在结直肠癌中调查基因组学、蛋白组学和转录后调控谱的研究：原发肿瘤与相关转移的比较研究。
Investigating genomic, proteomic, and post-transcriptional regulation profiles in colorectal cancer: a comparative study between primary tumors and associated metastases.
发表日期：2023 Sep 05
作者：
Hersh Ham-Karim, Ola Negm, Narmeen Ahmad, Mohammad Ilyas
来源：
GENES & DEVELOPMENT
摘要：
大约50%的原发结肠直肠癌患者会发展成肝转移。本研究探讨了原发结肠癌（pCRC）和相应转移瘤之间可能存在的分子差异。共测试了22对pCRC和转移瘤。使用下一代测序技术对22/22对原发转移肿瘤进行了26个癌相关基因的突变分析，使用qPCR在21/22对中研究了一组6个microRNA (miRNA)的表达，使用逆相蛋白质鞘芯阵列（RPPA）在20/22位患者的肿瘤对中测试了22个蛋白生物标志物。在原发和转移肿瘤中，各基因的突变率如下：TP53(86%)，APC(44 %)，KRAS(36%)，PIK3CA(9%)，SMAD4(9%)，NRAS(9%)，FBXW7、BRAF、GNAS和CDH1的突变率为4%。在60个位点中，54/60 (90%)个位点的原发转移肿瘤突变状态完全相同。然而，在40/58个遗传位点中存在异质性状态的不一致性（z-score = 6.246，差异 = 0.3793，P < 0.0001）。此外，原发和转移肿瘤的miRNA表达状态存在不一致性，57.14-80.95%的原发转移肿瘤对在所有测试的miRNA中显示出了原发转移相对表达的改变。此外，16/20(80%)个肿瘤对在所分析的至少3/6(50%)个蛋白质标志途径中显示出了变化。原发结肠肿瘤的分子改变与其匹配的转移瘤显著不同。这些差异对于患者的预后和治疗反应具有重要影响。
© 2023. BioMed Central Ltd., part of Springer Nature.
Approximately 50% of patients with primary colorectal carcinoma develop liver metastases. This study investigates the possible molecular discrepancies between primary colorectal cancer (pCRC) and their respective metastases.A total of 22 pairs of pCRC and metastases were tested. Mutation profiling of 26 cancer-associated genes was undertaken in 22/22primary-metastasis tumour pairs using next-generation sequencing, whilst the expression of a panel of six microRNAs (miRNAs) was investigated using qPCRin 21/22 pairs and 22 protein biomarkers was tested using Reverse Phase Protein Array (RPPA)in 20/22 patients' tumour pairs.Among the primary and metastatic tumours the mutation rates for the individual genes are as follows:TP53 (86%), APC (44%), KRAS (36%), PIK3CA (9%), SMAD4 (9%), NRAS (9%) and 4% for FBXW7, BRAF, GNAS and CDH1. The primary-metastasis tumour mutation status was identical in 54/60 (90%) loci. However, there was discordance in heterogeneity status in 40/58 genetic loci (z-score = 6.246, difference = 0.3793, P < 0.0001). Furthermore, there was loss of concordance in miRNA expression status between primary and metastatic tumours, and 57.14-80.95% of the primary-metastases tumour pairs showed altered primary-metastasis relative expression in all the miRNAs tested. Moreover, 16 of 20 (80%) tumour pairs showed alteration in at least 3 of 6 (50%) of the protein biomarker pathways analysed.The molecular alterations of primary colorectal tumours differ significantly from those of their matched metastases. These differences have profound implications for patients' prognoses and response to therapy.© 2023. BioMed Central Ltd., part of Springer Nature.