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CircRNAs differentially expressed in brain metastases and primary lung cancer tissues of three pairs of non-small cell lung cancer patients with brain metastases

ABSTRACT: We searched for three NSCLC patients with brain metastases in the First Affiliated Hospital of Nanjing Medical University. After obtaining informed consent, the lung cancer brain metastasis surgical specimens and lung carcinoma in situ puncture specimens were collected from the three patients. The histopathological characteristics were examined using hematoxylin and eosin (H&E) staining. We searched for three pairs of differentially expressed RNAs in brain metastasis tissues and lung carcinoma in situ tissues by ceRNA microarray.

ORGANISM(S): Homo sapiens

PROVIDER: GSE236879 | GEO | 2024/12/31

REPOSITORIES: GEO

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Project description:Gene Expression Profiling of Breast Cancer Patients with Brain Metastases Brain metastases confer the worst prognosis of breast cancer as no therapy exists that prevents or eliminates the cancer from spreading to the brain. We developed a new computational modeling method to derive specific downstream signaling pathways that reveal unknown target-disease connections and new mechanisms for specific cancer subtypes. The model enables us to reposition drugs based on available gene expression data of patients. We applied this model to repurpose known or shelved drugs for brain, lung, and bone metastases of breast cancer with the hypothesis that cancer subtypes have their own specific signaling mechanisms. To test the hypothesis, we addressed the specific CSBs for each metastasis that satisfy that (1) CSB proteins are activated by the maximal number of enriched signaling pathways specific to this metastasis, and (2) CSB proteins involve in the most differential expressed coding-genes specific to the specific breast cancer metastasis. The identified signaling networks for the three types of metastases contain 31, 15, and 18 proteins, respectively, and are used to reposition 15, 9, and 2 drug candidates for the brain, lung, and bone metastases of breast cancer. We performed in vitro and in vivo preclinical experiments as well as analysis on patient tumor specimens to evaluate the targets and repositioned drugs. Two known drugs, Sunitinib (FDA approved for renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumor) and Dasatinib (FDA approved for chronic myelogenous leukemia (CML) after imatinib treatment and Philadelphia chromosome-positive acute lymphoblastic leukemia), were shown to prohibit the metastatic colonization in brain. The TMH-52 cohort includes 11 patients who were examined with brain metastasis at the time of breast cancer diagnosis. The other 41 patients were examined with other organ metastasis at the time of breast cancer diagnosis.

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CircRNAs differentially expressed in brain metastases and primary lung cancer tissues of three pairs of non-small cell lung cancer patients with brain metastases

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