State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China.
Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China.
Cancer Commun (Lond). 2020 Aug;40(8):355-369. doi: 10.1002/cac2.12069. Epub 2020 Jul 1.
Hepatocellular carcinoma (HCC) is a major health problem and a primary cause of cancer-related death worldwide. Although great advances have achieved recently by large-scale high-throughput analysis, the precise molecular mechanism underlying HCC progression remains to be clearly elucidated. We investigated the relationship between Tescalcin (TESC), a candidate oncogene, and clinicopathological features of HCC patients and explored the role of TECS in HCC development.
To identify new genes involved in HCC development, we analyzed The Cancer Genome Atlas liver cancer database, and TESC was selected for further investigation. HCC tissue microarray analysis for TESC and its association with clinicopathological features were performed to investigate its clinical significance. TESC was knocked down by using short-hairpin RNAs. Cell proliferation was analyzed by WST-1 assay and cell counting. Cell apoptosis was tested by fluorescence-activated cell sorting. A subcutaneous xenograft tumor model in nude mice was established to determine the in vivo function of TESC. Affymetrix microarray was used to identify its molecular mechanism.
TESC was significantly increased in HCC tissues compared with the adjacent normal liver tissues. High expression of TESC was detected in 61 of 172 HCC patients by tissue microarray. Large tumor (> 5 cm) and elevated total bilirubin were associated with high TESC expression (both P < 0.050). In multivariate analysis, TESC was identified as an independent prognostic factor for short overall survival of HCC patients. TESC knockdown impaired HCC cell growth in vitro and in vivo. TESC knockdown significantly increased cell apoptosis in HCC cell lines. Furthermore, Affymetrix microarray analysis revealed that TESC knockdown inhibited tumor proliferation-related pathways while activated cell death-related pathways.
TESC was identified as an independent prognostic factor for short overall survival of HCC patients, and was critical for HCC cell proliferation and survival.
肝细胞癌(HCC)是一个主要的健康问题,也是全球癌症相关死亡的主要原因。尽管最近通过大规模高通量分析取得了重大进展,但 HCC 进展的确切分子机制仍需阐明。我们研究了候选癌基因 Tescalcin(TESC)与 HCC 患者临床病理特征之间的关系,并探讨了 TESC 在 HCC 发展中的作用。
为了鉴定参与 HCC 发展的新基因,我们分析了癌症基因组图谱(TCGA)肝癌数据库,选择 TESC 进行进一步研究。通过 HCC 组织微阵列分析 TESC 及其与临床病理特征的关系,以研究其临床意义。使用短发夹 RNA(shRNA)敲低 TESC。通过 WST-1 检测和细胞计数分析细胞增殖。通过流式细胞术检测细胞凋亡。建立裸鼠皮下移植瘤模型,以确定 TESC 的体内功能。使用 Affymetrix 微阵列鉴定其分子机制。
与相邻正常肝组织相比,TESC 在 HCC 组织中显著增加。通过组织微阵列检测到 172 例 HCC 患者中有 61 例 TESC 高表达。大肿瘤(>5cm)和总胆红素升高与 TESC 高表达相关(均 P<0.050)。多因素分析表明,TESC 是 HCC 患者总体生存时间短的独立预后因素。TESC 敲低在体外和体内均损害 HCC 细胞生长。TESC 敲低显著增加 HCC 细胞系中的细胞凋亡。此外,Affymetrix 微阵列分析显示,TESC 敲低抑制肿瘤增殖相关途径,同时激活细胞死亡相关途径。
TESC 被鉴定为 HCC 患者总体生存时间短的独立预后因素,对 HCC 细胞增殖和存活至关重要。