PSCA is a critical biomarker for predicting the prognosis of KRAS/TP53 mutant pancreatic cancer patients

M. Gong, Bo Zhang, Xueni Wang, Zeen Zhu, Wei Li, Liang Han, Zheng Wu, Qingyong Ma, Zheng Wang, Weikun Qian
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Abstract

Partly due to the limited effect of chemotherapy or other therapeutic strategies, which may due to the insufficient known of the tumor promotion markers and targets, pancreatic cancer (PC) holds the position of one of the most malignant tumors. This study aims to found a diagnosis/therapeutic molecule that can predicted the prognosis in pancreatic cancer with different gene background. TCGA PAAD based single nucleotide polymorphisms and gene expression data was used to find the different expression genes (DEGs) between KRAS/TP53 mutant samples and no gene mutation samples. GSEA based KEGG analysis and R based GO or immune cell invasion assay were used to explore above DEGs involved pathways. The single center pancreatic cancer cohort accompanied with next generation sequence testing was used to verified the TGCA PAAD based bioinformatic results. Firstly, we found pancreatic cancer patients harbored KRAS and/or TP53 gene mutation have a poor overall survival. Besides, the enrichment analysis showed that mutant KRAS/TP53 was correlated with pancreatic cancer tumor-promotion-related pathways and immune microenvironment. Next, we detected that prostate stem cell antigen (PSCA) was one of the most differential genes in KRAS/TP53 mutant pancreatic cancer tissues. Indeed, the bioinformatic analysis and our clinical data showed PSCA was a biomarker of poor prognosis in pancreatic cancer. PSCA is a critical biomarker for predicting the prognosis of KRAS/TP53 mutant pancreatic cancer patients.
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PSCA 是预测 KRAS/TP53 突变胰腺癌患者预后的关键生物标记物
胰腺癌(PC)是恶性程度最高的肿瘤之一,部分原因是化疗或其他治疗策略的效果有限,也可能是由于对肿瘤促进标志物和靶点的认识不足。本研究旨在找到一种能预测不同基因背景胰腺癌预后的诊断/治疗分子。 研究采用基于 TCGA PAAD 的单核苷酸多态性和基因表达数据,以发现 KRAS/TP53 突变样本与无基因突变样本之间的不同表达基因(DEGs)。基于GSEA的KEGG分析和基于R的GO或免疫细胞侵袭检测用于探索上述DEGs所涉及的通路。为了验证基于 TGCA PAAD 的生物信息学结果,我们使用了单中心胰腺癌队列和新一代序列检测。 首先,我们发现携带 KRAS 和/或 TP53 基因突变的胰腺癌患者总生存率较低。此外,富集分析表明,突变的 KRAS/TP53 与胰腺癌肿瘤促进相关通路和免疫微环境相关。接着,我们发现前列腺干细胞抗原(PSCA)是KRAS/TP53突变胰腺癌组织中差异最大的基因之一。事实上,生物信息学分析和我们的临床数据表明,PSCA是胰腺癌预后不良的生物标志物。 PSCA是预测KRAS/TP53突变胰腺癌患者预后的关键生物标志物。
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