Department of Pathology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, 030013, Shanxi, People's Republic of China.
School of Basic Medicine, Shanxi Medical University, Taiyuan, 030001, Shanxi, People's Republic of China.
J Cancer Res Clin Oncol. 2024 Jan 29;150(2):47. doi: 10.1007/s00432-023-05592-3.
This study aims to investigate the expression patterns and clinical significance of miR-140-3p and homeobox A9 (HOXA9) in colorectal cancer (CRC) selected by bioinformatic study, while elucidating their potential interplay.
The microRNA expression profiles of paired colorectal cancer and matched normal tissues were retrieved from the Gene Expression Omnibus Database. Differentially expressed microRNAs and microRNA candidates were filtered and subjected to further analysis. Clinicopathological data, along with paraffin-embedded samples of colorectal tumor tissues were collected to facilitate comprehensive analysis. Expression levels of miR-140-3p and HOXA9 were quantified using qRT-PCR and immunohistochemistry. Survival rates were determined using the Kaplan-Meier method, and the COX regression model was utilized to identify independent prognostic factors that impact the overall prognosis.
MiR-140-3p was significantly downregulated in colorectal tumors compared to normal tissue, and HOXA9 was identified as a previously unreported potential downstream target. HOXA9 expression was elevated in tumors compared to normal tissues. Reduced miR-140-3p expression was associated with lymph node metastasis, while high HOXA9 expression correlated with both lymph node metastasis and lympho-vascular invasion. Patients with low miR-140-3p and high HOXA9 expression had a poorer prognosis. HOXA9 was identified as an independent risk factor for CRC patient survival.
The miR-140-3p-HOXA9 signaling disruption is closely linked to lymph node metastasis and unfavorable prognosis in CRC. This axis shows promise as a clinical biomarker for predicting the CRC patient survival and a potential therapeutic target.
本研究旨在通过生物信息学研究选择的结肠癌(CRC)中 miR-140-3p 和同源盒 A9(HOXA9)的表达模式和临床意义,同时阐明它们潜在的相互作用。
从基因表达综合数据库中检索了配对的结直肠癌和匹配的正常组织的 microRNA 表达谱。筛选差异表达的 microRNA 和 microRNA 候选物,并进行进一步分析。收集临床病理数据以及结直肠肿瘤组织的石蜡包埋样本,以进行综合分析。使用 qRT-PCR 和免疫组织化学定量检测 miR-140-3p 和 HOXA9 的表达水平。使用 Kaplan-Meier 方法确定生存率,并使用 COX 回归模型确定影响总体预后的独立预后因素。
与正常组织相比,miR-140-3p 在结直肠肿瘤中显著下调,HOXA9 被鉴定为以前未报道的潜在下游靶标。与正常组织相比,肿瘤中 HOXA9 的表达升高。miR-140-3p 表达降低与淋巴结转移有关,而 HOXA9 表达升高与淋巴结转移和淋巴管侵犯均相关。miR-140-3p 低表达和 HOXA9 高表达的患者预后较差。HOXA9 被鉴定为 CRC 患者生存的独立危险因素。
miR-140-3p-HOXA9 信号通路的破坏与 CRC 中的淋巴结转移和不良预后密切相关。该轴有望成为预测 CRC 患者生存的临床生物标志物和潜在的治疗靶点。