Hassan Redir T, Al Hassawi Bashar, Alkazzaz Maysoon
Department of Anatomy, University of Duhok, Duhok, IRQ.
Department of Biology, University of Duhok, Duhok, IRQ.
Cureus. 2024 Feb 8;16(2):e53884. doi: 10.7759/cureus.53884. eCollection 2024 Feb.
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.
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.
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).
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.
结直肠癌（CRC）研究已证实原发性肿瘤和转移灶中PTEN表达均持续缺失，突显了其在该疾病中的潜在作用。然而，PTEN对KRAS突变下游蛋白，即p-AKT、p-ERK和p65（NFkB）的影响仍不清楚。本研究旨在探讨PTEN对KRAS下游蛋白的抑制作用及其与CRC患者病理特征的相关性。
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。获取福尔马林固定、石蜡包埋的组织块，该研究包括组织病理学分析、PTEN、AKT、ERK和P65标志物的免疫组织化学以及KRAS基因的分子分析。
86例病例中，男性46例（53.5%），女性40例（46.5%），右半结肠和左半结肠/直肠分布均衡。47例肿瘤大于5cm，主要表现为息肉样或溃疡样生长模式。大多数病例为中度分化腺癌，II期和III期最为常见，分别为31例（36%）和34例（39.5%）。发现PTEN、ERK表达与右半结肠肿瘤位置之间存在显著相关性（分别为P = 0.031和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（分别为P = 0.018和0.035）。P65与KRAS突变有关联（P = 0.034）。
该研究揭示PTEN表达与AKT和ERK的抑制相关，且不存在KRAS基因突变。相反，PTEN与呈阳性反应的P65以及KRAS突变的存在不相关。本研究为CRC中PTEN表达、KRAS突变和下游信号通路之间的复杂相互作用提供了有价值的见解。它为CRC治疗背景下的进一步研究和治疗策略提示了潜在途径。
