Cancer Research and Treatment

Original Articles

Gastrointestinal cancer

Microbial Dynamics across Molecular Subtypes and Prognostic Significance of Lactobacillus in Gastric Cancer: Soo Kyung Nam, Juhyeong Park, Sujin Oh, Yoonjin Kwak, Cheol Min Shin, Kyoung Un Park, Nak-Jung Kwon, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Han-Kwang Yang, Hye Seung Lee; Cancer Res Treat. 2026;58(3):824-845. Published online July 17, 2025; DOI: https://doi.org/10.4143/crt.2025.449

Abstract PDF Supplementary Material PubReader ePub: Purpose
Recent studies have revealed a diverse gastric microbiota beyond Helicobacter pylori, suggesting a role in gastric cancer (GC). We aimed to investigate the composition and characteristics of the microbiota in GC and non-cancerous gastric mucosa (NC), with a particular focus on their relationship to molecular subtypes.
Materials and Methods
We conducted 16S rRNA sequencing and whole transcriptomic analysis on fresh-frozen GC and NC tissue samples from 192 GC patients, as well as saliva samples from 12 GC patients and 18 healthy individuals. Microsatellite instability (MSI), Epstein-Barr virus (EBV) in situ hybridization, and immunohistochemistry for p53 and E-cadherin were used to define molecular subtypes.
Results
GC tissues exhibited significantly higher diversity compared to matched NC tissues, with microbial profiles marked by decreased Helicobacter and increased Streptococcus, Prevotella, and Lactobacillus. Saliva samples predominantly contained oral bacteria and exhibited distinct microbial profiles from gastric tissues. In GC tissue, Helicobacter abundance was negatively correlated with key immune checkpoint genes (CTLA-4, PDCD1, CD274, and LAG3), whereas Prevotella, Streptococcus, and Fusobacterium were positively correlated. MSI-high and EBV-positive subtypes showed lower levels of Helicobacter but higher levels of Lactobacillus, Prevotella, and Streptococcus compared to the epithelial-mesenchymal transition–like subtype. Notably, within MSI-high GC, a subgroup characterized by Lactobacillus-enriched and otherwise microbiota-depleted profiles was significantly associated with poorer overall and disease-free survival.
Conclusion
These findings underscore distinct microbial patterns across GC molecular subtypes, suggesting potential biomarkers for GC diagnosis and treatment.

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Effector Function Characteristics of Exhausted CD8+ T-Cell in Microsatellite Stable and Unstable Gastric Cancer: Dong-Seok Han, Yoonjin Kwak, Seungho Lee, Soo Kyung Nam, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Nak-Jung Kwon, Hye Seung Lee, Han-Kwang Yang; Cancer Res Treat. 2024;56(4):1146-1163. Published online April 12, 2024; DOI: https://doi.org/10.4143/crt.2024.317

Purpose
Gastric cancer exhibits molecular heterogeneity, with the microsatellite instability–high (MSI-H) subtype drawing attention for its distinct features. Despite a higher survival rate, MSI-H gastric cancer lack significant benefits from conventional chemotherapy. The immune checkpoint inhibitors, presents a potential avenue, but a deeper understanding of the tumor immune microenvironment of MSI-H gastric cancer is essential.
Materials and Methods
We explored the molecular characteristics of CD8+ T-cell subtypes in three MSI-H and three microsatellite stable (MSS) gastric cancer samples using single-cell RNA sequencing and spatial transcriptome analysis.
Results
In MSI-H gastric cancer, significantly higher proportions of effector memory T cell (Tem), exhausted T cell (Tex), proliferative exhausted T cell (pTex), and proliferative T cell were observed, while MSS gastric cancer exhibited significantly higher proportions of mucosal-associated invariant T cell and natural killer T cell. In MSI-H gastric cancer, Tex and pTex exhibited a significant upregulation of the exhaustion marker LAG3, as well as elevated expression of effector function markers such as IFNG, GZMB, GZMH, and GZMK, compared to those in MSS gastric cancer. The interferon γ (IFN-γ) signaling pathway of Tex and pTex was retained compared to those of MSS gastric cancer. The spatial transcriptome analysis demonstrates the IFN-γ signaling pathway between neighboring Tex and malignant cell, showcasing a significantly elevated interaction in MSI-H gastric cancer.
Conclusion
Our study reveals novel finding indicating that IFN-γ signaling pathway is retained in Tex and pTex of MSI-H gastric cancer, offering a comprehensive perspective for future investigations into immunotherapy for gastric cancer.

Citations

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Gallic acid potentiates the tumour-killing function of CD8+ T cells in gastric cancer
Si Chen, HaiBin Wang, Meixu Lei, Yumin Li, Qi Wang, Hengxin Wang, Yifei Shen, Xuejie Su, Yali Zhou
Journal of Pharmacy and Pharmacology.2026;[Epub] CrossRef
Exploring the molecular pathology and tumor microenvironment in gastric cancer liver metastasis
Jialu Zhuang, Chao Hu, Lei Lei, Yimeng Sang, Qi Sun, Hongping Xia
Hepatoma Research.2026;[Epub] CrossRef
Advances in Spatial Multi-Omics in Gastric Cancer
Hongfei Yan, Yang Liu
Cells.2026; 15(6): 535. CrossRef
Immunotherapy rechallenge in gastric cancer: resistance mechanisms, molecular stratification, and precision decision-making
Yu-cai Jiang, Lin-lin Zheng, Ming-gui Fu, Bi-jin Zheng
Frontiers in Immunology.2026;[Epub] CrossRef
Precision oncology in gastric cancer: navigating molecular subtypes, therapeutic targets, and future horizons
Yanyun Hong, Xiaodong Wang, Hang Yu, Xiaosun Liu, Chao Tang
Cellular Oncology.2026;[Epub] CrossRef
Neurogranin facilitates maintaining the immunosuppressive state of hepatocellular carcinoma by promoting TGF-β1 secretion
Dongjie Ye, Zhu Zhang, Yuxin Yao, Banglun Pan, Hao Wu, Xinyu Zhang, Xiaoqian Wang, Nanhong Tang
International Journal of Biological Macromolecules.2025; 311: 143716. CrossRef
T-cell senescence: Unlocking the tumor immune “Dark Box” - A multidimensional analysis from mechanism to tumor immunotherapeutic intervention
Jia Cheng, Jian Zheng, Chen Ma, Yongzhang Li, Hua Hao
Seminars in Cancer Biology.2025; 113: 190. CrossRef
Hybrid model for predicting microsatellite instability in colorectal cancer using hematoxylin & eosin-stained images and clinical features
Hangping Wei, Xiaowei Zhang, Zhen Zhou, Jianbin Xie, Weidong Han, Xiaofang Dong
Frontiers in Oncology.2025;[Epub] CrossRef
Simvastatin induces ferroptosis and activates anti-tumor immunity to sensitize anti-PD-1 immunotherapy in microsatellite stable gastric cancer
Yumei Ning, Shilin Fang, Runan Zhang, Jun Fang, Kun Lin, Yang Ding, Haihang Nie, Jingkai Zhou, Qiu Zhao, Hengning Ke, Haizhou Wang, Fan Wang
International Immunopharmacology.2024; 142: 113244. CrossRef

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Genomic and Transcriptomic Characterization of Gastric Cancer with Bone Metastasis: Sujin Oh, Soo Kyung Nam, Keun-Wook Lee, Hye Seung Lee, Yujun Park, Yoonjin Kwak, Kyu Sang Lee, Ji-Won Kim, Jin Won Kim, Minsu Kang, Young Suk Park, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hyung Ho Kim; Cancer Res Treat. 2024;56(1):219-237. Published online August 11, 2023; DOI: https://doi.org/10.4143/crt.2023.340

Abstract PDF Supplementary Material PubReader ePub

Purpose
Bone metastasis (BM) adversely affects the prognosis of gastric cancer (GC). We investigated molecular features and immune microenvironment that characterize GC with BM compared to GC without BM.
Materials and Methods
Targeted DNA and whole transcriptome sequencing were performed using formalin-fixed paraffin-embedded primary tumor tissues (gastrectomy specimens) of 50 GC cases with distant metastases (14 with BM and 36 without BM). In addition, immunohistochemistry (IHC) for mucin-12 and multiplex IHC for immune cell markers were performed.
Results
Most GC cases with BM had a histologic type of poorly cohesive carcinoma and showed worse overall survival (OS) than GC without BM (p < 0.05). GC with BM tended to have higher mutation rates in TP53, KDR, APC, KDM5A, and RHOA than GC without BM. Chief cell-enriched genes (PGA3, PGC, and LIPF), MUC12, MFSD4A, TSPAN7, and TRIM50 were upregulated in GC with BM compared to GC without BM, which was correlated with poor OS (p < 0.05). However, the expression of SERPINA6, SLC30A2, PMAIP1, and ITIH2 were downregulated in GC with BM. GC with BM was associated with PIK3/AKT/mTOR pathway activation, whereas GC without BM showed the opposite effect. The densities of helper, cytotoxic, and regulatory T cells did not differ between the two groups, whereas the densities of macrophages were lower in GC with BM (p < 0.05).
Conclusion
GC with BM had different gene mutation and expression profiles than GC without BM, and had more genetic alterations associated with a poor prognosis.

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Multi-gene DNA methylation profiles of tumor suppressor genes for prognostic prediction in gastric cancer
Soo Kyung Nam, Juhyeong Park, Yoonjin Kwak, Chinbayar Batochir, Eun-Bi Kim, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Han-Kwang Yang, Hye Seung Lee
BMC Cancer.2026;[Epub] CrossRef
Precision treatment of gastrointestinal tumours and liver disease interaction mechanisms based on multi-omics data and microbiome hubs
Bangxing Lin, Shizheng Tong, Chaokai Ba, Xiang Wang
Frontiers in Cellular and Infection Microbiology.2026;[Epub] CrossRef
Microbial Dynamics across Molecular Subtypes and Prognostic Significance of Lactobacillus in Gastric Cancer
Soo Kyung Nam, Juhyeong Park, Sujin Oh, Yoonjin Kwak, Cheol Min Shin, Kyoung Un Park, Nak-Jung Kwon, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Han-Kwang Yang, Hye Seung Lee
Cancer Research and Treatment.2026; 58(3): 824. CrossRef
The genetic architecture of bone metastases: unveiling the role of epigenetic and genetic modifications in drug resistance
Ahmad Dawalibi, Mohamad Bakir, Khalid S. Mohammad
Cancer Drug Resistance.2025;[Epub] CrossRef
TSPAN7 inhibits pancreatic cancer progression by suppressing DNA double-strand break repair and enhances sensitivity to immunochemotherapy
Hai Lin, Jiancong Zhou, Yaning Li, Lisi Luo, Yan Zeng, Xinyue Liang, Jiaping Yu, Chengying Ye, Pengfei Yang, Yujing Lin, Yufang Li, Linjuan Zeng
Biochemical Pharmacology.2025; 242: 117199. CrossRef
UBC9 overexpression promotes proliferation and metastasis in gastric cancer via ATF2
QingShui Wang, ShengZhao Li, YiNing Xu, Yuluo Chen, Chao Xu, QiuYan He, Yan Ye, YiMin Huang, Yue Wu, KeJia Guo, YaJuan Wei, Yide Huang, Yan Liu, Qing Lin, Shanshan Wang, Feng Li, Minghan Huang, FangQin Xue, Yao Lin
World Journal of Surgical Oncology.2025;[Epub] CrossRef
Migrasome-Related Prognostic Genes in Gastric Cancer: A Transcriptomic and Immunotherapeutic Analysis
Wei Qiu, Ke Zhang, Wei Hu, DongSheng Liu
OncoTargets and Therapy.2025; Volume 18: 873. CrossRef
Global and Sex-Stratified Genome-Wide Association Study of Long COVID Based on Patient-Driven Symptom Recall
Sara Polo-Alonso, Álvaro Hernáez, Irene Dégano, Ruth Martí-Lluch, Mel·lina Pinsach-Abuin, Roberto Elosua, Isaac Subirana, Marta Puigmulé, Alexandra Pérez, Raquel Cruz, Silvia Diz-de Almeida, Eulàlia Puigdecanet, Elisabet Selga, Xavier Nogues, Joan Masclan
International Journal of Molecular Sciences.2025; 26(18): 9252. CrossRef
Targeted Sequencing in Gastric Cancer: Association with Tumor Molecular Characteristics and FLOT Therapy Effectiveness
Liudmila V. Spirina, Alexandra V. Avgustinovich, Olga V. Bakina, Sergey G. Afanas’ev, Maxim Yu. Volkov, Sergey V. Vtorushin, Irina V. Kovaleva, Tatyana S. Klyushina, Igor O. Munkuev
Current Issues in Molecular Biology.2024; 46(2): 1281. CrossRef
SLC30A2-Mediated Zinc Metabolism Modulates Gastric Cancer Progression via the Wnt/β-Catenin Signaling Pathway
Fan Li, Xiaohong Zhang, Li Feng, Xingxing Zhang
Frontiers in Bioscience-Landmark.2024;[Epub] CrossRef
Primary mucinous cystadenocarcinoma of the breast: A case report and literature review
Xi Cao, Yongchao Luo, Songjie Shen, Xinyu Ren
Oncology Letters.2024;[Epub] CrossRef

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Ligand-Independent Epidermal Growth Factor Receptor Overexpression Correlates with Poor Prognosis in Colorectal Cancer: Sumi Yun, Yoonjin Kwak, Soo Kyung Nam, An Na Seo, Heung-Kwon Oh, Duck-Woo Kim, Sung-Bum Kang, Hye Seung Lee; Cancer Res Treat. 2018;50(4):1351-1361. Published online January 17, 2018; DOI: https://doi.org/10.4143/crt.2017.487

Abstract PDF Supplementary Material PubReader ePub

Purpose
Molecular treatments targeting epidermal growth factor receptors (EGFRs) are important strategies for advanced colorectal cancer (CRC). However, clinicopathologic implications of EGFRs and EGFR ligand signaling have not been fully evaluated. We evaluated the expression of EGFR ligands and correlation with their receptors, clinicopathologic factors, and patients’ survival with CRC.
Materials and Methods
The expression of EGFR ligands, including heparin binding epidermal growth factor-like growth factor (HBEGF), transforming growth factor (TGF), betacellulin, and epidermal growth factor (EGF), were evaluated in 331 consecutive CRC samples using mRNA in situ hybridization (ISH). We also evaluated the expression status of EGFR, human epidermal growth factor receptor 2 (HER2), HER3, and HER4 using immunohistochemistry and/or silver ISH.
Results
Unlike low incidences of TGF (38.1%), betacellulin (7.9%), and EGF (2.1%), HBEGF expression was noted in 62.2% of CRC samples. However, the expression of each EGFR ligand did not reveal significant correlations with survival. The combined analyses of EGFR ligands and EGFR expression indicated that the ligands‒/EGFR+ group showed a significant association with the worst disease-free survival (DFS; p=0.018) and overall survival (OS; p=0.005). It was also an independent, unfavorable prognostic factor for DFS (p=0.026) and OS (p=0.007). Additionally, HER4 nuclear expression, regardless of ligand expression, was an independent, favorable prognostic factor for DFS (p=0.034) and OS (p=0.049), by multivariate analysis.
Conclusion
Ligand-independent EGFR overexpression was suggested to have a significant prognostic impact; thus, the expression status of EGFR ligands, in addition to EGFR, might be necessary for predicting patients' outcome in CRC.

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Biology.2025; 14(9): 1225. CrossRef
Systematic literature review and meta-analysis of HER2 amplification, overexpression, and positivity in colorectal cancer
Harshabad Singh, Ashley Kang, Lisa Bloudek, Ling-I Hsu, Maria Corinna Palanca-Wessels, Michael Stecher, Muriel Siadak, Kimmie Ng
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Molecular characterization of colorectal mucinous adenocarcinoma and adenocarcinoma, not otherwise specified, identified by multiomic data analysis
Kailun Xu, Shu Zheng, Baosheng Li, Yingkuan Shao, Xiaoyang Yin
Frontiers in Molecular Biosciences.2023;[Epub] CrossRef
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Materials Express.2022; 12(2): 220. CrossRef
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Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?
Constantin Stefani, Daniela Miricescu, Iulia-Ioana Stanescu-Spinu, Remus Iulian Nica, Maria Greabu, Alexandra Ripszky Totan, Mariana Jinga
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SOX2 Promotes Brain Metastasis of Breast Cancer by Upregulating the Expression of FSCN1 and HBEGF
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Combined Therapeutic Effects of ¹³¹I-Labeled and 5Fu-Loaded Multifunctional Nanoparticles in Colorectal Cancer

Pingping Wu, Huayun Zhu, Yan Zhuang, Xiaofeng Sun, Ning Gu
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HER4 promotes the progression of colorectal cancer by promoting epithelial‑mesenchymal transition
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