Dataset Information

An aptamer interacting with heat shock protein 70 shows therapeutic effects and prognostic ability in serous ovarian cancer.

ABSTRACT: Ovarian cancer (OvCa) is the most lethal gynecologic malignancy owing to its high chemoresistance and late diagnosis, which lead to a poor prognosis. Hence, developing new therapeutic modalities is important for OvCa patient treatment. Our previous results indicated that a novel aptamer, Tx-01, can specifically recognize serous carcinoma cells and tissues. Here, we aim to clarify the clinical role and possible molecular mechanisms of Tx-01 in OvCa. Immunostaining and statistical analysis were performed to detect the interaction of Tx-01 and heat shock protein 70/Notch1 intracellular domain (HSP70/NICD) in OvCa. The in vitro and in vivo experiments were carried out to demonstrate the potential mechanisms of Tx-01. Results show that Tx-01 reduced serous OvCa OVCAR3 cell migration and invasion and inhibited HSP70 nuclear translocation by interrupting the intracellular HSP70/NICD interaction. Furthermore, Tx-01 suppressed serous-type OVCAR3 cell tumor growth in vivo. Tx-01 acts as a prognostic factor through its interaction with membrane-bound HSP70 (mHSP70 that locates on the cell surface without direct interaction to NICD) on ascitic circulating tumor cells (CTCs) and is reported to be involved in natural killer (NK) cell recognition and activation. Our data demonstrated that Tx-01 interacted with HSP70 and showed therapeutic and prognostic effects in serous OvCa. Tx-01 might be a potential inhibitor for use in serous OvCa treatment.

SUBMITTER: Lin CN

PROVIDER: S-EPMC7868721 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

An aptamer interacting with heat shock protein 70 shows therapeutic effects and prognostic ability in serous ovarian cancer.

Lin Chang-Ni CN Tsai Yi-Cheng YC Hsu Ching-Cheng CC Liang Yu-Ling YL Wu Yi-Ying YY Kang Chieh-Yi CY Lin Chun-Hong CH Hsu Pang-Hung PH Lee Gwo-Bin GB Hsu Keng-Fu KF

Molecular therapy. Nucleic acids 20210105

Ovarian cancer (OvCa) is the most lethal gynecologic malignancy owing to its high chemoresistance and late diagnosis, which lead to a poor prognosis. Hence, developing new therapeutic modalities is important for OvCa patient treatment. Our previous results indicated that a novel aptamer, Tx-01, can specifically recognize serous carcinoma cells and tissues. Here, we aim to clarify the clinical role and possible molecular mechanisms of Tx-01 in OvCa. Immunostaining and statistical analysis were pe ...[more]

PMID: 33614227

Similar Datasets

Project description:Heat shock proteins (HSPs) are evolutionarily conserved chaperones occurring in virtually all living organisms playing a key role in the maintenance of cellular homeostasis. They are constitutively expressed to prevent and repair protein damage following various physiological and environmental stressors. HSPs are overexpressed in various types of cancers to provide cytoprotective function, and they have been described to influence prognosis and response to therapy. Moreover, they have been used as a tumor marker in blood serum biochemistry and they represent a potentially promising therapeutic target. To clarify prognostic significance of two canonical HSPs (27 and 70) and less known HSP110 (previously known as HSP105) in colorectal carcinoma (CRC), we retrospectively performed HSP immunohistochemistry on tissue microarrays from formalin-fixed paraffin-embedded tumor tissue from 297 patients with known follow-up. Survival analysis (univariate Kaplan-Meier analysis with the log-rank test and multivariate Cox regression) revealed significantly shorter overall survival (OS, mean 5.54 vs. 7.07, p = 0.033) and borderline insignificantly shorter cancer specific survival (CSS, mean 6.3 vs. 7.87 years, p = 0.066) in patients with HSP70+ tumors. In the case of HSP27+ tumors, there was an insignificantly shorter OS (mean 6.36 vs. 7.13 years, p = 0.2) and CSS (mean 7.17 vs. 7.95 years, p = 0.2). HSP110 showed no significant impact on survival. Using Pearson's chi-squared test, there was a significant association of HSP27 and HSP70 expression with advanced cancer stage. HSP27+ tumors were more frequently mismatch-repair proficient and vice versa (p = 0.014), and they occurred more often in female patients and vice versa (p = 0.015). There was an enrichment of left sided tumors with HSP110+ compared to the right sided (p = 0.022). In multivariate Cox regression adjusted on the UICC stage, grade and right/left side; both HSPs 27 and 70 were not independent survival predictors (p = 0.616 & p = 0.586). In multivariate analysis, only advanced UICC stage (p = 0) and right sided localization (p = 0.04) were independent predictors of worse CSS. In conclusion, from all three HSPs examined in our study, only HSP70 expression worsened CRC prognosis, although stage-dependent. The contribution of this article may be seen as a large survival analysis of HSPs 27 and 70 and the largest analysis of HSP110 described in CRC.

Dataset Information

An aptamer interacting with heat shock protein 70 shows therapeutic effects and prognostic ability in serous ovarian cancer.

Publications

An aptamer interacting with heat shock protein 70 shows therapeutic effects and prognostic ability in serous ovarian cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets