Hamidi Amir Abbas, Forghanifard Mohammad Mahdi, Gholamin Mehran, Moghbeli Meysam, Memar Bahram, Jangjoo Ali, Motie Mohammad Reza, Molaei Fatemeh, Abbaszadegan Mohammad Reza
Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran.
Microb Pathog. 2022 Jan;162:105304. doi: 10.1016/j.micpath.2021.105304. Epub 2021 Nov 21.
Epithelial-mesenchymal transition (EMT) has a fundamental role in tumor initiation, progression, and metastasis. Helicobacter pylori (HP) induces EMT and thus causes gastric cancer (GC) by deregulating multiple signaling pathways involved in EMT. TWIST1 and MAML1 have been confirmed to be critical inducers of EMT via diverse signaling pathways such as Notch signaling. This study aimed to investigate for the first time possible associations between TWIST1/MAML1 mRNA expression levels, HP infection, and clinicopathological characteristics in GC patients.
TWIST1 and MAML1 mRNA expression levels were evaluated in tumoral and adjacent normal tissues in 73 GC patients using the quantitative reverse transcription PCR (RT-qPCR) method. PCR technique was also applied to examine the infection with HP in GC samples.
Upregulation of TWIST1 and MAML1 expression was observed in 35 (48%) and 34 (46.6%) of 73 tumor samples, respectively. Co-overexpression of these genes was found in 26 of 73 (35.6%) tumor samples; meanwhile, there was a significant positive correlation between MAML1 and TWIST1 mRNA expression levels (P < 0.001). MAML1 overexpression exhibited meaningful associations with advanced tumor stages (P = 0.006) and nodal metastases (P ˂ 0.001). 34 of 73 (46.6%) tumors tested positive for HP, and meanwhile, MAML1 expression was positively related with T (P = 0.05) and grade (P = 0.0001) in these HP-positive samples. Increased TWIST1 expression was correlated with patient sex (P = 0.035) and advanced tumor grade (P = 0.017) in HP-infected tumors. Furthermore, TWIST1 and MAML1 expression levels were inversely linked with histologic grade in HP-negative tumor samples (P = 0.021 and P = 0.048, respectively).
We propose TWIST1 and MAML1 as potential biomarkers of advanced-stage GC that determine the characteristics and aggressiveness of the disease. Based on accumulating evidence and our findings, they can be introduced as promising therapeutic targets to modify functional abnormalities in cells that promote GC progression. Moreover, HP may enhance GC growth and metastasis by disrupting TWIS1/MAML1 expression patterns and related pathways.
上皮-间质转化（EMT）在肿瘤的发生、发展和转移中起重要作用。幽门螺杆菌（HP）通过失调EMT相关的多种信号通路诱导EMT，进而引发胃癌（GC）。TWIST1和MAML1已被证实是通过Notch信号等多种信号通路诱导EMT的关键因子。本研究旨在首次探究GC患者中TWIST1/MAML1 mRNA表达水平、HP感染与临床病理特征之间的可能关联。
采用定量逆转录PCR（RT-qPCR）法检测73例GC患者肿瘤组织及癌旁正常组织中TWIST1和MAML1 mRNA的表达水平。同时应用PCR技术检测GC样本中的HP感染情况。
73例肿瘤样本中，分别有35例（48%）和34例（46.6%）观察到TWIST1和MAML1表达上调。73例肿瘤样本中有26例（35.6%）发现这两个基因共过表达；同时，MAML1和TWIST1 mRNA表达水平之间存在显著正相关（P < 0.001）。MAML1过表达与肿瘤晚期（P = 0.006）和淋巴结转移（P < 0.001）显著相关。73例肿瘤中有34例（46.6%）HP检测呈阳性，同时，在这些HP阳性样本中，MAML1表达与T分期（P = 0.05）和肿瘤分级（P = 0.0001）呈正相关。在HP感染的肿瘤中，TWIST1表达增加与患者性别（P = 0.035）和肿瘤高级别（P = 0.017）相关。此外，在HP阴性肿瘤样本中，TWIST1和MAML1表达水平与组织学分级呈负相关（分别为P = 0.021和P = 0.048）。
我们提出TWIST1和MAML1作为晚期GC的潜在生物标志物，它们决定了疾病的特征和侵袭性。基于越来越多的证据和我们的研究结果，它们可作为有前景的治疗靶点，以纠正促进GC进展的细胞功能异常。此外，HP可能通过破坏TWIS1/MAML1表达模式及相关信号通路来促进GC的生长和转移。
