Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies and is known for its high resistance and low response to treatment. Tumor immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Karyopherin alpha 2 (KPNA2), a member of the nuclear transporter family, is elevated in multiple human cancers and accelerates carcinogenesis. However, the specific role of KPNA2 in PDAC remains unclear. In this study, we found that expression of KPNA2 was significantly upregulated in PDAC compared to adjacent nontumor tissue and its high expression was correlated with poor survival outcome by analyzing the GEO datasets. Similar KPNA2 expression pattern was also found in both human patient samples and KPC mouse models through IHC staining. Although KPNA2 knockdown failed to impair the vitality and migration ability of PDAC cells in vitro, the in vivo tumor growth was significantly impeded and the expression of immune checkpoint ligand PD-L1 was reduced by silencing KPNA2. Furthermore, we uncovered that KPNA2 modulated the expression of PD-L1 by mediating nuclear translocation of STAT3. Collectively, our data suggested that KPNA2 has the potential to serve as a promising biomarker for diagnosis in PDAC.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is among the most metastatic and lethal cancers in humans; once diagnosed, it is usually in the advanced stage, and the 5-year survival rate is about 9% [1]
We compared the expression of nuclear import adaptors between the GTEx dataset and PDAC samples in the TCGA dataset to determine the potential maladjustment genes involved in tumor progression
High expression of Karyopherin alpha 2 (KPNA2) in cancer tissues was significantly associated with a poor prognosis in patients with PDAC (Figures 1(g) and (h))
Summary
Pancreatic ductal adenocarcinoma (PDAC) is among the most metastatic and lethal cancers in humans; once diagnosed, it is usually in the advanced stage, and the 5-year survival rate is about 9% [1]. To find clues useful for early detection and effective therapy for PDAC, there is much interest in tumor histopathology and molecular characteristics of tumor cells. The suppressive tumor microenvironment induced by interactions between cancer cells and stromal cells is critical for PDAC progression and has been implicated in the failure of radiation therapy, chemotherapy, and immunotherapy [2]. Decoding cross-talk between the tumor and its immune contexture is of great importance for exploiting therapy. Some tumor cells have developed multiple strategies to avoid recognition and elimination by the host immune cells, allowing them to evade immune attack (“immune evasion”) and continue cancer progression [4]. Tumor cells and other cells from the tumor microenvironment can promote an immune privilege status
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