Tang Zuo, Wen Li-Ming
Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China.
Department of Gastroenterology, Mianyang 404 Hospital, Mianyang 621000, Sichuan Province, China.
World J Gastrointest Surg. 2025 Jul 27;17(7):107121. doi: 10.4240/wjgs.v17.i7.107121.
Colorectal cancer (CRC) is a prevalent gastrointestinal malignancy, with its pathogenesis involving dysregulation of multiple genes, including adenomatous polyposis coli and p53. Emerging evidence suggests that microRNA 195 (miR195) plays a critical role in carcinogenesis by modulating the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway through phosphatase and tensin homologue (PTEN), thereby influencing cellular metabolism. Loss of PTEN function leads to hyperactivation of PI3K/AKT signaling pathway, resulting in upregulated expression of lactate dehydrogenase-5 (LDH-5) and promoting the tumor progression.
To explore the clinical relevance of miR195, LDH-5, and PTEN expression patterns in CRC patient tissues and their association with clinicopathological features and prognosis.
We enrolled 53 CRC patients who received surgical resection at our hospital from January 2020 to February 2022. Fresh tumor tissues and paired adjacent normal tissues (> 5 cm from the tumor margin) were collected. The mRNA expression of miR195 was quantified by real-time quantitative polymerase chain reaction, while the protein expression of LDH-5 and PTEN were assessed immunohistochemistry. Differences in molecular expression between tumor and adjacent normal tissues were compared, along with their correlations with clinicopathological parameters and prognosis.
The positive rate of miR195 in CRC tissues (35.85%) was significantly lower than that in adjacent normal tissues (90.57%). LDH-5 displayed a higher positive rate (79.25%) in the tissues compared to normal tissues (11.32%), while PTEN expression was markedly reduced in tumors (28.30% 94.34%, < 0.05). Elevated expression of miR195 was observed in CRC tissues from patients with earlier tumor, node, metastasis (TNM) stages and without lymph node metastasis. Conversely, higher expression of LDH-5 was associated with advanced TNM stages, lower differentiation grades, and the presence of lymph node metastasis. Additionally, PTEN expression was higher in patients with smaller tumor diameters and no lymph node metastasis ( < 0.05). In CRC tissues, miR195 showed a negative correlation with LDH-5 ( = -0.883, = 0.015) but a positive correlation with PTEN ( = 0.429, = 0.006). LDH-5 was negatively associated with PTEN ( = -0.396, < 0.001). Patients with miR195 positivity, LDH-5 negativity, and PTEN positivity demonstrated significantly better prognosis ( < 0.05).
Low miR195 and PTEN expression, coupled high LDH-5 expression could constitutes a hallmark molecular signature of CRC progression. These signature may act as potential markers for diagnosis and disease assessment, and prognostic evaluation in CRC patients, eventually improving CRC management.
结直肠癌（CRC）是一种常见的胃肠道恶性肿瘤，其发病机制涉及多个基因的失调，包括腺瘤性息肉病基因和p53。新出现的证据表明，微小RNA 195（miR195）通过磷酸酶和张力蛋白同源物（PTEN）调节磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）信号通路，从而在致癌过程中发挥关键作用，进而影响细胞代谢。PTEN功能丧失导致PI3K/AKT信号通路过度激活，导致乳酸脱氢酶-5（LDH-5）表达上调并促进肿瘤进展。
探讨miR195、LDH-5和PTEN在CRC患者组织中的表达模式及其与临床病理特征和预后的关系。
我们纳入了2020年1月至2022年2月在我院接受手术切除的53例CRC患者。收集新鲜肿瘤组织和配对的相邻正常组织（距肿瘤边缘>5 cm）。通过实时定量聚合酶链反应定量miR195的mRNA表达，同时采用免疫组织化学法评估LDH-5和PTEN的蛋白表达。比较肿瘤组织与相邻正常组织之间分子表达的差异，以及它们与临床病理参数和预后的相关性。
CRC组织中miR195的阳性率（35.85%）显著低于相邻正常组织（90.57%）。与正常组织（11.32%）相比，LDH-5在组织中的阳性率更高（79.25%），而肿瘤组织中PTEN的表达明显降低（分别为28.30%和94.34%，P<0.05）。在肿瘤、淋巴结、转移（TNM）分期较早且无淋巴结转移的CRC患者组织中观察到miR195表达升高。相反，LDH-5的高表达与晚期TNM分期、低分化程度和淋巴结转移的存在相关。此外，肿瘤直径较小且无淋巴结转移的患者PTEN表达较高（P<0.05）。在CRC组织中，miR195与LDH-5呈负相关（r=-0.883，P=0.确定015），但与PTEN呈正相关（r=0.429，P=0.006）。LDH-5与PTEN呈负相关（r=-0.396，P<0.001）。miR195阳性、LDH-5阴性和PTEN阳性的患者预后明显较好（P<0.05）。
低miR195和PTEN表达，以及高LDH-5表达可能构成CRC进展的标志性分子特征。这些特征可能作为CRC患者诊断、疾病评估和预后评估的潜在标志物，最终改善CRC的管理。
