背景:结直肠癌(CRC)的研究已经发现,在原发肿瘤和转移肿瘤中,PTEN表达持续缺失,强调其在这种疾病中的潜在作用。然而,PTEN对KRAS突变下游蛋白的影响,即p-AKT,p-ERK,和p65(NFkB),仍然未知。本研究旨在探讨PTEN对CRC患者KRAS下游蛋白的抑制作用及其与病理特征的相关性。
方法:从2015年1月1日至2021年12月31日,从杜胡克省的政府和私人实验室收集了86例CRC病例。福尔马林固定,获得石蜡包埋的组织块,这项研究涉及组织病理学分析,PTEN的免疫组织化学,AKT,ERK,和P65标记,和KRAS基因的分子分析。
结果:86例中,有46名男性(53.5%)和40名女性(46.5%),右结肠和左结肠/直肠之间的分布相等。47例肿瘤大于5cm,主要表现为息肉状或溃疡状的生长模式。大多数病例为中分化腺癌,II期和III期分别是最普遍的31例(36%)和34例(39.5%)。发现PTEN之间存在显着关联,ERK表达式,肿瘤位于右半结肠(P=0.031,P=0.009)。肿瘤大小与P65表达相关(P=0.042)。KRAS突变与肿瘤生长类型呈正相关(P=0.035)。肿瘤分级随KRAS突变而增加(P=0.043)。PTEN表达与ERK和AKT标志物显著相关(P分别为0.018和0.035)。P65与KRAS突变相关(P=0.034)。
结论:研究显示PTEN表达与AKT和ERK的抑制有关,以及KRAS基因突变的缺失。相反,PTEN不表达与P65的阳性反应性和KRAS突变的存在。这项研究为PTEN表达之间的复杂相互作用提供了有价值的见解,KRAS突变,和CRC的下游信号通路。它提出了在CRC治疗背景下进一步研究和治疗策略的潜在途径。
BACKGROUND: Colorectal cancer (CRC) research has identified a consistent loss of PTEN expression in both primary tumors and metastasis, highlighting its potential role in this disease. However, the impact of PTEN on downstream proteins of KRAS mutation, namely p-AKT, p-ERK, and p65 (NFkB), remains unknown. This study aims to explore the inhibitory effect of PTEN on KRAS downstream proteins and its correlation with pathological features in CRC patients.
METHODS: From January 1, 2015, to December 31, 2021, 86 CRC cases were collected from governmental and private laboratories in the Duhok province. Formalin-fixed, paraffin-embedded tissue blocks were obtained, and the study involved histopathological analysis, immunohistochemistry of PTEN, AKT, ERK, and P65 markers, and molecular analysis of the KRAS gene.
RESULTS: Among the 86 cases, there were 46 males (53.5%) and 40 females (46.5%), with an equal distribution between right colon and left colon/rectum. Tumors larger than 5cm were observed in 47 cases, predominantly displaying a polypoid or ulcerated growth pattern. Most cases were moderately differentiated adenocarcinomas, with stages II and III being the most prevalent 31 cases (36%) and 34 cases (39.5%) respectively. Significant associations were found between PTEN, ERK expressions, and tumor location in the right colon (P=0.031 and P=0.009 respectively). Tumor size correlated with P65 expression (P=0.042). KRAS mutation showed a positive relationship with the type of tumor growth (P=0.035). Tumor grade increased with KRAS mutations (P=0.043). PTEN expression correlated significantly with ERK and AKT markers (P=0.018 and 0.035 respectively). P65 exhibited an association with KRAS mutation (P=0.034).
CONCLUSIONS: The study revealed PTEN expression in association with the inhibition of AKT and ERK, and the absence of KRAS gene mutation. Conversely, PTEN is not expressed with the positively reactive P65 and the presence of KRAS mutation. This study contributes valuable insights into the complex interplay between PTEN expression, KRAS mutation, and downstream signaling pathways in CRC. It suggests potential avenues for further research and therapeutic strategies in the context of CRC treatment.