Identification and validation of H. pylori-associated gastric cancer biomarkers in Chinese and German populations
Final Report Abstract
The project aimed to improve the early detection and biological understanding of gastric cancer (GC) by identifying novel molecular markers and validating them functionally in relevant models. The project combined genomic, epigenetic, proteomic, and serological approaches and leveraged a longstanding collaboration between the Technical University of Munich (TUM) and Peking University. Key achievements of the project include the development of two integrated, noninvasive biomarker models for gastric cancer screening and risk stratification. These models combine methylation markers, gene mutations, and *Helicobacter pylori* -specific antibody profiles derived from cell-free DNA and blood samples. Validated in a large, prospective, endoscopically monitored cohort from Linqu County, China —a high-incidence GC region—these models demonstrated high predictive power and are being considered for translational development. The corresponding findings have been published in the *International Journal of Cancer*. The project produced a broad portfolio of scientific outputs, including eight peer-reviewed publications across high-impact journals such as JAMA Network Open, Theranostics, Cell Reports Medicine, etc. The papers covered complementary biomarker strategies—ranging from proteomics and metabolomics to serological and genomic assays—as well as a systematic review of cell-free DNA for GC detection. The results from these diverse methodologies converge to support the feasibility of precision, noninvasive screening approaches for gastric cancer. In addition, the project generated a comprehensive systematic review of cell -free DNA as a diagnostic tool for GC as well as multiple original publications on proteomic and metabolomic signatures in plasma and urine, further enhancing the potential for noninvasive diagnostics. Functional studies on frequently mutated genes in GC, including RNF43 and ACVR2A, were conducted using CRISPR/Cas9-edited gastric cell lines and a newly developed transgenic mouse model, providing insight into their tumor-suppressive roles. Despite organizational challenges caused by the COVID-19 pandemic, the project fulfilled its scientific goals and generated a strong foundation for future translational studies and clinical validation of early GC detection tools.
Publications
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Loss of endogenous RNF43 function enhances proliferation and tumour growth of intestinal and gastric cells. Carcinogenesis, 40(4), 551-559.
Neumeyer, Victoria; Grandl, Martina; Dietl, Alisa; Brutau-Abia, Anna; Allgäuer, Michael; Kalali, Behnam; Zhang, Yang; Pan, Kai-Feng; Steiger, Katja; Vieth, Michael; Anton, Martina; Mejías-Luque, Raquel & Gerhard, Markus
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Methylation and Expression of Nonclustered Protocadherins Encoding Genes and Risk of Precancerous Gastric Lesions in a High-Risk Population. Cancer Prevention Research, 11(11), 717-726.
Wu, Si; Zhang, Yang; Zhang, Lian; Ma, Jun-Ling; Zhou, Tong; Li, Zhe-Xuan; Liu, Wei-Dong; Li, Wen-Qing; You, Wei-Cheng & Pan, Kai-Feng
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Validation of a Blood Biomarker for Identification of Individuals at High Risk for Gastric Cancer. Cancer Epidemiology, Biomarkers & Prevention, 27(12), 1472-1479.
Epplein, Meira; Butt, Julia; Zhang, Yang; Hendrix, Laura H.; Abnet, Christian C.; Murphy, Gwen; Zheng, Wei; Shu, Xiao-Ou; Tsugane, Shoichiro; Qiao, You-lin; Taylor, Philip R.; Shimazu, Taichi; Yoo, Keun-Young; Park, Sue K.; Kim, Jeongseon; Jee, Sun Ha; Waterboer, Tim; Pawlita, Michael; You, Wei-cheng & Pan, Kai-feng
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Telomere Length of Circulating Cell-Free DNA and Gastric Cancer in a Chinese Population at High-Risk. Frontiers in Oncology, 9.
Shi, Yu; Zhang, Yang; Zhang, Lian; Ma, Jun-Ling; Zhou, Tong; Li, Zhe-Xuan; Liu, Wei-Dong; Li, Wen-Qing; Deng, Da-Jun; You, Wei-Cheng & Pan, Kai-Feng
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Whole Genome Messenger RNA Profiling Identifies a Novel Signature to Predict Gastric Cancer Survival. Clinical and Translational Gastroenterology, 10(1), e00004.
Dai, Jin; Li, Zhe-Xuan; Zhang, Yang; Ma, Jun-Ling; Zhou, Tong; You, Wei-Cheng; Li, Wen-Qing & Pan, Kai-Feng
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DNA methylation signatures associated with prognosis of gastric cancer. BMC Cancer, 21(1).
Dai, Jin; Nishi, Akihiro; Li, Zhe-Xuan; Zhang, Yang; Zhou, Tong; You, Wei-Cheng; Li, Wen-Qing & Pan, Kai-Feng
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Helicobacter pylori associated aberrant methylation genes in blood leukocyte and gastric mucosa. Journal of Cancer, 12(24), 7326-7333.
Zhang, Yang; Chen, Duo; Zhang, Lian; Ma, Jun-Ling; Zhou, Tong; Li, Zhe-Xuan; Liu, Wei-Dong; You, Wei-Cheng & Pan, Kai-Feng
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Identification and Validation of Plasma Metabolomic Signatures in Precancerous Gastric Lesions That Progress to Cancer. JAMA Network Open, 4(6), e2114186.
Huang, Sha; Guo, Yang; Li, Zhong-Wu; Shui, Guanghou; Tian, He; Li, Bo-Wen; Kadeerhan, Gaohaer; Li, Zhe-Xuan; Li, Xue; Zhang, Yang; Zhou, Tong; You, Wei-Cheng; Pan, Kai-Feng & Li, Wen-Qing
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Microbiota alteration at different stages in gastric lesion progression: a population-based study in Linqu, China. Am J Cancer Res. 2021;11(2):561–575
Kadeerhan G., Gerhard M., Gao J.J., Mejías-Luque R., Zhang L., Vieth M., Ma J.L., Bajbouj M., Suchanek S., Liu W.D., Ulm K., Quante M., Li Z.X., Zhou T., Schmid R., Classen M., Li W.Q., Zhang Y., You W.C. & Pan K.F.
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Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer. eBioMedicine, 74, 103714.
Li, Xue; Zheng, Nai-Ren; Wang, Lin-Heng; Li, Zhong-Wu; Liu, Zong-Chao; Fan, Hua; Wang, Yi; Dai, Jin; Ni, Xiao-Tian; Wei, Xin; Liu, Ming-Wei; Li, Kai; Li, Zhe-Xuan; Zhou, Tong; Zhang, Yang; Zhang, Jing-Ying; Kadeerhan, Gaohaer; Huang, Sha; Wu, Wen-Hui ... & Qin, Jun
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Characterization of RNF43 mutations in gastric cancer in vitro and in vivo.
Presented at the European Association for Cancer Research (EACR), 2022
Wang M., Mejias-Luque R. & Gerhard M.
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Plasma lipids signify the progression of precancerous gastric lesions to gastric cancer: a prospective targeted lipidomics study. Theranostics, 12(10), 4671-4683.
Liu, Zong-Chao; Wu, Wen-Hui; Huang, Sha; Li, Zhong-Wu; Li, Xue; Shui, Guang-Hou; Lam, Sin Man; Li, Bo-Wen; Li, Zhe-Xuan; Zhang, Yang; Zhou, Tong; You, Wei-Cheng; Pan, Kai-Feng & Li, Wen-Qing
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Urine proteomic signatures predicting the progression from premalignancy to malignant gastric cancer. eBioMedicine, 86, 104340.
Fan, Hua; Li, Xue; Li, Zhong-Wu; Zheng, Nai-Ren; Cao, Li-Hua; Liu, Zong-Chao; Liu, Ming-Wei; Li, Kai; Wu, Wen-Hui; Li, Zhe-Xuan; Zhou, Tong; Zhang, Yang; Liu, Wei-Dong; Zhang, Lan-Fu; You, Wei-Cheng; Wang, Yi; Wu, Jianmin; Pan, Kai-Feng; Qin, Jun & Li, Wen-Qing
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A noninvasive multianalytical approach establishment for risk assessment and gastric cancer screening. International Journal of Cancer, 154(6), 1111-1123.
Fan, Xiao‐Han; Zhang, Yang; Wang, Pei; Song, Qian‐Qian; Wang, Mona; Mejias‐Luque, Raquel; Li, Zhe‐Xuan; Zhou, Tong; Zhang, Jing‐Ying; Liu, Wei‐Dong; Zhang, Lan‐Fu; Li, Wen‐Qing; You, Wei‐Cheng; Gerhard, Markus; Jiao, Yu‐Chen; Wang, Xiao‐Bing & Pan, Kai‐Feng
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Metabolite Alterations and Interactions with Microbiota in Helicobacter pylori-Associated Gastric Lesions. Microbiology Spectrum, 11(4).
Peng, Lei; Guo, Yang; Gerhard, Markus; Gao, Juan-Juan; Liu, Zong-Chao; Mejías-Luque, Raquel; Zhang, Lian; Vieth, Michael; Ma, Jun-Ling; Liu, Wei-Dong; Li, Zhe-Xuan; Zhou, Tong; Li, Wen-Qing; You, Wei-Cheng; Zhang, Yang & Pan, Kai-Feng
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Multi-Omics Approaches to Early Gastric Cancer Detection: Development and Validation of Risk Prediction Models.
PhD Thesis, Technical University of Munich
Wang M.
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Gastric cancer detection based on cell‐free DNA in blood: A systematic review and meta‐analysis. Clinical and Translational Discovery, 4(4).
Wang, Mona; Fan, Xiaohan; Huang, Boyang; Pan, Kaifeng; Gerhard, Markus; Mejías‐Luque, Raquel & Zhang, Yang
