SFRP4 (Secreted frizzled-related protein 4)

We show that tumors in SFRP4 ko mice have less desmoplasia, less epithelial dedifferentiation, reduced growth rate, and reduced progression to metastasis. We conclude that SFRP4 promotes cancer progression in pancreatic cancer and is a promising therapeutic target.

Furthermore, miR-203a expression upon micropeptide treatment resulted in the increased levels of E-cad and decreased levels of N-cad, Snail and Twist, indicating reversal of EMT along with the significant reduction in migratory potential of ovarian CSCs. Our findings for the first time indicated the possible role of miR-203a in regulating autophagy in ovarian CSCs, and reactivation of miR-203a by SFRP4 micropeptides was sufficient to halt the autophagic machinery in ovarian CSCs.

RNF43 is a CRC predisposition gene, but risks are moderate, the reported polyposis phenotype is often absent and molecular phenocopies can occur. N-terminal germline RNF43 variants confer higher risk, although weak effects of C-terminal variants cannot be excluded. Genetic testing and patient management should incorporate these factors.

The obtained results indicate that the lack of MCPIP1 RNase activity activates genes and processes associated with the migratory activity of cancer cells. In summary, the results obtained in this doctoral thesis indicated that MCPIP1 may regulate the progression of clear cell renal cancer at various levels of proangiogenic and prometastatic factors, as well as by influencing the EMT process.

Drug prediction and molecular docking identified chlorendic acid, idarubicin, PHA-848,125, and tosedostat as potential activators of the OAS family due to their strong binding affinity. Conversely, GW842166, NSC 23,766, and metolazone showed high binding affinity for OASL and may inhibit its expression. In summary, The OAS gene family, associated with poor prognosis in gastric cancer, promotes tumour progression and represents a promising therapeutic target.

Our risk prediction model significantly improves the evaluation of prognosis and the prediction of immunotherapy responsiveness in bladder cancer patients. This advancement promotes the development of precise, individualized treatment strategies for bladder cancer.

MMP13+ myofibroblastic cancer-associated fibroblasts were associated with poorly differentiated infiltration patterns, whereas COL11A1+ myofibroblastic cancer-associated fibroblasts were associated with lymph node metastasis. These results suggest that future treatments targeting these cancer-associated fibroblasts and patient stratification based on these cancer-associated fibroblasts are warranted.

These findings reveal the SFRP4-Wnt axis as a central target for PHS, offering novel insights into its molecular action and highlighting its potential as a therapeutic strategy derived from traditional medicine, with clinical implications for targeting Wnt-driven gastric carcinogenesis.

In conclusion, our in-silico findings could facilitate the discovery of potential therapeutic agents against breast cancer. Silibinin and Isotretinoin impede cancer cell development in vitro; nonetheless, this study demonstrated that they directly upregulate sFRP4 and induce apoptosis in breast cancer cells.

In conclusion, sFRP4 exerts dual roles in tumorigenesis, acting either as a tumor suppressor or promoter depending on tissue type, tumor microenvironment, and regulatory mechanisms. This complexity underscores both the challenges and opportunities of targeting sFRP4 in oncology, and future therapeutic strategies incorporating recombinant proteins, synthetic peptides, and nanoparticle-based delivery systems hold promise for harnessing its anti-tumor potential while overcoming resistance mechanisms.

A high mRNA expression level of AZGP1 was associated with longer disease-free survival, whereas high mRNA expressions of ASPN, COMP, RYR2, and SFRP4 were associated with shorter disease-free survival. Prostate cancer patients with genomic alterations associated with PNI may face a higher risk of disease progression after prostatectomy, highlighting the need for further prospective studies to validate these findings.