[Cellular prion protein expression and its correlation with pathological features in colorectal cancer]

Objective: To investigate the expression of cellular prion protein (PrPc) and tumor stem cell marker, CD44, in colorectal cancer, and to analyze their correlation with the metastasis and prognosis of colorectal cancer. Methods: A retrospective analysis was conducted on 212 colorectal cancer samples received by the Department of Pathology, Beijing Hospital, Beijing, China from August 2017 to February 2024. Immunohistochemical staining and immunofluorescence double staining were used to examine the expression of PrPc and CD44 in colorectal cancer. Their relationship with the clinical outcomes of colorectal cancer was analyzed. The expression of PrPc and CD44 was scored using the proportion of positive tumor cells and staining intensity, and the expression levels were divided into the 4 categories of negative, weakly positive, moderately positive, and strongly positive. The knockout of PrPc in colorectal cancer stem cells P6C was performed to assess cell growth and migration capacity, and to analyze the role of PrPc in tumor metastasis. Results: The study cohort comprised 212 patients, including 130 males and 82 females, with an age range of 33 to 96 years and a mean age of (64.7±12.7) years. According to the tumor-node-metastasis (TNM) staging system, the cases were distributed as follows: 26 cases in stage T1, 61 cases in T2, 58 cases in T3, and 67 cases in T4. Regarding lymph node status, 151 patients were free from lymph node metastasis, while 61 patients had lymph node metastasis. In terms of distant metastasis, 136 patients had no distant metastasis, and 76 patients were diagnosed with distant metastasis. Histopathological grading revealed 1 case of well-differentiated adenocarcinoma, 166 cases of moderately-differentiated adenocarcinoma, and 45 cases of poorly-differentiated adenocarcinoma. The percentage of PrPc-expressing cells in advanced tumors (T4, 88.1%, 59/67), poorly-differentiated tumors (82.2%, 37/45), tumors with lymph node metastasis (86.9%, 53/61) or distant metastasis (85.5%, 65/76) was higher than that in early-stage or well-differentiated tumors. The co-expression of PrPc and CD44 in advanced tumors (86.6%, 58/67), poorly-differentiated tumors (80.0%, 36/45), and tumors with lymph node metastasis (85.3%, 52/61) or distant metastasis (84.2%, 64/76) was also higher. Statistical analysis showed that the expression of PrPc alone and the co-expression of PrPc/CD44 were significantly correlated with tumor differentiation, T staging, lymph node metastasis, and distant metastasis (P<0.05). Western blot analysis showed that PrPc knockout suppressed the expression of N-cadherin and Twist, metastasis-related proteins. Scratch assay and Transwell assay demonstrated that PrPc knockout inhibited the invasion and migration of cancer stem cells. Continuous cell counting revealed that PrPc knockout impaired the proliferation of colorectal cancer stem cells (P<0.01). Conclusions: The expression of PrPc may be related to the occurrence and progression of colorectal cancer. It thus can serve as an indicator of tumor invasion, metastasis and prognosis. The knockout of PrPc inhibits growth and migration of tumor stem cells, revealing that PrPc may have the ability to promote the invasion and metastasis of colorectal cancer.