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. 2023 Sep 13;15(18):4539.
doi: 10.3390/cancers15184539.

Prognostic Value of Necroptosis-Related Genes Signature in Oral Squamous Cell Carcinoma

Ke Huang  1   2 , Xiaoting Gu  1   2 , Huimei Xu  3 , Hui Li  2 , Mingxuan Shi  2 , Defang Wei  1   2 , Shiqi Wang  2 , Yao Li  4 , Bin Liu  2 , Yi Li  2
Affiliations

Prognostic Value of Necroptosis-Related Genes Signature in Oral Squamous Cell Carcinoma

Ke Huang et al. Cancers (Basel). .

Abstract

The dual role of necroptosis in inhibiting and promoting tumor development has gradually received much attention because of its essential significance for targeted treatment. Accordingly, this study aims to explore the relationship between necroptosis and oral squamous cell carcinoma (OSCC), and search for novel prognostic factors for OSCC. RNA-seq data and clinical information were downloaded from TCGA and GTEx databases. The prognostic signature of necroptosis-related genes (NRGs) was constructed by univariate Cox regression analysis and the LASSO Cox regression model. Moreover, survival analyses, ROC curves, and nomograms were adopted to further analyze. GO and KEGG analyses and immune infiltration analyses were used for function enrichment and immune feature research in turn. The NRG prognostic signature expression was higher in OSCC tissues than in normal tissues, and the overall survival (OS) rate of the high-expression group was much lower. HPRT1 was proved to be an independent prognostic factor in OSCC. Furthermore, the function enrichment analyses revealed that NRGs were involved in necroptosis, apoptosis, inflammation, and immune reaction. The expression of NRGs was related to immunosuppression in OSCC. Furthermore, the knockdown of HPRT1 could suppress the proliferation and migration of OSCC. In conclusion, the high expression of NRG prognostic signature is associated with poor prognosis in OSCC, and HPRT1 can serve as a novel independent prognostic factor for OSCC.

Keywords: HPRT1; biomarker; necroptosis; oral squamous cell carcinoma; prognostic signature.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Flowchart for the bioinformatics research methodology.
Figure 2
Figure 2
Venn diagram of co-expressed genes from two databases.
Figure 3
Figure 3
Univariate Cox regression analyses of the prognostic NRGs.
Figure 4
Figure 4
Selection and validation of NRGs prognostic signature with LASSO. (A) LASSO cross-validation plots of prognostic NRGs. (B) LASSO coefficients of prognostic NRGs. (C) Risk curves of high-risk and low-risk groups with OSCC based on NRGs. (D) Scatter plots comparing the survival time of OSCC patients with alive status to dead ones based on NRGs. (E) Heatmap showing the high expression of NRGs prognostic signature in OSCC contrary to normal samples. Red represents upregulated NRGs, blue represents downregulated NRGs, and white represents no significant changes. (F) KM survival curve analysis. (G) ROC curves based on NRGs at 1, 3, and 5 years.
Figure 4
Figure 4
Selection and validation of NRGs prognostic signature with LASSO. (A) LASSO cross-validation plots of prognostic NRGs. (B) LASSO coefficients of prognostic NRGs. (C) Risk curves of high-risk and low-risk groups with OSCC based on NRGs. (D) Scatter plots comparing the survival time of OSCC patients with alive status to dead ones based on NRGs. (E) Heatmap showing the high expression of NRGs prognostic signature in OSCC contrary to normal samples. Red represents upregulated NRGs, blue represents downregulated NRGs, and white represents no significant changes. (F) KM survival curve analysis. (G) ROC curves based on NRGs at 1, 3, and 5 years.
Figure 5
Figure 5
(A) The nomogram based on the expression of prognostic NRGs with vital clinical characteristics. (B) The calibration curve of the nomogram to predict the survival probability at 1, 3, and 5 years.
Figure 6
Figure 6
Univariate and multivariate Cox regression analyses of six prognostic NRGs and clinical factors.
Figure 7
Figure 7
The expressive levels and survival analyses of 6 NRGs in OSCC. (A) Differential expression analyses of non-paired samples comparing the expressive levels of 6 NRGs in OSCC and normal tissues. (B) Differential expression analyses of paired samples comparing the expressive levels of 6 NRGs in OSCC and normal tissues. (C–H) The expressive levels of HPRT1, PGAM5, BID, SMN1, FADD, and KIAA1191 in normal tissues from HPA. (I–N) The expressive levels of HPRT1, PGAM5, BID, SMN1, FADD, and KIAA1191 in OSCC patients from HPA. (O–T) The KM survival curves describe associations between overall survival and expressions of 6 NRGs. (U–Z) The ROC curves of the 6 NRGs. (ns, no significance; ***, p < 0.001).
Figure 7
Figure 7
The expressive levels and survival analyses of 6 NRGs in OSCC. (A) Differential expression analyses of non-paired samples comparing the expressive levels of 6 NRGs in OSCC and normal tissues. (B) Differential expression analyses of paired samples comparing the expressive levels of 6 NRGs in OSCC and normal tissues. (C–H) The expressive levels of HPRT1, PGAM5, BID, SMN1, FADD, and KIAA1191 in normal tissues from HPA. (I–N) The expressive levels of HPRT1, PGAM5, BID, SMN1, FADD, and KIAA1191 in OSCC patients from HPA. (O–T) The KM survival curves describe associations between overall survival and expressions of 6 NRGs. (U–Z) The ROC curves of the 6 NRGs. (ns, no significance; ***, p < 0.001).
Figure 8
Figure 8
Correlation interactive networks and GO/KEGG enrichment analyses of NRGs. (A) Protein-protein interaction (PPI) networks of 26 proteins interrelated with NRGs. (B) Network diagram of 26 genes correlated with NRGs. (C) Bubble plot of GO and KEGG enrichment analyses. (D) Network visualization of 24 NRGs with 11 potential biological functions and pathways.
Figure 9
Figure 9
Immune cell infiltration analyses of prognostic NRGs. (A) Immune infiltration analysis of HPRT1. (B) Immune infiltration analysis of BID. (C) Immune infiltration analysis of PGAM5. (D) Immune infiltration analysis of SMN1. (E) Immune infiltration analysis of FADD. (F) Immune infiltration analysis of KIAA1191.
Figure 10
Figure 10
Knockdown of HPRT1 attenuated the growth and migration capabilities of OSCC cell lines. (A) RT-qPCR demonstrated excellent knockdown efficiency of HPRT1 in both cell lines. (B) The relative cell growth rate was assessed using the CCK-8 assay. (C) Cell migration ability was evaluated using the wound healing assay. (D) Cell migration ability was assessed using the Transwell assay. (ns, no significance; *, p < 0.05).
Figure 11
Figure 11
The related mechanistic diagram based on prognostic NRGs in OSCC. The prognostic NRGs may promote the development and metastasis of OSCC by participating in the process of necroptosis, cell proliferation, compensatory stimulus, inflammatory microenvironment, and immunosuppression.
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References

    1. Bugshan A., Farooq I. Oral squamous cell carcinoma: Metastasis, potentially associated malignant disorders, etiology and recent advancements in diagnosis. F1000Research. 2020;9:229. doi: 10.12688/f1000research.22941.1. - DOI - PMC - PubMed
    1. Krishnan R.P., Pandiar D., Ramani P., Jayaraman S. Necroptosis in human cancers with special emphasis on oral squamous cell carcinoma. J. Stomatol. Oral Maxillofac. Surg. 2023:101565. doi: 10.1016/j.jormas.2023.101565. - DOI - PubMed
    1. Pandiar D., Ramani P., Krishnan R.P., Monica K. Multifaceted multinucleated giant cells in oral squamous cell carcinoma. Oral Oncol. 2021;121:105400. doi: 10.1016/j.oraloncology.2021.105400. - DOI - PubMed
    1. Jiang Y., Li T., Wu Y., Xu H., Xie C., Dong Y., Zhong L., Wang Z., Zhao H., Zhou Y., et al. GPR39 Overexpression in OSCC Promotes YAP-Sustained Malignant Progression. J. Dent. Res. 2020;99:949–958. doi: 10.1177/0022034520915877. - DOI - PubMed
    1. Pang X., Wang S.S., Zhang M., Jiang J., Fan H.Y., Wu J.S., Wang H.F., Liang X.H., Tang Y.L. OSCC cell-secreted exosomal CMTM6 induced M2-like macrophages polarization via ERK1/2 signaling pathway. Cancer Immunol. Immunother. 2021;70:1015–1029. doi: 10.1007/s00262-020-02741-2. - DOI - PMC - PubMed

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