与高代谢肿瘤体积相关的差异表达基因可作为胰腺癌的诊断标志物和潜在治疗靶点。
Differentially expressed genes associated with high metabolic tumor volume served as diagnostic markers and potential therapeutic targets for pancreatic cancer.
机构信息
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea.
出版信息
J Transl Med. 2024 May 13;22(1):453. doi: 10.1186/s12967-024-05181-z.
BACKGROUND
The lack of distinct biomarkers for pancreatic cancer is a major cause of early-stage detection difficulty. The pancreatic cancer patient group with high metabolic tumor volume (MTV), one of the values measured from positron emission tomography-a confirmatory method and standard care for pancreatic cancer, showed a poorer prognosis than those with low MTV. Therefore, MTV-associated differentially expressed genes (DEGs) may be candidates for distinctive markers for pancreatic cancer. This study aimed to evaluate the possibility of MTV-related DEGs as markers or therapeutic targets for pancreatic cancer.
METHODS
Tumor tissues and their normal counterparts were obtained from patients undergoing preoperative 18F-FDG PET/CT. The tissues were classified into MTV-low and MTV-high groups (7 for each) based on the MTV2.5 value of 4.5 (MTV-low: MTV2.5 < 4.5, MTV-high: MTV2.5 ≥ 4.5). Gene expression fold change was first calculated in cancer tissue compared to its normal counter and then compared between low and high MTV groups to obtain significant DEGs. To assess the suitability of the DEGs for clinical application, the correlation of the DEGs with tumor grades and clinical outcomes was analyzed in TCGA-PAAD, a large dataset without MTV information.
RESULTS
Total RNA-sequencing (MTV RNA-Seq) revealed that 44 genes were upregulated and 56 were downregulated in the high MTV group. We selected the 29 genes matching MTV RNA-seq patterns in the TCGA-PAAD dataset, a large clinical dataset without MTV information, as MTV-associated genes (MAGs). In the analysis with the TCGA dataset, MAGs were significantly associated with patient survival, treatment outcomes, TCGA-PAAD-suggested markers, and CEACAM family proteins. Some MAGs showed an inverse correlation with miRNAs and were confirmed to be differentially expressed between normal and cancerous pancreatic tissues. Overexpression of KIF11 and RCC1 and underexpression of ADCY1 and SDK1 were detected in ~ 60% of grade 2 pancreatic cancer patients and associated with ~ 60% mortality in stages I and II.
CONCLUSIONS
MAGs may serve as diagnostic markers and miRNA therapeutic targets for pancreatic cancer. Among the MAGs, KIF11, RCC1, ADCY, and SDK1 may be early diagnostic markers.
背景
缺乏用于胰腺癌早期检测的特异性生物标志物是导致这一问题的主要原因。在接受正电子发射断层扫描（一种用于胰腺癌的确认方法和标准护理）的胰腺癌患者中，代谢肿瘤体积（MTV）较高的患者比 MTV 较低的患者预后更差。因此，与 MTV 相关的差异表达基因（DEG）可能是胰腺癌的独特标志物候选者。本研究旨在评估 MTV 相关 DEG 作为胰腺癌标志物或治疗靶点的可能性。
方法
从接受术前 18F-FDG PET/CT 的患者中获得肿瘤组织及其相应的正常组织。根据 MTV2.5 值为 4.5（MTV-低：MTV2.5<4.5，MTV-高：MTV2.5≥4.5），将组织分为 MTV-低和 MTV-高组（每组 7 例）。首先计算癌症组织与正常组织相比的基因表达倍数变化，然后比较 MTV 低和 MTV 高组之间的差异表达基因。为了评估 DEG 用于临床应用的适宜性，在没有 MTV 信息的大型数据集 TCGA-PAAD 中，分析了 DEG 与肿瘤分级和临床结局的相关性。
结果
总 RNA 测序（MTV RNA-Seq）显示，在 MTV 高组中，有 44 个基因上调，56 个基因下调。我们选择了与 TCGA-PAAD 数据集（一个没有 MTV 信息的大型临床数据集）中 MTV RNA-Seq 模式相匹配的 29 个基因作为与 MTV 相关的基因（MAGs）。在 TCGA 数据集的分析中，MAGs 与患者生存、治疗结局、TCGA-PAAD 提示标志物和 CEACAM 家族蛋白显著相关。一些 MAGs 与 miRNA 呈负相关，并在正常和癌变胰腺组织之间证实存在差异表达。在约 60%的 2 级胰腺癌患者中检测到 KIF11 和 RCC1 的过表达以及 ADCY1 和 SDK1 的低表达，并且在 I 期和 II 期与约 60%的死亡率相关。
结论
MAGs 可能作为胰腺癌的诊断标志物和 miRNA 治疗靶点。在 MAGs 中，KIF11、RCC1、ADCY 和 SDK1 可能是早期诊断标志物。
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