TY - JOUR
T1 - Prognostic association of starvation-induced gene expression in head and neck cancer
AU - Hamada, Masakazu
AU - Inaba, Hiroaki
AU - Nishiyama, Kyoko
AU - Yoshida, Sho
AU - Yura, Yoshiaki
AU - Matsumoto-Nakano, Michiyo
AU - Uzawa, Narikazu
N1 - Funding Information:
This work was supported in part by a Grant-in Aid for Scientific Research from the Japan Society for the Promotion of Science (No. 18K09787, No.20K09918 and No. 20K18692).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-021-98544-1
DO - 10.1038/s41598-021-98544-1
M3 - Article
C2 - 34580365
AN - SCOPUS:85115765341
SN - 2045-2322
VL - 11
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 19130
ER -
