Background. Programmed cell death receptor 1 (PD-1) and T cell immunoglobulin mucin-3 (Tim-3) are considered as important immunosuppressive molecules and play an important role in tumor immune escape and cancer progression. However, it remains unclear whether PD-1 and Tim-3 are coexpressed in stage I-III colorectal cancer (CRC) and how they impact on the prognosis of the disease. Materials and Methods. A total of two cohorts with 451 patients who underwent surgery for stage I-III CRC treatment were enrolled in the study. Among which, 378 cases were from The Cancer Genome Atlas (TCGA) database and 73 cases were from the Fourth Hospital of Hebei Medical University (FHHMU) cohort. The mRNA expressions of PD-1 and Tim-3 in tumor tissue in stage I-III CRC were obtained from TCGA database. Immunohistochemistry was used to assess the expressions of PD-1 and Tim-3 in tumor tissue in stage I-III CRC in the FHHMU cohort. Interactive relationships between PD-1 and Tim-3 were retrieved through the online STRING database, which was used to study the interactions between proteins. DAVID, consisting of comprehensive biological function annotation information, was applied for the GO and KEGG pathway enrichment analysis of the interactive genes. Results. In the FHHMU cohort, the high expressions of PD-1 and Tim-3 were, respectively, found in 42.47% and 84.93% of stage I-III CRC tissue. PD-1 was significantly associated with age, primary site, and lymphatic metastasis. Tim-3 was closely related to the primary site. Correlation analysis showed that PD-1 and Tim-3 were positively correlated (r=0.5682, P<0.001). In TCGA cohort, PD-1 and Tim-3 were associated with the prognosis of CRC patients in terms of 5-year survival (P<0.05). In the FHHMU cohort, the 5-year survival of patients with high levels of PD-1 and Tim-3 was 54.84% and 65.85%, respectively. Among which, the high expression of PD-1 was associated with poor prognosis (5-year OS: 54.84% vs. 88.10%, P=0.003). The 5-year survival rate of CRC patients with coexpression of PD-1 and Tim-3 was 45.00%, which was significantly worse than non-coexpression (72.73%, 85.71%, and 90.48% separately). The functional network of PD-1 and Tim-3 primarily participates in the regulation of immune cell activation and proliferation, immune cell receptor complex, cell adhesion molecules, and T cell receptor signaling pathway. Conclusion. In summary, upregulation of PD-1 and Tim-3 in stage I-III CRC tumor tissue could be associated with the poor prognosis of patients. Those patients with coexpression of PD-1 and Tim-3 may have a significantly worse prognosis.
The interaction between captopril, an inhibitor of angiotensin converting enzyme and human serum albumin, a principal plasma protein in the liver has been investigated in vitro under a simulated physiological condition by UV-vis spectrophotometry and fluorescence spectrometry. The intrinsic fluorescence intensity of human serum albumin was strongly quenched by captopril. The binding constants and the number of binding sites can be calculated from the data obtained from fluorescence quenching experiments. The negative value of G 0 reveals that the binding process is a spontaneous process. According to the van't Hoff equation, the standard enthalpy change (H 0 ) and standard entropy change (S 0 ) for the reaction were calculated to be 35.98 KJmol -1 and 221.25 Jmol -1 K. It indicated that the hydrophobic interactions play a main role in the binding of captopril to human serum albumin. In addition, the distance between captopril (acceptor) and tryptophan residues of human serum albumin (donor) was estimated to be 1.05 nm according to the Förster's resonance energy transfer theory. The results obtained herein will be of biological significance in pharmacology and clinical medicine.
colorectal cancer (crc) remains one of the most common cancer types worldwide. a few previous studies have examined whether Her4 may promote the progression of crc. The present study examined the associations among the expression levels of members of the Her family, and investigated the potential mechanism underlying the function of Her4 in crc cells. immunohistochemistry analysis was conducted to detect the expression levels of Her family members in patients with crc. Her4 expression was knocked down using short hairpin RNA in HCT116 cells, and confirmed by quantitative Pcr and western blotting. The proliferation and adhesion of crc cells were analyzed by ccK-8 assays and adhesive assays, respectively. Flow cytometry was used to measure cell apoptosis. Western blotting and immunofluorescence staining in CRC cells were performed to identify proteins related to epithelial-mesenchymal transition. The proportion of patients with crc presenting positive expression of the Her family members epidermal growth factor receptor (eGFr), Her2, Her3 and Her4 were 72.1, 45.2, 43.8 and 34.2%, respectively. no relationship was found between Her4 and eGFr, Her2 or Her3 expression. Higher expression of Her4 was positively associated with lymph node metastasis (P=0.039). in the present study, Her4 expression was found to be associated with an unfavorable clinical outcome in patients with crc (P logrank =0.020). cell proliferation was inhibited, and apoptosis was increased following Her4 knockdown. Furthermore, Her4 knockdown increased the expression of e-cadherin and decreased the expressions of n-cadherin and vimentin (P<0.05). Her4 expression was found to be unrelated to other Her family members. in the present study, positive expression of Her4 promoted the progression of crc through epithelial-mesenchymal transition.
Abstract. The present study aimed to evaluate the expression of human epidermal growth factor receptor (HER4) isoforms and their ligand neuregulin 1 (NRG1) isoforms in human primary colorectal cancer (CRC). The mRNA expression of HER4 isoforms JM-a, JM-b, CYT1 and CYT2, and their ligand isoforms NRG1 I, II and III in CRC tissues and adjacent normal tissues were quantified by reverse transcription-quantitative polymerase chain reaction analysis. Univariate analysis and logistic regression analysis were performed to analyze the association between HER4 and NRG1 expression and lymph node metastasis in CRC. The expression levels of CYT1 (P=0.002), CYT2 (P=0.002) and NRG1 type III (P<0.001) were significantly higher in the CRC tissues than in the adjacent normal tissues. The expression of CYT2 was correlated with tumor stage (P=0.018), lymph node status (P=0.015) and tumor-node-metastasis (P=0.038) in CRC. The expression of NRG1III was correlated with lymph node metastasis, and the expression of CYT2 was associated with the expression of NRG1III (r=0.691, P<0.01). The logistic regression analysis indicated that expression of CYT2 >50 was a risk factor for lymph node metastasis in CRC. In conclusion the expression levels of CYT1, CYT2 and NRG1III were upregulated in CRC. An expression of CYT-2 >50 was identified as a risk factor for lymph node metastasis in CRC. Therefore, CY-2 and NRG1III may be involved in the progression of CRC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.