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PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in nasopharyngeal carcinoma
Ranran Feng, Yilin Guo, Meilin Chen, Ziying Tian, Yijun Liu, Su Jiang, Jieyu Zhou, Qingluan Liu, Xiayu Li, Wei Xiong, Lei Shi, Songqing Fan, Guiyuan Li, Wenling Zhang
J Pathol Transl Med. 2025;59(1):68-83.   Published online January 15, 2025
DOI: https://doi.org/10.4132/jptm.2024.11.27
  • 891 View
  • 105 Download
AbstractAbstract PDFSupplementary Material
Background
Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear.
Methods
We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP).
Results
We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin.
Conclusions
PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.
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Elevated expression of Axin2 in intestinal metaplasia and gastric cancers
Dong Hui Lee, In Ho Jeong, Bogun Jang
J Pathol Transl Med. 2023;57(6):315-322.   Published online November 7, 2023
DOI: https://doi.org/10.4132/jptm.2023.10.12
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  • 211 Download
  • 1 Web of Science
  • 2 Crossref
AbstractAbstract PDF
Background
The Wnt signaling pathway regulates crucial cellular processes, including stem cell development and tissue repair. Dysregulation of this pathway, particularly β-catenin stabilization, is linked to colorectal carcinoma and other tumors. Axin2, a critical component in the pathway, plays a role in β-catenin regulation. This study examines Axin2 expression in normal gastric mucosa and various gastric pathologies.
Methods
Formalin-fixed and paraffin-embedded tissue samples from normal stomach, gastritis, intestinal metaplasia (IM), and gastric carcinoma were collected. Axin2 and β-catenin expression were evaluated using RNA in situ hybridization and immunohistochemistry, respectively. Histo-scores (H-scores) were calculated to quantify expression levels of Axin2. Associations between Axin2 expression and clinicopathological variables were examined.
Results
Axin2 expression was examined in normal stomach, gastritis, and IM tissues. Axin2 expression was mainly observed in the surface and isthmus areas in the normal stomach and gastritis, whereas Axin2 expression was markedly higher at the bases of IM. Axin2 H-scores were significantly elevated in IM (mean ± standard deviation [SD], 87.0 ± 38.9) compared to normal (mean ± SD, 18.0 ± 4.5) and gastritis tissues (mean ± SD, 33.0 ± 18.6). In total, 30% of gastric carcinomas showed higher Axin2 expression. Axin2 expression did not have significant associations with age, sex, Lauren classification, histological differentiation, invasion depth, and lymph node metastasis. However, a strong positive correlation was observed between Axin2 and nuclear β-catenin in gastric carcinomas (p < .001).
Conclusions
Axin2 expression was significantly increased in IM compared to normal and gastritis cases. In addition, Axin2 showed a strong positive association with nuclear β-catenin expression in gastric carcinomas, demonstrating a close relationship with abnormal Wnt/β-catenin signaling pathway.

Citations

Citations to this article as recorded by  
  • Refining NTRK Fusion Detection in Papillary Thyroid Carcinoma Through Pan-TRK Immunohistochemistry and Histopathologic Features
    Hyun Lee, Sue Youn Kim, Ji Min Park, Seung-Hyun Jung, Ozgur Mete, Chan Kwon Jung
    Endocrine Pathology.2025;[Epub]     CrossRef
  • A review of potential mechanisms and treatments of gastric intestinal metaplasia
    Yueyao Wu, Kehan Zhang, Yichao Zheng, Haifeng Jin
    European Journal of Gastroenterology & Hepatology.2024;[Epub]     CrossRef
Case Study
Hepatocellular Carcinoma Arising in a Huge Hepatocellular Adenoma with Bone Marrow Metaplasia
Hyo Jeong Kang, Hui Jeong Jeong, So-Woon Kim, Eunsil Yu, Young-Joo Lee, So Yeon Kim, Jihun Kim
J Pathol Transl Med. 2018;52(4):226-231.   Published online December 27, 2017
DOI: https://doi.org/10.4132/jptm.2017.11.12
  • 7,042 View
  • 149 Download
  • 5 Web of Science
  • 6 Crossref
AbstractAbstract PDF
Hepatocellular adenoma (HCA) is the most common type of benign liver tumor, and its major complication is malignant transformation to hepatocellular carcinoma (HCC). Here, we report a case of HCC arising in HCA with bone marrow metaplasia in a 24-year-old Korean woman who presented with abdominal discomfort. A huge liver mass was found on abdominal ultrasonography. She underwent surgical hepatic resection, and the resected specimen was entirely involved by a 20-cm-sized tumor. Histological review revealed a well differentiated HCC arising from inflammatory HCA with β-catenin nuclear positivity and bone marrow metaplasia that contained hematopoietic cells. This case was unique because malignant transformation, inflammatory type HCA, β-catenin nuclear staining, and bone marrow metaplasia were simultaneously observed. Additionally, it should be noted that a large HCA with β-catenin activation can undergo malignant transformation and should be surgically resected in a timely manner.

Citations

Citations to this article as recorded by  
  • Adult Hepatocellular Carcinoma Coexisting with Extramedullary Hematopoiesis
    Hirotsugu Noguchi, Michiyo Higashi, Ryo Desaki, Takashi Tasaki, Mari Kirishima, Ikumi Kitazono, Kazuhiro Tabata, Akihide Tanimoto
    International Journal of Surgical Pathology.2022; 30(3): 339.     CrossRef
  • Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice
    Wenhua Shao, Orgil Jargalsaikhan, Mayuko Ichimura-Shimizu, Qinyi Cai, Hirohisa Ogawa, Yuko Miyakami, Kengo Atsumi, Mitsuru Tomita, Mitsuko Sutoh, Shunji Toyohara, Ryoji Hokao, Yasusei Kudo, Takeshi Oya, Koichi Tsuneyama
    International Journal of Molecular Sciences.2022; 23(19): 11923.     CrossRef
  • Bilateral Diffuse Nodular Pulmonary Ossification Mimicking Metastatic Disease in a Patient with Fibrolamellar Hepatocellular Carcinoma
    Pattamon Sutthatarn, Cara E. Morin, Jessica Gartrell, Wayne L. Furman, Max R. Langham, Teresa Santiago, Andrew J. Murphy
    Children.2021; 8(3): 226.     CrossRef
  • Malignant transformation of liver fatty acid binding protein-deficient hepatocellular adenomas: histopathologic spectrum of a rare phenomenon
    Juan Putra, Linda D. Ferrell, Annette S.H. Gouw, Valerie Paradis, Arvind Rishi, Christine Sempoux, Charles Balabaud, Swan N. Thung, Paulette Bioulac-Sage
    Modern Pathology.2020; 33(4): 665.     CrossRef
  • Hepatocellular carcinoma arising from hepatic adenoma in a young woman
    Haythem Yacoub, Hela Kchir, Dhouha Cherif, Hajer Hassine, Slim Haouet, Asma Ayari, Habiba Mizouni, Saber Mannai, Mohamed Tahar Khalfallah, Nadia Maamouri
    Clinical Case Reports.2020; 8(9): 1659.     CrossRef
  • Metanephric adenoma with osseous metaplasia and bone marrow elements
    Alessandro Pietro Aldera, Jeff John, Dharshnee Chetty, Dhirendra Govender
    Human Pathology: Case Reports.2019; 17: 200316.     CrossRef

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