A Comprehensive Bioinformatics Analysis of TIMP2 in Multiple Malignancies

Background: Tissue inhibitor of metalloproteinase-2 (TIMP2), an endogenous inhibitor of matrix metalloproteinases, has been disclosed to participate in the development and carcinogenesis of multiple malignancies. However, the prognosis of TIMP2 in different cancers and its correlation with tumor microenvironment and immunity have not been clarified.Methods: In this study, we conducted a comprehensive bioinformatics analysis to evaluate the prognostic and therapeutic value of TIMP2 in cancer patients by utilizing a series of databases, including ONCOMINE, GEPIA, cBioPortal, GeneMANIA, Metascape, and Sangerbox online tool. The expression of TIMP2 in different cancers were analyzed by Oncomine, TCGA and GTEx databases and mutation status of TIMP2 in cancers was then verified using cBioportal database. The protein-protein interaction (PPI) network of the TIMP family was exhibited by GeneMANIA. The prognosis of TIMP2 in cancers was performed though GEPIA database and cox regression. Additionally, the correlations between TIMP2 expression and immunity (immune cells, gene markers of immune cells, TMB, MSI, and neoantigen) were explored using Sangerbox online tool.Results: The transcriptional level of TIMP2 in most cancerous tissues were significantly elevated. Survival analysis revealed that elevated expression of TIMP2 was associated with unfavorable survival outcome in multiple cancers. Enrichment analysis demonstrated the possible mechanisms of TIMPs and their associated genes mainly involved in pathways including extracellular matrix (ECM) regulators, degradation of ECM and ECM disassembly, and several other signaling pathways. Conclusions: Our findings systematically dissected that TIMP2 was a potential prognostic maker in various cancers and use the inhibitor of TIMP2 may be an effective strategy for cancer therapy to improve the poor cancer survival and prognostic accuracy, but concrete mechanisms need to be validated by subsequent experiments.

A Comprehensive Bioinformatics Analysis of TIMP2 in Multiple Malignancies

Background: Tissue inhibitor of metalloproteinase-2 (TIMP2), an endogenous inhibitor of matrix metalloproteinases, has been disclosed to participate in the development and carcinogenesis of multiple malignancies. However, the prognosis of TIMP2 in different cancers and its correlation with tumor microenvironment and immunity have not been clarified.Methods: In this study, we conducted a comprehensive bioinformatics analysis to evaluate the prognostic and therapeutic value of TIMP2 in cancer patients by utilizing a series of databases, including ONCOMINE, GEPIA, cBioPortal, GeneMANIA, Metascape, and Sangerbox online tool. The expression of TIMP2 in different cancers were analyzed by Oncomine, TCGA and GTEx databases and mutation status of TIMP2 in cancers was then verified using cBioportal database. The protein-protein interaction (PPI) network of the TIMP family was exhibited by GeneMANIA. The prognosis of TIMP2 in cancers was performed though GEPIA database and cox regression. Additionally, the correlations between TIMP2 expression and immunity (immune cells, gene markers of immune cells, TMB, MSI, and neoantigen) were explored using Sangerbox online tool.Results: The transcriptional level of TIMP2 in most cancerous tissues were significantly elevated. Survival analysis revealed that elevated expression of TIMP2 was associated with unfavorable survival outcome in multiple cancers. Enrichment analysis demonstrated the possible mechanisms of TIMPs and their associated genes mainly involved in pathways including extracellular matrix (ECM) regulators, degradation of ECM and ECM disassembly, and several other signaling pathways. Conclusions: Our findings systematically dissected that TIMP2 was a potential prognostic maker in various cancers and use the inhibitor of TIMP2 may be an effective strategy for cancer therapy to improve the poor cancer survival and prognostic accuracy, but concrete mechanisms need to be validated by subsequent experiments.

Remarkable response to combined immunochemotherapy in patients with metastatic triple-negative breast cancer

Background: Progress in immunotherapy (IT) has shifted treatment paradigms for multiple malignancies. In March 2019, the combination of nab-paclitaxel and atezolizumab was approved by the US FDA for patients with PD-L1 positive metastatic triple-negative breast cancer based on positive results of the Impassion130 trial. Although numerous studies have examined the prognostic role of PD-L1, the value of this test remains controversial. Results: Here, we presented the cases of three heavily pretreated women with metastatic triple-negative breast cancer who exhibited remarkable responses to combined IT and chemotherapy despite undetectable PD-L1. Conclusion: In our opinion, the current FDA-approved assessment for PD-L1 expression is a reasonable tool for deciding whether to start IT. However, because this approach has many limitations, patients with undetectable PD-L1 expression should still be considered for IT.

Primary multiple synchronous tumors: soft tissue sarcoma of the retroperitoneal space and metastatic prostate cancer

At the present time primary-multiple malignancies are of interest in connection with the frequency of prevalence, which remains at the rather high level and continues to grow up, therefore increasing the relevance of this pathology in clinical oncology and everyday practice. With the exception of the treatment of primary multiple malignancies requiring a multimodal approach, as well as in the case of the use of complex treatment in conjunction with chemotherapists and radiotherapy specialists. In the past three decades, the development of screening tests that prevent and detect some cancers at an early, more treatable stage, and treatment advances have increased the 5‑year relative survival rate for all cancers to 66%. In addition to concerns about cancer recurrence, survivors also worry about their risk of developing a new cancer. Prostate cancer is a leader in terms of morbidity and mortality in the world, just as often are found in combination with other malignant tumors. However, given the high detectability of prostate cancer, primary patients are currently receiving radical treatment, and if metastatic prostate cancer is detected, they are receiving drug treatment, which improves the survival and quality of life of patients. Soft tissue sarcomas are rare malignant tumors that develop in the connective tissues and remain poorly understood due to the fact that they make up less than 1% of all malignant diseases. One of the main methods for treating soft tissue sarcomas is the surgical method. Soft tissue sarcomas are difficult to treat and therefore it is imperative that surgeons and other specialists have experience in treating this disease. Studies show that patients with this pathology show better results if they receive treatment in specialized cancer centers that have experience in treating soft tissue sarcoma. This article demonstrates the clinical case of surgical treatment of a patient with primary multiple retroperitoneal tumors and metastatic prostate cancer.