Prognostic association of starvation-induced gene expression in head and neck cancer

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.

Suppression of head and neck cancer cell survival and cisplatin resistance by GRP78 small molecule inhibitor YUM70

“…First, our independent analysis of the transcript expression levels of GRP78 in HNSCC, based on general as well as specific cancer subtypes, showed that GRP78 transcripts is uniformly elevated in the primary HNSCC tumors compared to normal tissues and that high transcript level of GRP78 is associated with poor prognosis. Our results validate previous studies that clinically, high GRP78 expression, at both protein and mRNA levels, is associated with worse patient survival ( 39 – 41 ). Utilizing two independent siRNAs targeting different regions of human GRP78 , we established that knockdown of GRP78 led to dramatic induction of CHOP, a UPR apoptotic marker in HNSCC, thus GRP78 integrity is a critical anti-apoptotic protein in HNSCC.…”

Transcriptomic analysis of Porphyromonas gingivalis‐infected head and neck cancer cells: Identification of PLAU as a candidate prognostic biomarker

“…A GO analysis, KEGG pathway enrichment analysis, and construction of a PPI network have been used to identify key genes and pathways involved in carcinogenesis and cancer progression. 23,34 Geng et al reported that L6, STAT1, LYN, BDNF, C3,CD274, PDCD1LG2 and CXCL10 were important candidates associated with OSCC using bioinformatical analyses and attempted to demonstrate that P. gingivalis infection promoted the initiation and progression of OSCC. 35 In the present study, the GO analysis extracted 16 biological processes, including the ERK1/2 cascade, response to lipopolysaccharide, regulation of cell proliferation, and negative regulation of cell migration.…”

“…Expression levels higher than the median were classified as the high expression group and the remainder as the low expression group. 23,28,29 The generalized Wilcoxon test and Log rank test were performed to assess the differences in survival times identified by the Kaplan-Meier method (Figures 3 and 4). Among the 12 up-regulated genes, the high expression of CCL20 (Figure 3A), HBEGF (Figure 3E), and PLAU (Figure 3I) correlated with shorter survival times, whereas the high expression of CTGF (Figure 3B), DUSP10 (Figure 3C), EGR3 (Figure 3D), IL1B (Figure 3F), IL24 (Figure 3G), JUN (Figure 3H), PTGS2 (Figure 3J), SEMA7A (Figure 3K) and SGK1 (Figure 3L) did not.…”

“…[18][19][20][21][22] The potential of starvation-induced genes (SIGs), such as CALR, HSPA5 and TRIB3, as molecular prognostic markers has been proposed using the TCGA database of HNSCC patients. 23 Gene expression in HNSCC due to P. gingivalis infection and how changes in gene expression affect the prognosis of HNSCC patients are not clarified. Further efforts are needed to optimize the use of information in the TCGA-HNSCC database.…”

Cordycepin attenuates migration and invasion of HSC-4 oral squamous carcinoma cells through autophagy-dependent FAK/Akt and MMP2/MMP9 suppression

“… 30 Like several cell models, in OSCC, using serum or nutrient starvation results in induction of autophagy. 30 , 31 Autophagy occurs in numerous stressful conditions, such as the presence of damaged proteins and organelles, nutrient deprivation and is a common phenomenon after cancer treatment. 9 , 10 Autophagy plays a paradoxical role in the promotion and suppression of tumours.…”