Hyo Shik Shin, Jae-Il Choi, Hye Won Chung, Hee Jung Park, Hak Park, John Hoon Rim, Jong-Baeck Lim
{"title":"靶向抑制ninurin2通过抑制癌起始细胞促进化疗耐药胃癌的化疗敏感性。","authors":"Hyo Shik Shin, Jae-Il Choi, Hye Won Chung, Hee Jung Park, Hak Park, John Hoon Rim, Jong-Baeck Lim","doi":"10.1186/s40364-025-00792-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The combination of epirubicin, cisplatin, and 5-fluorouracil (ECF) is widely used for gastric cancer treatment. However, cancer cells can acquire chemoresistance over multiple treatment cycles, leading to recurrence. This study aimed to investigate a novel biomarker for predicting ECF resistance and its biological roles in gastric cancer.</p><p><strong>Methods: </strong>ECF-resistant (ECF-R) gastric cancer cell lines were established through stepwise ECF treatment. Transcriptome analysis was performed to identify resistance-related genes, which were validated in tumor organoids and in vivo models. Additionally, gastric cancer patient tumor tissues were analyzed for clinical relevance.</p><p><strong>Results: </strong>Transcriptome analysis revealed that NINJURIN2 and CD44 were highly expressed in ECF-R cells but rarely expressed in normal gastric tissues. NINJURIN2 inhibition significantly increased chemosensitivity to ECF in vitro and in vivo. Liquid chromatography-tandem mass spectrometry identified periostin as a binding partner of NINJURIN2, mediating chemoresistance. Furthermore, VAV2 phosphorylation was markedly upregulated in ECF-R cells but was inhibited by NINJURIN2 knockdown. Clinical analysis showed that high NINJURIN2 expression correlated with poor survival outcomes in gastric cancer patients.</p><p><strong>Conclusion: </strong>Our findings suggest that NINJURIN2 can be used as a novel biomarker for chemoresistant gastric cancer patients and that inhibiting NINJURIN2 along with standard chemotherapy could prevent chemoresistance-associated relapse in gastric cancer.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"84"},"PeriodicalIF":9.5000,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168268/pdf/","citationCount":"0","resultStr":"{\"title\":\"Targeted inhibition of Ninjurin2 promotes chemosensitivity in chemoresistant gastric cancer by suppressing cancer-initiating cells.\",\"authors\":\"Hyo Shik Shin, Jae-Il Choi, Hye Won Chung, Hee Jung Park, Hak Park, John Hoon Rim, Jong-Baeck Lim\",\"doi\":\"10.1186/s40364-025-00792-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The combination of epirubicin, cisplatin, and 5-fluorouracil (ECF) is widely used for gastric cancer treatment. However, cancer cells can acquire chemoresistance over multiple treatment cycles, leading to recurrence. This study aimed to investigate a novel biomarker for predicting ECF resistance and its biological roles in gastric cancer.</p><p><strong>Methods: </strong>ECF-resistant (ECF-R) gastric cancer cell lines were established through stepwise ECF treatment. Transcriptome analysis was performed to identify resistance-related genes, which were validated in tumor organoids and in vivo models. Additionally, gastric cancer patient tumor tissues were analyzed for clinical relevance.</p><p><strong>Results: </strong>Transcriptome analysis revealed that NINJURIN2 and CD44 were highly expressed in ECF-R cells but rarely expressed in normal gastric tissues. NINJURIN2 inhibition significantly increased chemosensitivity to ECF in vitro and in vivo. Liquid chromatography-tandem mass spectrometry identified periostin as a binding partner of NINJURIN2, mediating chemoresistance. Furthermore, VAV2 phosphorylation was markedly upregulated in ECF-R cells but was inhibited by NINJURIN2 knockdown. Clinical analysis showed that high NINJURIN2 expression correlated with poor survival outcomes in gastric cancer patients.</p><p><strong>Conclusion: </strong>Our findings suggest that NINJURIN2 can be used as a novel biomarker for chemoresistant gastric cancer patients and that inhibiting NINJURIN2 along with standard chemotherapy could prevent chemoresistance-associated relapse in gastric cancer.</p>\",\"PeriodicalId\":54225,\"journal\":{\"name\":\"Biomarker Research\",\"volume\":\"13 1\",\"pages\":\"84\"},\"PeriodicalIF\":9.5000,\"publicationDate\":\"2025-06-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168268/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomarker Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s40364-025-00792-0\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomarker Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s40364-025-00792-0","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Targeted inhibition of Ninjurin2 promotes chemosensitivity in chemoresistant gastric cancer by suppressing cancer-initiating cells.
Background: The combination of epirubicin, cisplatin, and 5-fluorouracil (ECF) is widely used for gastric cancer treatment. However, cancer cells can acquire chemoresistance over multiple treatment cycles, leading to recurrence. This study aimed to investigate a novel biomarker for predicting ECF resistance and its biological roles in gastric cancer.
Methods: ECF-resistant (ECF-R) gastric cancer cell lines were established through stepwise ECF treatment. Transcriptome analysis was performed to identify resistance-related genes, which were validated in tumor organoids and in vivo models. Additionally, gastric cancer patient tumor tissues were analyzed for clinical relevance.
Results: Transcriptome analysis revealed that NINJURIN2 and CD44 were highly expressed in ECF-R cells but rarely expressed in normal gastric tissues. NINJURIN2 inhibition significantly increased chemosensitivity to ECF in vitro and in vivo. Liquid chromatography-tandem mass spectrometry identified periostin as a binding partner of NINJURIN2, mediating chemoresistance. Furthermore, VAV2 phosphorylation was markedly upregulated in ECF-R cells but was inhibited by NINJURIN2 knockdown. Clinical analysis showed that high NINJURIN2 expression correlated with poor survival outcomes in gastric cancer patients.
Conclusion: Our findings suggest that NINJURIN2 can be used as a novel biomarker for chemoresistant gastric cancer patients and that inhibiting NINJURIN2 along with standard chemotherapy could prevent chemoresistance-associated relapse in gastric cancer.
Biomarker ResearchBiochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
15.80
自引率
1.80%
发文量
80
审稿时长
10 weeks
期刊介绍：
Biomarker Research, an open-access, peer-reviewed journal, covers all aspects of biomarker investigation. It seeks to publish original discoveries, novel concepts, commentaries, and reviews across various biomedical disciplines. The field of biomarker research has progressed significantly with the rise of personalized medicine and individual health. Biomarkers play a crucial role in drug discovery and development, as well as in disease diagnosis, treatment, prognosis, and prevention, particularly in the genome era.
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