Abstract
Autophagy-related genes (ARGs) have been implicated in the initiation and progression of malignant tumor promotion. To investigate the dynamics of expression of genes, including ARGs, head and neck squamous cell carcinoma (HNSCC) cells were placed under serum-free conditions to induce growth retardation and autophagy, and these starved cells were subjected to transcriptome analysis. Among the 21 starvation-induced genes (SIGs) located in the autophagy, cell proliferation, and survival signaling pathways, we identified SIGs that showed prominent up-regulation or down-regulation in vitro. These included AGR2, BST2, CALR, CD22, DDIT3, FOXA2, HSPA5, PIWIL4, PYCR1, SGK3, and TRIB3. The Cancer Genome Atlas (TCGA) database of HNSCC patients was used to examine the expression of up-regulated genes, and CALR, HSPA5, and TRIB3 were found to be highly expressed relative to solid normal tissue in cancer and the survival rate was reduced in patients with high expression. Protein–protein interaction analysis demonstrated the formation of a dense network of these genes. Cox regression analysis revealed that high expression of CALR, HSPA5, and TRIB3 was associated with poor prognosis in patients with TCGA-HNSCC. Therefore, these SIGs up-regulated under serum starvation may be molecular prognostic markers in HNSCC patients.
Highlights
Autophagy-related genes (ARGs) have been implicated in the initiation and progression of malignant tumor promotion
SAS cells proliferation and migration were considerably diminished, while cell morphology did not change (Fig. 1A–D). These findings were consistent with Ca9-22 cells proliferation, migration, and morphology mediated by serum starvation (Fig. S1A-D), and suggest that there is no much of differences between head and neck squamous cell carcinoma (HNSCC) cell lines
In cells cultured for 24 h in the absence of serum, autophagosomes and/or autolysosomes containing degraded mitochondria and dense structures, characteristic of autophagic cells not present in control cells, were observed (Fig. 1E)
Summary
Autophagy-related genes (ARGs) have been implicated in the initiation and progression of malignant tumor promotion. Among the 21 starvation-induced genes (SIGs) located in the autophagy, cell proliferation, and survival signaling pathways, we identified SIGs that showed prominent up-regulation or down-regulation in vitro These included AGR2, BST2, CALR, CD22, DDIT3, FOXA2, HSPA5, PIWIL4, PYCR1, SGK3, and TRIB3. Cox regression analysis revealed that high expression of CALR, HSPA5, and TRIB3 was associated with poor prognosis in patients with TCGA-HNSCC. These SIGs up-regulated under serum starvation may be molecular prognostic markers in HNSCC patients. Using the TCGA database, many studies on the deviation of genes and signaling pathways involved in carcinogenesis and prognosis are being conducted This includes studies on hypoxia-immune s ignature[18], cancer-associated alternative splicing event-related g enes[19], the miRNA-30 family[20,21,22], and the KEAP1-NRF2-CUL3. More efforts are needed to make better use of the TCGA-HNSCC database
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