MicroRNA 195, lactate dehydrogenase 5, phosphatase and tensin homologue in colorectal cancer: Clinicopathology and prognosis

Abstract

Background: 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.

Aim: 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.

Methods: 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 via immunohistochemistry. Differences in molecular expression between tumor and adjacent normal tissues were compared, along with their correlations with clinicopathological parameters and prognosis.

Results: 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% vs 94.34%, P < 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 (P < 0.05). In CRC tissues, miR195 showed a negative correlation with LDH-5 (r = -0.883, P = 0.015) but a positive correlation with PTEN (r = 0.429, P = 0.006). LDH-5 was negatively associated with PTEN (r = -0.396, P < 0.001). Patients with miR195 positivity, LDH-5 negativity, and PTEN positivity demonstrated significantly better prognosis (P < 0.05).

Conclusion: 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.

Keywords: Clinicopathology; Colorectal cancer; Lactate dehydrogenase-5; MicroRNA 195; Phosphatase and tensin homologue; Prognosis.

Figure 1

Correlation of microRNA 195, lactate dehydrogenase-5, and phosphatase and tensin homologue with patient prognosis. A: MicroRNA 195; B: Phosphatase and tensin homologue; C: Lactate dehydrogenase-5. miR195: MicroRNA 195; PTEN: Phosphatase and tensin homologue; LDH-5: Lactate dehydrogenase-5; TTP: The median time to progression.