neutrophil, macrophage, and dendritic cell. Thirty drugs, including 22 positively and eight negatively correlated drugs that most correlated with related genes, were available for treating HNSCC. Conclusion. In this study, we identified four potential genes as well as corresponding drugs that might be related to radioresistance in HNSCC patients. These candidate genes may provide a promising avenue to further elevate radiotherapy efficacy.

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The role of SPP1 as a prognostic biomarker and therapeutic target in head and neck squamous cell carcinoma

Cited by 11 publications

References 67 publications

Identification of Biomarkers Associated with Cancerous Change in Oral Leukoplakia Based on Integrated Transcriptome Analysis

Identification of Biomarkers Associated with Cancerous Change in Oral Leukoplakia Based on Integrated Transcriptome Analysis

Open-ST: High-resolution spatial transcriptomics in 3D

A Four-Gene Signature Associated with Radioresistance in Head and Neck Squamous Cell Carcinoma Identified by Text Mining and Data Analysis

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