Ham-Karim Hersh, Negm Ola, Ahmad Narmeen, Ilyas Mohammad
Department of Pharmacy, College of Medicine, Komar University of Science and Technology, Chaq-Chaq-Qualaraisi, Sulaimani, Iraq.
Division of Medical Sciences and Graduate Entry Medicine, Faculty of Medicine and Health Sciences, School of Medicine, University of Nottingham, Nottingham, UK.
Cancer Cell Int. 2023 Sep 5;23(1):192. doi: 10.1186/s12935-023-03020-7.
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.
约50%的原发性结直肠癌患者会发生肝转移。本研究调查原发性结直肠癌（pCRC）与其各自转移灶之间可能存在的分子差异。
共检测了22对pCRC及其转移灶。使用下一代测序技术对22/22对原发性-转移瘤进行了26个癌症相关基因的突变分析，同时使用qPCR对21/22对样本检测了一组6种微小RNA（miRNA）的表达，并使用反相蛋白质阵列（RPPA）对20/22对患者肿瘤样本检测了22种蛋白质生物标志物。
在原发性和转移性肿瘤中，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为4%。54/60（90%）个位点的原发性-转移瘤突变状态相同。然而，40/58个基因位点的异质性状态存在不一致（z值=6.246，差异=0.3793，P<0.0001）。此外，原发性和转移性肿瘤之间miRNA表达状态缺乏一致性，57.14 - 80.95%的原发性-转移瘤对在所有检测的miRNA中显示出原发性-转移相对表达改变。而且，20对（80%）肿瘤样本中有16对在分析的6种（50%）蛋白质生物标志物途径中至少有3种发生改变。
原发性结直肠癌肿瘤的分子改变与其匹配的转移灶有显著差异。这些差异对患者的预后和治疗反应具有深远影响。
