Background and objectives: Cytotoxic T-lymphocyte (CTL)-mediated inflammatory response to tumors plays a crucial role in preventing the progression of some cancers. Programmed cell death ligand 1 (PD-L1), a cell-surface glycoprotein, has been reported to repress T-cell-mediated immune responses against tumors. However, the clinical significance of PD-L1 in colorectal cancer (CRC) remains unclear. Our aim was to elucidate the prognostic significance of PD-L1 expression and CD8+ CTL density in CRC. Materials and methods: CD8 and PD-L1 immunostaining was conducted on 157 pathologic specimens from patients with CRC. The CD8+ CTL density and PD-L1 expression within the tumor microenvironment were assessed by immunohistochemistry. Results: Tumor invasion (pT) was significantly correlated with intratumoral (p = 0.011) and peritumoral (p = 0.016) CD8+ CTLs density in the tumor microenvironment. In addition, there was a significant difference in the intensity of CD8+ CTLs between patients with and without distant metastases (intratumoral p = 0.007; peritumoral p = 0.037, T-test). Lymph node metastasis (pN) and TNM stage were significantly correlated with PD-L1 expression in CRC cells (p = 0.015, p = 0.029, respectively). Multivariate analysis revealed a statistically significant relationship between the intratumoral CD8+ CTL density and disease-free survival (DFS) (hazard ratio [HR] 2.06; 95% confidence interval [CI]: 1.01–4.23; p = 0.043). The DFS was considerably shorter in patients with a high expression of PD-L1 in cancer cells than those with a low expression (univariate HR 2.55; 95% CI 1.50–4.34; p = 0.001; multivariate HR 0.48; 95% CI 0.28–0.82; p = 0.007). Conversely, patients with high PD-L1 expression in tumor-infiltrating lymphocytes had a longer DFS in both univariate analysis (HR 0.25; 95% CI: 0.14–0.44; p < 0.001) and multivariate analysis (HR 3.42; 95% CI: 1.95–6.01; p < 0.001). Conclusion: The CD8+ CTL density and PD-L1 expression are prognostic biomarkers for the survival of patients with CRC.
Gastric cancer is one of the foremost causes of cancer related death around the world. The P2X7 receptor (P2X7R), a member of the P2X receptor subfamily of P2 receptors, is a unique molecule that has been shown to affect tumor growth and progression as well as various inflammatory processes, including proliferation of T lymphocytes, release of cytokines, and production of free oxygen radicals. P2X7R has been established as a prognostic parameter in some cancers and, recently, it has been investigated in the development of new targeted therapies. In the present study, we aimed to investigate the prognostic value of P2X7R expression in GC. The expression profile of P2X7R was evaluated immunohistochemically in 156 paraffin-embedded human gastric cancer specimens. P2X7R expression was higher in patients with lymph node metastasis than in those without (p < 0.001). P2X7R overexpression was closely related with tumor-infiltrating lymphocytes [TILs] (p = 0.001), vascular invasion (p = 0.006), depth of invasion (p < 0.001), distant metastasis (p < 0.001), and advanced TNM stage (p < 0.001). Moreover, univariate (HR 3.98; 95% CI 1.89–11.82; p < 0.001) and multivariate (HR 2.24; 95% CI 3.53–12.50; p < 0.001) Cox regression analysis showed that upregulated P2X7R expression clearly correlated with worsened overall survival. In summary, our data revealed that P2X7R may serve as a reliable prognostic parameter and promising therapeutic target for gastric cancer.
Objective: Since colorectal cancers (CRC) are tumors with heterogeneous biological behavior, prediction of their prognosis remains challenging. Caudal-related homeobox gene 2 (CDX2), which has important roles in the development and maintenance of intestines, is thought to have tumor suppressing effect on CRCs. The aim of this study was to investigate the prognostic significance of decreased-CDX2 expression. Method: This retrospective study included 224 patients diagnosed with CRC between 2009 and 2014. Paraffinized blocks of these patients were stained with CDX2 immunohistochemically and evaluated semiquantitatively. Results: Only 35 (15.6%) of 224 patients had low-CDX2 expression. Decrease in CDX2 expression was closely associated with classical prognostic parameters such as histopathologic type, histologic grade, lymph node metastasis, distant metastasis, and TNM stage. Patients with decreased-CDX2 expression had more lymph node metastasis (p=0.013) and advanced TNM stage (p=0.004) than those without decreased-expression. The mean survival was 53.0±0.89 months. Cox regression analysis showed that decreased-CDX2 expression was significantly related with overall survival (Univariate analysis; hazard ratio: 0.
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