Yang Mingjun, Song Boni, Liu Juxiang, Bing Zhitong, Wang Yonggang, Yu Linmiao
School of Life Science and Engineering, Lanzhou University of Technology, Lanzhou, Gansu, China.
Institute of Modern Physics of Chinese Academy of Sciences, Lanzhou, China.
PeerJ. 2020 Nov 11;8:e10297. doi: 10.7717/peerj.10297. eCollection 2020.
Pancreatic cancer (PC) has much weaker prognosis, which can be divided into diabetes and non-diabetes. PC patients with diabetes mellitus will have more opportunities for physical examination due to diabetes, while pancreatic cancer patients without diabetes tend to have higher risk. Identification of prognostic markers for diabetic and non-diabetic pancreatic cancer can improve the prognosis of patients with both types of pancreatic cancer.
Both types of PC patients perform differently at the clinical and molecular levels. The Cancer Genome Atlas (TCGA) is employed in this study. The gene expression of the PC with diabetes and non-diabetes is used for predicting their prognosis by LASSO (Least Absolute Shrinkage and Selection Operator) Cox regression. Furthermore, the results are validated by exchanging gene biomarker with each other and verified by the independent Gene Expression Omnibus (GEO) and the International Cancer Genome Consortium (ICGC). The prognostic index (PI) is generated by a combination of genetic biomarkers that are used to rank the patient's risk ratio. Survival analysis is applied to test significant difference between high-risk group and low-risk group.
An integrated gene prognostic biomarker consisted by 14 low-risk genes and six high-risk genes in PC with non-diabetes. Meanwhile, and another integrated gene prognostic biomarker consisted by five low-risk genes and three high-risk genes in PC with diabetes. Therefore, the prognostic value of gene biomarker in PC with non-diabetes and diabetes are all greater than clinical traits (HR = 1.102, -value < 0.0001; HR = 1.212, -value < 0.0001). Gene signature in PC with non-diabetes was validated in two independent datasets.
The conclusion of this study indicated that the prognostic value of genetic biomarkers in PCs with non-diabetes and diabetes. The gene signature was validated in two independent databases. Therefore, this study is expected to provide a novel gene biomarker for predicting prognosis of PC with non-diabetes and diabetes and improving clinical decision.
胰腺癌(PC)预后极差,可分为糖尿病相关型和非糖尿病相关型。糖尿病相关的胰腺癌患者因糖尿病会有更多体检机会,而无糖尿病的胰腺癌患者往往风险更高。识别糖尿病和非糖尿病相关胰腺癌的预后标志物可改善这两类胰腺癌患者的预后。
两类胰腺癌患者在临床和分子水平表现各异。本研究采用癌症基因组图谱(TCGA)。通过LASSO(最小绝对收缩和选择算子)Cox回归,利用糖尿病相关和非糖尿病相关胰腺癌的基因表达来预测其预后。此外,通过相互交换基因生物标志物验证结果,并由独立的基因表达综合数据库(GEO)和国际癌症基因组联盟(ICGC)进行核实。预后指数(PI)由遗传生物标志物组合生成,用于对患者的风险比率进行排名。应用生存分析来检验高危组和低危组之间的显著差异。
非糖尿病相关胰腺癌中有一个由14个低风险基因和6个高风险基因组成的综合基因预后生物标志物。同时,糖尿病相关胰腺癌中有另一个由5个低风险基因和3个高风险基因组成的综合基因预后生物标志物。因此,基因生物标志物在非糖尿病相关和糖尿病相关胰腺癌中的预后价值均大于临床特征(HR = 1.102,P值<0.0001;HR = 1.212,P值<0.0001)。非糖尿病相关胰腺癌中的基因特征在两个独立数据集中得到验证。
本研究结果表明基因生物标志物在非糖尿病相关和糖尿病相关胰腺癌中的预后价值。该基因特征在两个独立数据库中得到验证。因此,本研究有望为预测非糖尿病相关和糖尿病相关胰腺癌的预后及改善临床决策提供一种新的基因生物标志物。