Prognostic association of starvation-induced genes in head and neck cancer
Prognostic association of starvation-induced genes in head and neck cancer
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DOI：
10.21203/rs.3.rs-420651/v1
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发表时间：
2021-04
期刊：
影响因子：
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通讯作者：
Masakazu Hamada;Hiroaki Inaba;Kyoko Nishiyama;Sho Yoshida;Yura Yoshiaki;M. Matsumoto-Nakano;N. Uz
中科院分区：
文献类型：
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作者：
Masakazu Hamada;Hiroaki Inaba;Kyoko Nishiyama;Sho Yoshida;Yura Yoshiaki;M. Matsumoto-Nakano;N. Uz
自噬相关基因（ARG）与恶性肿瘤促进的起始和进展有关。为了研究包括 ARG 在内的基因表达动态，将头颈鳞状细胞癌 (HNSCC) 细胞置于无血清条件下以诱导生长迟缓和自噬，并对这些饥饿的细胞进行转录组分析。在位于自噬、细胞增殖和生存信号通路的 21 个饥饿诱导基因 (SIG) 中，我们发现了表现出显着上调或下调的 SIG。其中包括 AGR2、BST2、CALR、CD22、DDIT3、FOXA2、HSPA5、PIWIL4、PYCR1、SGK3 和 TRIB3。利用HNSCC患者的癌症基因组图谱（TCGA）数据库检查上调基因的表达情况，CALR、HSPA5和TRIB3在癌症中相对于实体正常组织高表达，并且发现高表达患者的生存率降低。蛋白质-蛋白质相互作用分析证明了这些基因形成了密集的网络。 Cox回归分析显示CALR、HSPA5和TRIB3的高表达与TCGA-HNSCC患者的不良预后相关。因此，这些在血清饥饿下上调的 SIG 可能是 HNSCC 患者的分子预后标志物。
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. 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 highly expressed relative to solid normal tissue in cancer and the survival rate was found to be 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.