Background: The clinical significance and role of glycan synthase glucosamine (N-acetyl) transferase 3 (GCNT3) has not been investigated in lung squamous cell carcinoma (LUSC).
Materials & Methods: In the present study, multiple detection technologies including tissue microarrays, external microarrays and RNA-seq were adopted for evaluating the clinic-pathological significance of GCNT3 in 1632 LUSC samples and 1478 non-cancer samples. Standard mean difference and hazard ratio value were calculated from all included datasets for assessing differential expression and prognostic value of GCNT3 in LUSC. The molecular basis underlying GCNT3 in LUSC was also explored through methylation level, genetic mutation and functional enrichment analysis of GCNT3-correlated genes in LUSC.
Results: GCNT3 was obviously upregulated in LUSC samples. GCNT3 overexpression exerted unfavorable impact on the progression-free survival and overall survival of LUSC patients from GSE29013. The mRNA expression of GCNT3 was negatively correlated with methylation level of GCNT3 in LUSC and the predominant type of genetic alteration for GCNT3 in LUSC was mRNA high. Genes correlated with GCNT3 in LUSC mainly assembled in pathways such as adherens junction, p53 signaling pathway, protein digestion and absorption pathway.
Conclusions: In conclusion, overexpressed GCNT3 had clinical potential as therapeutic target for LUSC.

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This is a list of supplementary files associated with this preprint. Click to download.
The discriminatory ability of GCNT3 expression in distinguishing lung squamous cell carcinoma from non-cancer tissues in each microarray and RNA-seq dataset. AUC: area under curve.
Flow chart of choosing qualified microarrays or RNA-seq datasets.
Distinguishing capacity of GCNT3 in lung squamous cell carcinoma for in-house tissue microarray, external microarrays and RNA-seq datasets. A. SROC curves; B. Forest plot of sensitivity; C. Forest plot of specificity; D. Forest plot of positive likelihood ratio; E. Forest plot of negative likelihood ratio.
Pooled porgnostic forest plot of GCNT3 in lung squamous cell carcinoma for external microarrays and RNA-seq datasets. A: Forest plot for hazard ratio of overall survival; B. Forest plot for hazard ratio of recurrence-free survival; C. Forest plot for hazard ratio of relapse-free survival. HR: hazard ratio.
Venn plots of genes positively or negatively correlated with GCNT3 in lung squamous cell carcinoma. A. The intersection of upregulated DEGs (blue) and genes showed positive correlation with GCNT3 in at least one dataset (red) of lung squamous cell carcinoma. B. The intersection of downregulated DEGs (blue) and genes concurrently showed negative correlation with GCNT3 in at least one datasets (red) of lung squamous cell carcinoma.
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Posted 13 Jan, 2021
Posted 13 Jan, 2021
Background: The clinical significance and role of glycan synthase glucosamine (N-acetyl) transferase 3 (GCNT3) has not been investigated in lung squamous cell carcinoma (LUSC).
Materials & Methods: In the present study, multiple detection technologies including tissue microarrays, external microarrays and RNA-seq were adopted for evaluating the clinic-pathological significance of GCNT3 in 1632 LUSC samples and 1478 non-cancer samples. Standard mean difference and hazard ratio value were calculated from all included datasets for assessing differential expression and prognostic value of GCNT3 in LUSC. The molecular basis underlying GCNT3 in LUSC was also explored through methylation level, genetic mutation and functional enrichment analysis of GCNT3-correlated genes in LUSC.
Results: GCNT3 was obviously upregulated in LUSC samples. GCNT3 overexpression exerted unfavorable impact on the progression-free survival and overall survival of LUSC patients from GSE29013. The mRNA expression of GCNT3 was negatively correlated with methylation level of GCNT3 in LUSC and the predominant type of genetic alteration for GCNT3 in LUSC was mRNA high. Genes correlated with GCNT3 in LUSC mainly assembled in pathways such as adherens junction, p53 signaling pathway, protein digestion and absorption pathway.
Conclusions: In conclusion, overexpressed GCNT3 had clinical potential as therapeutic target for LUSC.

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8
This is a list of supplementary files associated with this preprint. Click to download.
The discriminatory ability of GCNT3 expression in distinguishing lung squamous cell carcinoma from non-cancer tissues in each microarray and RNA-seq dataset. AUC: area under curve.
Flow chart of choosing qualified microarrays or RNA-seq datasets.
Distinguishing capacity of GCNT3 in lung squamous cell carcinoma for in-house tissue microarray, external microarrays and RNA-seq datasets. A. SROC curves; B. Forest plot of sensitivity; C. Forest plot of specificity; D. Forest plot of positive likelihood ratio; E. Forest plot of negative likelihood ratio.
Pooled porgnostic forest plot of GCNT3 in lung squamous cell carcinoma for external microarrays and RNA-seq datasets. A: Forest plot for hazard ratio of overall survival; B. Forest plot for hazard ratio of recurrence-free survival; C. Forest plot for hazard ratio of relapse-free survival. HR: hazard ratio.
Venn plots of genes positively or negatively correlated with GCNT3 in lung squamous cell carcinoma. A. The intersection of upregulated DEGs (blue) and genes showed positive correlation with GCNT3 in at least one dataset (red) of lung squamous cell carcinoma. B. The intersection of downregulated DEGs (blue) and genes concurrently showed negative correlation with GCNT3 in at least one datasets (red) of lung squamous cell carcinoma.
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