TIMP1 overexpression

Our study has discovered a novel prognostic index derived from BM-related genes in CRC patients. Specifically, the new model enables patient stratification, improving the selection of individuals likely to benefit from immunotherapy.

Drug sensitivity analysis, conducted using the DepMap database, revealed that colorectal cancer cell lines exhibiting elevated levels of TIMP1 expression were more responsive to certain drugs, such as CC-90003, Pitavastatin, Atuveciclib, and CT7001, compared to those with low levels of TIMP1. Furthermore, TIMP1 expression was positively correlated with that of ferroptosis-related genes, such as GPX4 and HSPA5. TIMP1 can be used as a biomarker for colorectal cancer and is associated with the immunological microenvironment, drug sensitivity, and ferroptosis inhibition in this disease.

Upon immunohistochemical (IHC) analysis of FFPE blocks however, COL1A2 showed better differential staining between tumor epithelia and tumor stroma. Similar data science driven approach utilizing single cell sequencing and RNAseq data from stabilized CAFs can be employed to identify CAF-markers in various cancers.

This study provides promising insights into predicting glioma prognosis and identifying a potential therapeutic target in TIMP1.

Here, we show that mesenchymal-like TNBC cells express TIMP-1, whose levels are further increased in cells generated to be resistant to cisplatin (Cis-Pt-R) and doxorubicin (Dox-R). Importantly, released TIMP-1 reassociates with plasma membrane by binding to CD63 and, in the absence of CD63 expression, TIMP-1-mediated chemoresistance is blocked. Thus, our results identify TIMP-1 as a new biomarker of TNBC chemoresistance and lay the groundwork for evaluating whether blockade of TIMP-1 signal is a viable treatment strategy.

TIMP1 depletion in CRC cells enhances sorafenib-triggered ferroptosis by reducing PI3K/Akt axis signal transduction. The combination of sorafenib and GPX4 inhibitors such as RSL3 may be a promising therapy against CRC.

We also found that high TIMP1 and CD63 mRNA levels combined define a stronger prognostic biomarker than TIMP1 alone. Our results identify an excessive stromal TIMP-1 within the tumor microenvironment selectively in lung ADC, and implicate it in a novel tumor-promoting TAF-carcinoma crosstalk, thereby pointing to TIMP-1/CD63 interaction as a novel therapeutic target in lung cancer.

Drugs that did not match the drug-likeness rules exhibited lower permeability in the 3D tumor model. Taken together, our findings indicate that this 3D multicellular tumor model may be used as a reliable platform for efficiently screening therapeutics agents for solid tumors.

In addition, we also found that TIMP1 prompted the progression of RCC via epithelial-to-mesenchymal transition (EMT) signaling pathway. In conclusion, the present results suggested that TIMP1 indicated poor prognosis of renal cell carcinoma and could serve as a potential diagnostic and prognostic biomarker for RCC.

TIMP-1 and CD34CD38 CSCs could be possible useful diagnostic markers for pediatric ALL. Also, TIMP-1 is a promising prognostic marker for poor outcome of the patients.

In addition, TIMP1 positively correlated with the p53 signaling pathway, complement, and coagulation cascades involved in TC. The present study provided seven prognosis-associated genes in TC and revealed several significant pathways, which contributed to elucidate the pathogenesis of TC.

It is concluded that TIMP1 (rs4898) and TIMP3 (rs9619311) polymorphisms are not significantly related to breast cancer. Moreover, CC and TT genotypes are correlated with increased serum TIMP1 and TIMP3 levels in breast cancer patients, respectively. It is also suggested that serum concentration of TIMP1 and TIMP3 is related to the physiopathology of breast cancer.

Both TIMP-1-positive IHC staining and high serum/plasma TIMP-1 levels are poor prognostic factors for the survival of gastrointestinal cancer. In addition, TIMP-1 overexpression was correlated with more advanced clinicopathological features.

Further analysis revealed that FBN1/TIMP1 interaction could improve DLBCL cell migration and regulate the Wnt signaling pathway. Although the underlying mechanisms regarding the interaction between FBN1 and TIMP1 requires further clarification, they might be potential therapeutic targets for DLBCL therapy.

Experimental results indicated that overexpression of TIMP1 inhibited the proliferation and migration, while it had no significant effect on invasion of UM cells. Our study indicates that TIMP1 might be associated with metastasis in UM, which might have important significance for identifying patients with high risk of metastasis and predicting the prognosis of UM.

In conclusion, we construct a novel prognostic model which provides new insights into glioma prognosis. The PDPN and TIMP1 may serve as potential biomarkers for prognosis of glioma.

By coexpression networks analysis, competing endogenous RNA (ceRNA) network analysis, cell proliferation assay and luciferase reporter assay, we confirmed that lncRNA HOXA-AS2 functioned as a ceRNA for miR-184 to regulate expression of COL6A2, which induced cell proliferation of low-grade glioma. In this study, we revealed a 3-hub protein-coding gene signature to improve prognostic prediction in LGG, and identified a critical ceRNA regulation involved in LGG recurrence.

Different types of treatment are available for patients with advanced metastatic colorectal cancer, including targeted biological agents, such as cetuximab, a monoclonal antibody that targets EGFR...In addition, TIMP-1 inhibited c-Kit shedding in CRC cells grown in the presence of exogenous TIMP-1. Given the regulatory roles that c-Kit plays in cell proliferation and migration, and the realization that c-Kit is an important oncogene in CRC, it is likely that some of the biological effects of TIMP-1 overexpression in CRC may be exerted through its effect on c-Kit signaling.

When Bax was activated by BAM7 or Bcl-2 was inhibited by venetoclax, CCK-8 assays demonstrated that GEM sensitivity was restored in GEM-resistant cells. The observations that TIMP1 knockdown enhanced GEM sensitivity and reversed chemoresistance by inducing cells apoptosis indicated cooperative antitumor effects of shTIMP1 and GEM therapy on PDAC cells. The combination may be a potential strategy for PDAC therapy.