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Li X, Wu N, Wang C, Pei B, Ma X, Xie J, Yang W. NALCN expression is down-regulated and associated with immune infiltration in gastric cancer. Front Immunol 2025; 16:1512107. [PMID: 40013144 PMCID: PMC11860897 DOI: 10.3389/fimmu.2025.1512107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 01/29/2025] [Indexed: 02/28/2025] Open
Abstract
Background NALCN has been identified as a tumor suppressor gene, and its role in human cancer progression has garnered significant attention. However, there is a paucity of experimental studies specifically addressing the relationship between NALCN and immune cell infiltration in gastric cancer (GC). Methods The expression levels of NALCN in tumor tissues, peripheral blood and gastric cancer cells lines from patients with GC were assessed using RNA sequencing, immunohistochemistry (IHC) staining and RT-qPCR. Data obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were utilized to investigate the correlation between NALCN expression and immune cell infiltration in GC. Subsequently, the relationship between NALCN expression and infiltrating immune cells in GC tissues was examined through immunofluorescence method. Additionally, in vitro experiments were conducted to evaluate the impact of NALCN knockdown on T cells function in GC cell lines. Results RNA sequencing analysis revealed that NALCN expression was significantly downregulated in GC tissues. Specifically, NALCN levels were lower in GC tumor tissues and plasma compared to adjacent non-tumor tissues and healthy controls. Consistent with these findings, the expression trend of NALCN mRNA in the GEO database mirrored the experimental results. Mechanistically, NALCN knockdown markedly enhanced cell proliferation, colony formation and migration while reducing apoptosis rates in AGS and GES-1 cells. Analysis of the TCGA database indicated a positive correlation between NALCN expression and the infiltration of B cells, cytotoxic cells, immature dendritic cells (iDC) cells, CD8+ T cells, and others in GC tissue. Conversely, Th17 and Th2 cells infiltration exhibited a negative correlation with NALCN expression. Immunofluorescence staining confirmed that B cells and CD8 T cells were more abundant in GC tumor tissues with high NALCN expression, whereas Th17 and Th2 cells were less prevalent. Subsequently, we co-cultured GC cells transfected with NALCN knockdown or control vectors along with their supernatants with T cells. The results demonstrated that NALCN knockdown in GC cells or their supernatants inhibited T cell proliferation compared to control conditions. Moreover, NALCN may play a role in glucose and glutamine uptake. Conclusions NALCN facilitates immune cell aggregation in GC and has potential as a biomarker for immune infiltration.
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Affiliation(s)
- Xuewei Li
- Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan, China
- MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan, China
| | - Na Wu
- Department of Digestive Oncology, Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
| | - Chen Wang
- Department of Digestive Oncology, Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
| | - Beibei Pei
- Department of Digestive Oncology, Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
| | - Xiaoyan Ma
- Department of Digestive Oncology, Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
| | - Jun Xie
- Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan, China
- MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan, China
| | - Wenhui Yang
- Department of Gastroenterology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
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Wei S, Zhang J, Wu H, Liao Z, Liu Z, Hou Y, Du D, Jiang J, Sun L, Yuan S, Yang M. C118P Suppresses Gastric Cancer Growth via Promoting Autophagy-Lysosomal Degradation of RAB1A. Pharmaceutics 2024; 16:1620. [PMID: 39771598 PMCID: PMC11678531 DOI: 10.3390/pharmaceutics16121620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Revised: 12/16/2024] [Accepted: 12/19/2024] [Indexed: 01/11/2025] Open
Abstract
Background/Objectives: Gastric cancer (GC) is the leading cause of cancer-related deaths worldwide. C118P, a microtubule inhibitor with anti-angiogenic and vascular-disrupting activities, was proven to be cytotoxic to various cancer cell lines. This study aimed to explore the anti-tumor effect of C118P against gastric cancer and identify its potential target. Methods: The MTT assay, colony formation assay, and EdU incorporation assay were used to evaluate the effect of C118P on GC cell proliferation. Cell cycle and cell apoptosis were measured using flow cytometry. Molecular docking, a microscale thermophoresis (MST) analysis, and the cellular thermal shift assay (CETSA) were used to investigate the binding of C118P to RAB1A. Autophagy-related effects were evaluated by using the MDC staining assay, immunofluorescence assay, and immunoblotting assay. The SGC-7901 cell line xenograft mouse model was used to confirm the anti-tumor efficacy of C118P. Results: C118P dramatically inhibited proliferation, induced G2/M cell cycle arrest, and triggered apoptosis in GC cell lines HGC-27 and SGC-7901. Mechanistically, C118P was demonstrated to bind with RAB1A and reduce the RAB1A protein level, accompanied by the inhibition of mTORC1 signaling. Moreover, C118P induced autophagosome formation and promoted RAB1A protein degradation in an autophagy-lysosomal-dependent manner. The in vivo study verified that C118P inhibits GC growth by inhibiting the RAB1A-mTOR axis. Conclusions: Our findings suggested that C118P inhibits GC growth by promoting the autophagy-lysosomal-dependent degradation of RAB1A and modulating mTOR C1 signaling. C118P shows potential as being a small molecule drug effective in the treatment of gastric cancer via targeting RAB1A.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Shengtao Yuan
- New Drug Screening and Pharmacodynamics Evaluation Center, National Key Laboratory for Multi-Target Natural Drugs, China Pharmaceutical University, Nanjing 210009, China; (S.W.); (J.Z.); (H.W.); (Z.L.); (Z.L.); (Y.H.); (D.D.); (J.J.); (L.S.)
| | - Mei Yang
- New Drug Screening and Pharmacodynamics Evaluation Center, National Key Laboratory for Multi-Target Natural Drugs, China Pharmaceutical University, Nanjing 210009, China; (S.W.); (J.Z.); (H.W.); (Z.L.); (Z.L.); (Y.H.); (D.D.); (J.J.); (L.S.)
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Ghosh S, Ghatak D, Dutta R, Goswami D, De R. PINK1 insufficiency can be exploited as a specific target for drug combinations inducing mitochondrial pathology-mediated cell death in gastric adenocarcinoma. Arch Biochem Biophys 2024; 759:110110. [PMID: 39103009 DOI: 10.1016/j.abb.2024.110110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 07/23/2024] [Accepted: 08/02/2024] [Indexed: 08/07/2024]
Abstract
There exist very limited non-hazardous therapeutic strategies except for surgical resection and lymphadenectomy against gastric cancer (GC) despite being the third leading cause of cancer deaths worldwide. This study proposes an innovative treatment approach against GC using a drug combination strategy that manipulates mitochondrial dynamics in conjunction with the induction of mitochondrial pathology-mediated cell death. Comparative analysis was done with gastric adenocarcinoma and normal cells by qPCR, western blot, microscopic immunocytochemistry, and live cell imaging. In this study, impairment of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission by Mdivi-1 created an imbalance in mitochondrial structural dynamics in indomethacin-treated AGS cells in which mitophagy-regulator protein PINK1 is downregulated. These drug combinations with the individual sub-lethal doses ultimately led to the activation of cell death machinery upregulating pro-apoptotic proteins like Bax, Puma, and Noxa. Interestingly, this combinatorial therapy did not affect normal gastric epithelial cells significantly and also no significant upregulation of death markers was observed. Moreover, the drug combination strategy also retarded cell migration and reduced stemness in GC cells. In summary, this study offers a pioneering specific therapeutic strategy for GC treatment, sparing normal cells providing opportunities for minimal drug-mediated toxicity utilizing mitochondria as a viable and specific target for anti-cancer therapy in gastric cancer.
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Affiliation(s)
- Sayak Ghosh
- Amity Institute of Biotechnology, Amity University Kolkata, Plot No: 36, 37 & 38, Major Arterial Road, Action Area II, Kadampukur Village, Newtown, Kolkata, 700135, West Bengal, India
| | - Debapriya Ghatak
- Indian Association for the Cultivation of Science, Jadavpur, Kolkata, 700032, West Bengal, India
| | - Rittick Dutta
- Swami Vivekananda University, Kolkata, 700121, West Bengal, India
| | - Devyani Goswami
- Amity Institute of Biotechnology, Amity University Kolkata, Plot No: 36, 37 & 38, Major Arterial Road, Action Area II, Kadampukur Village, Newtown, Kolkata, 700135, West Bengal, India
| | - Rudranil De
- Amity Institute of Biotechnology, Amity University Kolkata, Plot No: 36, 37 & 38, Major Arterial Road, Action Area II, Kadampukur Village, Newtown, Kolkata, 700135, West Bengal, India.
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Li K, Wang H, Jiang B, Jin X. TRIM28 in cancer and cancer therapy. Front Genet 2024; 15:1431564. [PMID: 39100077 PMCID: PMC11294089 DOI: 10.3389/fgene.2024.1431564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Accepted: 07/01/2024] [Indexed: 08/06/2024] Open
Abstract
TRIM28 (tripartite motif protein 28) was initially believed to be a transcription inhibitor that plays an important role in DNA damage repair (DDR) and in maintaining cancer cellular stemness. As research has continued to deepen, several studies have found that TRIM28 not only has ubiquitin E3 ligase activity to promote degradation of substrates, but also can promote SUMOylation of substrates. Although TRIM28 is highly expressed in various cancer tissues and has oncogenic effects, there are still a few studies indicating that TRIM28 has certain anticancer effects. Additionally, TRIM28 is subject to complex upstream regulation. In this review, we have elaborated on the structure and regulation of TRIM28. At the same time, highlighting the functional role of TRIM28 in tumor development and emphasizing its impact on cancer treatment provides a new direction for future clinical antitumor treatment.
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Affiliation(s)
- Kailang Li
- Department of Oncology and Hematology, Beilun District People’s Hospital, Ningbo, China
| | - Haifeng Wang
- Department of Oncology and Hematology, Beilun District People’s Hospital, Ningbo, China
| | - Bitao Jiang
- Department of Oncology and Hematology, Beilun District People’s Hospital, Ningbo, China
| | - Xiaofeng Jin
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathphysiology, Medical School of Ningbo University, Ningbo, China
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Ma Q, Ma F, Zhang B, Zhang Y, Peng L, Li X. The short peptide encoded by long non-coding RNA RNF217-AS1 inhibits stomach cancer tumorigenesis, macrophage recruitment, and pro-inflammatory responses. Amino Acids 2024; 56:45. [PMID: 39007996 PMCID: PMC11249698 DOI: 10.1007/s00726-024-03404-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 06/24/2024] [Indexed: 07/16/2024]
Abstract
Certain long non-coding RNAs (lncRNAs) have potential peptide-coding abilities. Here, the role and molecular basis of the RNF217-AS1-encoded peptide in stomach cancer (SC) tumorigenesis were explored. Here, lncRNAs associated with SC pathogenesis and macrophage infiltration and lncRNAs with peptide-coding potential were searched by bioinformatics analysis. The gene mRNA and protein levels were examined by RT-qPCR and western blot assays, respectively. Cell viability, migratory, and invasive abilities were measured by CCK-8, Transwell migration, and Transwell invasion assays, respectively. The potential biological processes related to lncRNA RNF217-AS1 were identified by single-gene GSEA analysis. The effect of RNF217-AS1-encoded peptide on SC tumorigenesis was examined by mouse xenograft experiments. The results showed that lncRNA NR2F1-AS1 and RNF217-AS1 were differentially expressed and associated with macrophage infiltration in SC, and they had the ability to translate into short peptides. The RNF217-AS1 ORF-encoded peptide could reduce SC cell viability, inhibit cell migration and invasion, as well as hinder the development of SC xenograft tumors. The RNF217-AS1 ORF-encoded peptide in human SC AGS cells suppressed THP-1 cell migration, triggered the differential expression of CXCL1/CXCL2/CXCL8/CXCL12, and inactivated the TLR4/NF-κB/STAT1 signaling pathways. As a conclusion, the RNF217-AS1 ORF-encoded peptide hindered SC progression in vitro and in vivo and suppressed macrophage recruitment and pro-inflammatory responses in SC.
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Affiliation(s)
- Qi Ma
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, China
| | - Fei Ma
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, China
| | - Bin Zhang
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, China
| | - Yonglei Zhang
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, China
| | - Liangqun Peng
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, China
| | - Xiangnan Li
- Department of Cerebral Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, Henan, 450000, China.
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Liu Y, Jiang X, Yan X, Yang S, Bian X, Wang Y, You Q, Zhang L. Elevated mRNA level indicates FSIP1 promotes EMT and gastric cancer progression by regulating fibroblasts in tumor microenvironment. Open Med (Wars) 2024; 19:20240964. [PMID: 38737444 PMCID: PMC11087735 DOI: 10.1515/med-2024-0964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 04/05/2024] [Accepted: 04/08/2024] [Indexed: 05/14/2024] Open
Abstract
Fiber sheath interaction protein 1 (FSIP1) plays a crucial role in cancer development and occurrence, but its influence on gastric cancer is still unclear. In this study, differential mRNA analysis was performed by TCGA database for the Limma analysis algorithm, and the gene ontology, the Kyoto Encyclopedia of Genes and Genomes, and the gene set enrichment analysis (GSEA) were used for bioinformatics functional enrichment analysis. A gastric cancer cell model with FSIP1 mRNA knockdown was constructed by RNA interference. Cell counting kit-8 and transwell migration/invasion assay were performed to verify the cell function, and western blotting was employed to confirm the expression of target genes. The GSEA analysis revealed that FSIP1 was associated with epithelial-mesenchymal transition (EMT). The high expression group also had a significant positive correlation with the markers of fibroblast in tumor microenvironment (TME). Western blotting showed that FSIP1 was generally upregulated in gastric cancer cell lines. FSIP1 mRNA knockdown cell lines inhibited gastric cells proliferation, migration, and metastasis in vitro, and the protein levels of EMT-related markers N-cadherin and vimentin were reduced. Our work proved that FSIP1 promoted EMT by regulating fibroblasts in the TME, thereby promoting the carcinogenic activity of cancer cells in proliferation, invasion, and migration. FSIP1 may take a role of the occurrence and could be a potential therapeutic target and offer a new insight into the underlying mechanism of gastric cancer.
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Affiliation(s)
- Yao Liu
- Department of Cancer Prevention and Physical Examination Center, Harbin Medical University Cancer Hospital, Harbin, 150081, P. R. China
| | - Xinju Jiang
- Department of Pathology, Harbin Medical University, Harbin, 150076, P. R. China
| | - Xiuchun Yan
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, P. R. China
| | - Shuo Yang
- Department of Pathology, Harbin Medical University, Harbin, 150076, P. R. China
| | - Xiulan Bian
- Department of Pathology, Harbin Medical University, Harbin, 150076, P. R. China
| | - Yue Wang
- Department of Pharmacology & Toxicology, Wright State University, Dayton, 45435, United States of America
| | - Qi You
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, P. R. China
| | - Lei Zhang
- Department of Pathology, Harbin Medical University, Harbin, 150076, P. R. China
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Cao Y, Li Y, Ren C, Yang C, Hao R, Mu T. Manganese-based nanomaterials promote synergistic photo-immunotherapy: green synthesis, underlying mechanisms, and multiple applications. J Mater Chem B 2024; 12:4097-4117. [PMID: 38587869 DOI: 10.1039/d3tb02844e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/09/2024]
Abstract
Single phototherapy and immunotherapy have individually made great achievements in tumor treatment. However, monotherapy has difficulty in balancing accuracy and efficiency. Combining phototherapy with immunotherapy can realize the growth inhibition of distal metastatic tumors and enable the remote monitoring of tumor treatment. The development of nanomaterials with photo-responsiveness and anti-tumor immunity activation ability is crucial for achieving photo-immunotherapy. As immune adjuvants, photosensitizers and photothermal agents, manganese-based nanoparticles (Mn-based NPs) have become a research hotspot owing to their multiple ways of anti-tumor immunity regulation, photothermal conversion and multimodal imaging. However, systematic studies on the synergistic photo-immunotherapy applications of Mn-based NPs are still limited; especially, the green synthesis and mechanism of Mn-based NPs applied in immunotherapy are rarely comprehensively discussed. In this review, the synthesis strategies and function of Mn-based NPs in immunotherapy are first introduced. Next, the different mechanisms and leading applications of Mn-based NPs in immunotherapy are reviewed. In addition, the advantages of Mn-based NPs in synergistic photo-immunotherapy are highlighted. Finally, the challenges and research focus of Mn-based NPs in combination therapy are discussed, which might provide guidance for future personalized cancer therapy.
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Affiliation(s)
- Yuanyuan Cao
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, P. R. China.
- Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, P. R. China
| | - Yilin Li
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, P. R. China.
- Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, P. R. China
| | - Caixia Ren
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, P. R. China.
- Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, P. R. China
| | - Chengkai Yang
- School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P. R. China
| | - Rongzhang Hao
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, P. R. China.
- Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, P. R. China
| | - Tiancheng Mu
- Department of Chemistry, Renmin University of China, Beijing 100872, P. R. China.
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Li J, Xia C, Song Y, Zhang L, Shang W, Xu N, Lu Q, Liang D. Disulfidptosis-related lncRNA signature reveals immune microenvironment and novel molecular subtyping of stomach adenocarcinoma. Heliyon 2024; 10:e29005. [PMID: 38628708 PMCID: PMC11019176 DOI: 10.1016/j.heliyon.2024.e29005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 03/25/2024] [Accepted: 03/28/2024] [Indexed: 04/19/2024] Open
Abstract
The main challenge in treating stomach adenocarcinoma (STAD) is chemotherapy resistance, which is characterized by changes in the immune microenvironment. Disulfidptosis, a novel form of programmed cell death, is involved in STAD but its mechanism is not fully understood. Long non-coding RNAs (LncRNAs) may play a role in regulating disulfidptosis and influencing the immune microenvironment and chemotherapy resistance in STAD. This study aims to establish disulfidptosis-related lncRNA (DRL) features and explore their significance in the immune microenvironment and chemotherapy resistance in STAD patients. By analyzing RNA sequencing and clinical data from STAD patients and extracting disulfidptosis-related genes, we identified DRLs through co-expression, single-factor and multi-factor Cox regression, and Lasso regression analyses. We also investigated differences in the immune microenvironment, immune function, immune checkpoint gene expression, and chemotherapy resistance between different risk groups using various algorithms. A prognostic risk model consisting of 2 DRLs was constructed, with a strong predictive value for patient survival, outperforming other clinical-pathological factors in predicting 3-year and 5-year survival. Immune-related analysis revealed a strong positive correlation between T cell CD4+ cells and risk score across all algorithms, and higher expression of immune checkpoint genes in the high-risk group. In addition, high-risk patients showed better sensitivity to Erlotinib, Oxaliplatin, and Gefitinib. Furthermore, three novel molecular subtypes of STAD were identified based on the 2-DRLs features, with evaluation of the immune microenvironment and chemotherapy drug sensitivity for each subgroup, which holds significant implications for achieving precise treatment in STAD. Overall, our 2-DRLs prognostic model demonstrates high predictive value for patient survival in STAD, potentially providing new targets for individualized immune and chemical therapy.
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Affiliation(s)
- Jinze Li
- Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, 650106, PR China
- Department of Gastrointestinal surgery, The Third People's Hospital of Hubei Province, Wuhan, 430071, PR China
| | - Chuqi Xia
- Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, 650106, PR China
| | - Yilin Song
- Shantou university medical college, 22 xinling Road, Shantou, Guangdong Province, 515041, PR China
| | - Lu Zhang
- Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, 650106, PR China
| | - Wei Shang
- Shiyan People's Hospital of Hubei Medical College, Shi Yan, Hubei Province, 442000, PR China
| | - Ning Xu
- Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, 650106, PR China
| | - Qiyu Lu
- Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, 650106, PR China
| | - Daoming Liang
- Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, 650106, PR China
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Liu K, Wu CX, Liang H, Wang T, Zhang JY, Wang XT. Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis. World J Gastrointest Surg 2024; 16:700-709. [PMID: 38577087 PMCID: PMC10989337 DOI: 10.4240/wjgs.v16.i3.700] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 01/17/2024] [Accepted: 02/20/2024] [Indexed: 03/22/2024] Open
Abstract
BACKGROUND Gastric cancer (GC) is the fifth most common type of cancer and has the fourth highest death rate among all cancers. There is a lack of studies examining the impact of liver metastases on the effectiveness of immunotherapy in individuals diagnosed with GC. AIM To investigate the influence of liver metastases on the effectiveness and safety of immunotherapy in patients with advanced GC. METHODS This retrospective investigation collected clinical data of patients with advanced stomach cancer who had immunotherapy at our hospital from February 2021 to January 2023. The baseline attributes were compared using either the Chi-square test or the Fisher exact probability method. The chi-square test and Kaplan-Meier survival analysis were employed to assess the therapeutic efficacy and survival duration in GC patients with and without liver metastases. RESULTS The analysis comprised 48 patients diagnosed with advanced GC, who were categorized into two groups: A liver metastasis cohort (n = 20) and a non-liver metastatic cohort (n = 28). Patients with liver metastasis exhibited a more deteriorated physical condition compared to those without liver metastasis. The objective response rates in the cohort with metastasis and the cohort without metastasis were 15.0% and 35.7% (P > 0.05), respectively. Similarly, the disease control rates in these two cohorts were 65.0% and 82.1% (P > 0.05), respectively. The median progression-free survival was 5.0 months in one group and 11.2 months in the other group, with a hazard ratio of 0.40 and a significance level (P) less than 0.05. The median overall survival was 12.0 months in one group and 19.0 months in the other group, with a significance level (P) greater than 0.05. CONCLUSION Immunotherapy is less effective in GC patients with liver metastases compared to those without liver metastasis.
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Affiliation(s)
- Kai Liu
- Department of Radiation and Oncology, Traditional Chinese Hospital of Lu’an affiliated to Anhui University of Traditional Chinese Medicine, Lu’an 237000, Anhui Province, China
| | - Chun-Xiao Wu
- Department of Gastroenterology, Ehu branch of Xishan People’s Hospital of Wuxi City, Wuxi 214116, Jiangsu Province, China
| | - Hui Liang
- Department of Radiation and Oncology, Traditional Chinese Hospital of Lu’an affiliated to Anhui University of Traditional Chinese Medicine, Lu’an 237000, Anhui Province, China
| | - Tao Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510400, Guangdong Province, China
| | - Ji-Yuan Zhang
- Department of Gastrointestinal Surgery, Hunan Provincial People’s Hospital, Changsha 410002, Hunan Province, China
| | - Xiao-Tao Wang
- Department of Traditional Chinese medicine, Ehu branch of Xishan People’s Hospital of Wuxi City, Wuxi 214116, Jiangsu Province, China
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10
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Zhang X, Zhang Y, Zhang Q, Lu M, Chen Y, Zhang X, Zhang P. Role of AT-rich interaction domain 1A in gastric cancer immunotherapy: Preclinical and clinical perspectives. J Cell Mol Med 2024; 28:e18063. [PMID: 38041544 PMCID: PMC10902580 DOI: 10.1111/jcmm.18063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 10/31/2023] [Accepted: 11/14/2023] [Indexed: 12/03/2023] Open
Abstract
The application of immune checkpoint inhibitor (ICI) using monoclonal antibodies has brought about a profound transformation in the clinical outcomes for patients grappling with advanced gastric cancer (GC). Nonetheless, despite these achievements, the quest for effective functional biomarkers for ICI therapy remains constrained. Recent research endeavours have shed light on the critical involvement of modified epigenetic regulators in the pathogenesis of gastric tumorigenesis, thus providing a glimpse into potential biomarkers. Among these regulatory factors, AT-rich interaction domain 1A (ARID1A), a pivotal constituent of the switch/sucrose non-fermentable (SWI/SNF) complex, has emerged as a promising candidate. Investigations have unveiled the pivotal role of ARID1A in bridging the gap between genome instability and the reconfiguration of the tumour immune microenvironment, culminating in an enhanced response to ICI within the landscape of gastric cancer treatment. This all-encompassing review aims to dissect the potential of ARID1A as a valuable biomarker for immunotherapeutic approaches in gastric cancer, drawing from insights garnered from both preclinical experimentation and clinical observations.
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Affiliation(s)
- Xuemei Zhang
- Department of Oncology, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Youzhi Zhang
- Department of Oncology, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
- School of PharmacyHubei University of Science and TechnologyXianningChina
| | - Qiaoyun Zhang
- School of PharmacyHubei University of Science and TechnologyXianningChina
| | - Mengyao Lu
- Department of Oncology, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Yuan Chen
- Department of Oncology, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Xiaoyu Zhang
- Division of Gastrointestinal Surgery, Department of General Surgery, Huai'an Second People's Hospitalthe Affiliated Huai'an Hospital of Xuzhou Medical UniversityHuaianChina
| | - Peng Zhang
- Department of Oncology, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
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Li H, Shen M, Wang S. Current therapies and progress in the treatment of advanced gastric cancer. Front Oncol 2024; 14:1327055. [PMID: 38469246 PMCID: PMC10925707 DOI: 10.3389/fonc.2024.1327055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 02/05/2024] [Indexed: 03/13/2024] Open
Abstract
Gastric cancer (GC) remains one of the most life-threatening disease worldwide with poor prognosis because of the absence of effective treatment and the delay in diagnosis. Due to the delay of diagnosis, a large proportion of GC patients are diagnosed as advanced GC, with extreme short lifespan. In the past few years, some pivotal progress and novel therapies was proposed, and conducted into clinical researches and practice. In this study, we summarized the development of several novel immunotherapy or targeted treatment modalities for advanced GC, including immune checkpoint inhibitors, anti-angiogenic therapy and cancer vaccines. Additionally, the advantage and potential weakness in each of these therapeutic methods are also listed. Finally, we discussed the promising research direction of advanced GC treatment, and the limitation in basic and clinical research of advanced GC, including the combination of immunotherapy and targeted therapy.
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Affiliation(s)
- Hongyu Li
- Department of Gastroenterology, The People's Hospital Of Changxing Country, Zhejiang, China
| | - Ming Shen
- Department of Gastroenterology, The People's Hospital Of Changxing Country, Zhejiang, China
| | - Shihao Wang
- Department of Gastroenterology, The People's Hospital Of Changxing Country, Zhejiang, China
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12
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Ma C, Teng Q, Shang L, Du F, Li L. Tumor mutation load better predicts the prognosis of patients treated with immune checkpoint inhibitors in upper gastrointestinal cancers: A systematic review and meta-analysis. Cancer Rep (Hoboken) 2024; 7:e1959. [PMID: 38204354 PMCID: PMC10849990 DOI: 10.1002/cnr2.1959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 11/21/2023] [Accepted: 12/04/2023] [Indexed: 01/12/2024] Open
Abstract
BACKGROUND Tumor mutational load (TML) has emerged as a potential biomarker for multiple solid tumors. However, data on its prognostic impact on upper gastrointestinal (UGI) cancer are limited. Therefore, the aim of this systematic review and meta-analysis was to assess the prognostic value of TML for the survival of patients with UGI cancer. METHOD A comprehensive search of the PubMed, Embase, Cochrane Library, and Web of Science databases was conducted up to February 13, 2023. Eleven studies met our inclusion criteria. Hazard ratios (HRs) for progression-free survival and overall survival and their 95% confidence intervals (CIs) were calculated. Subsequently, the combined HR and its 95% CI were calculated for UGI tract cancers in the high and low TML groups. I2 statistics and p-values were used to evaluate heterogeneity. Publication bias, sensitivity, and subgroup analyses were performed to determine sources of heterogeneity. RESULTS In total, 932 patients with UGI tract cancer from 11 publications were included. The high TML group treated with immunotherapy showed significantly improved overall survival (HR = 0.68; 95% CI: 0.53, 0.86; p = .001) and progression-free survival (HR = 0.74; 95% CI: 0.58, 0.95; p = .020) compared with the low TML group. CONCLUSION Our study demonstrated that patients with UGI tumors and higher TML have a better prognosis with immunotherapy, suggesting that TML is a promising predictive biomarker for immunotherapy. REGISTRATION The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO Registration No: CRD42023405596).
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Affiliation(s)
- Chenghao Ma
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of MedicineShandong UniversityJinanChina
| | - Qiong Teng
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of MedicineShandong UniversityJinanChina
| | - Liang Shang
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of MedicineShandong UniversityJinanChina
- Department of Gastrointestinal SurgeryShandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanChina
| | - Fengying Du
- Department of Gastrointestinal SurgeryShandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanChina
| | - Leping Li
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of MedicineShandong UniversityJinanChina
- Department of Gastrointestinal SurgeryShandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanChina
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13
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Wei L, Wu X, Wang L, Chen L, Wu X, Song T, Wang Y, Chang W, Guo A, Niu Y, Huang H. Expression and prognostic value of APOBEC2 in gastric adenocarcinoma and its association with tumor-infiltrating immune cells. BMC Cancer 2024; 24:15. [PMID: 38166744 PMCID: PMC10763203 DOI: 10.1186/s12885-023-11769-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Accepted: 12/17/2023] [Indexed: 01/05/2024] Open
Abstract
BACKGROUND Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 2 (APOBEC2) is associated with nucleotide alterations in the transcripts of tumor-related genes which are contributed to carcinogenesis. Expression and prognosis value of APOBEC2 in stomach adenocarcinoma (STAD) remains unclear. METHODS The APOBEC2 gene alteration frequency of STAD and APOBEC2 gene expression in STAD and normal tissues were investigated in cBioportal and GEPIA, respectively. We detected expression of APOBEC2, infiltration of CD66b+ tumor-associated neutrophils and CD163+ tumor-associated macrophages in tissue microarrays by immunohistochemistry. APOBEC2 gene expression was explored by western blot and qRT-PCR. Relationships between APOBEC2 and CD66b, CD163, and other clinicopathological characteristics were investigated. Associations among APOBEC2 expression status and patient survival outcome were further analyzed. RESULTS APOBEC2 gene alteration frequency was 5%, and APOBEC2 gene was downexpressed in STAD compared to normal tissues (P < 0.05). APOBEC2 expression status were associated with the infiltration of CD66b+ TANs, differentiation grade, TNM stage, histological type and gender (all P < 0.05) in STAD. Little or no APOBEC2 expression was detected in STAD and adjacent normal tissues by western blot. We failed to show that APOBEC2 was an independent risk factor for OS (Hazard Ratio 0.816, 95%CI 0.574-1.161, P = 0.259) or DFS (Hazard Ratio 0.821, 95%CI 0.578-1.166, P = 0.270) in STAD by multivariate Cox regression analysis, but APOBEC2 negative subgroup has a worse OS and DFS among patients with adjuvant chemotherapy. CONCLUSIONS APOBEC2 correlates with CD66b, differentiation grade, TNM stages, histological classification, and gender in STAD. APOBEC2 is not an independent prognostic factor for STAD, our results suggest that patients with positive APOBEC2 can benefit from postoperative chemotherapy, and combination of APOBEC2 and CD66b is helpful to further stratify patients into different groups with distinct prognoses.
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Affiliation(s)
- Lipan Wei
- Department of Pathology, Second affiliated Hospital of Medical College of Shantou University, Shantou, China
| | - Xiuqian Wu
- Department of Interventional Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Lan Wang
- Department of Pathology, Second affiliated Hospital of Medical College of Shantou University, Shantou, China
| | - Ling Chen
- Department of Pharmacology, Shantou University Medical College, Shantou, China
| | - Xuejun Wu
- Department of Pharmacology, Shantou University Medical College, Shantou, China
| | - Tiantian Song
- Department of Pharmacology, Shantou University Medical College, Shantou, China
| | - Yuanyuan Wang
- Department of Pathology, Shantou Central Hospital, Shantou, China
| | - Wenjun Chang
- Department of Environmental Hygiene, Second Military Medical University, Shanghai, China
| | - Aizhen Guo
- Department of General Practice, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, China.
| | - Yongdong Niu
- Department of Pharmacology, Shantou University Medical College, Shantou, China.
| | - Haihua Huang
- Department of Pathology, Second affiliated Hospital of Medical College of Shantou University, Shantou, China.
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14
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Zhang D, Sun R, Di C, Li L, Zhao F, Han Y, Zhang W. Microdissection of cancer-associated fibroblast infiltration subtypes unveils the secreted SERPINE2 contributing to immunosuppressive microenvironment and immuotherapeutic resistance in gastric cancer: A large-scale study integrating bulk and single-cell transcriptome profiling. Comput Biol Med 2023; 166:107406. [PMID: 37729702 DOI: 10.1016/j.compbiomed.2023.107406] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 07/23/2023] [Accepted: 08/26/2023] [Indexed: 09/22/2023]
Abstract
In the era of immunotherapy, the suboptimal response rate and the development of acquired resistance among the initial beneficiaries continue to present significant challenges across multiple malignancies, including gastric cancer (GC). Considering that the interactions of tumor stroma, especially the cancer-associated fibroblasts (CAFs), with immune and tumor cells, play indispensable roles in tumor progression, tumor microenvironment remodeling and therapeutic responsiveness, in-depth exploration on the roles of CAFs and pivotal mediators of their functions may provide novel clues to increase the effectiveness of current immunotherapeutic drugs and further achieve synergistic antitumor response. Herein, through the consensus clustering of canonical biomarkers, three GC subclasses with different abundance of CAFs were virtually microdissected in four integrated bulk cohorts encompassing 2148 GC patients from 11 independent datasets. An extensive immunogenomic analysis revealed that tumors with high CAFs infiltration were characterized with unfavorable outcomes, aggressive phenotypes, decreased tumor immunogenicity, high risk of immune evasion and thus immunotherapeutic resistance. By leveraging large-scale single-cell transcriptomic profiling, a series of CAF-secreted proteins were identified, among which the SERPINE2 was confirmed to be restrictively enriched in stromal fibroblasts of GC tissues and contribute to promoting a protumor milieu and fostering an immunosuppressive microenvironment via bioinformatics computations and tissue microarray analysis. Moreover, pan-cancer investigations generalized the immunological roles of SERPINE2, especially in pan-gastrointestinal malignancies, with multiple real-world immunotherapy cohorts further confirming its implications on predicting immunotherapeutic efficacy. In conclusion, these findings suggest that the CAF-derived SERPINE2 is a promising immune-oncology target with therapeutic implications to further synergize the immunotherapeutic combinations.
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Affiliation(s)
- Dong Zhang
- Department of Breast and Thyroid Surgery, General Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; Department of Breast and Thyroid Surgery, General Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, China; Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China; Department of Clinical Medicine, The First Clinical College, Shandong University, Jinan, Shandong, 250012, China.
| | - Rui Sun
- Department of Clinical Medicine, The First Clinical College, Shandong University, Jinan, Shandong, 250012, China; Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China
| | - Chenyu Di
- Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China; Department of Clinical Medicine, The First Clinical College, Shandong University, Jinan, Shandong, 250012, China
| | - Lin Li
- Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, 250000, China
| | - Faming Zhao
- Key Laboratory of Environmental Health, Ministry of Education & Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yu Han
- Department of Pathology, Shengli Oilfield Central Hospital, Dongying, Shandong, 257000, China
| | - Wenjie Zhang
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, 250011, China; Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250011, China.
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Lewis CR, Dadgar N, Yellin SA, Donnenberg VS, Donnenberg AD, Bartlett DL, Allen CJ, Wagner PL. Regional Immunotherapy for Peritoneal Carcinomatosis in Gastroesophageal Cancer: Emerging Strategies to Re-Condition a Maladaptive Tumor Environment. Cancers (Basel) 2023; 15:5107. [PMID: 37894473 PMCID: PMC10605802 DOI: 10.3390/cancers15205107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 10/04/2023] [Accepted: 10/20/2023] [Indexed: 10/29/2023] Open
Abstract
Peritoneal carcinomatosis originating from gastric/gastroesophageal junction cancer (GC-PC) occurs in a defined subset of gastric cancer patients with unique clinical, pathologic, molecular and immunologic characteristics that create significant obstacles to effective treatment with modern therapy. Although systemic chemo- and immuno- therapy have yielded disappointing results in GC-PC, recent advances in the characterization of GC-PC and peritoneal immune biology present new opportunities for targeted therapeutics. In this review article, we discuss the distinct properties of GC-PC and the peritoneal immune environment as they pertain to current and investigative treatment strategies. We discuss pre-clinical studies and clinical trials relevant to the modulation of the peritoneal environment as a therapeutic intervention in GC-PC. Finally, we present a road map for future combinatorial strategies based on the conception of the peritoneal cavity as a bioreactor. Within this isolated compartment, prevailing immunosuppressive conditions can be altered through regional interventions toward an adaptive phenotype that would support the effectiveness of regionally delivered cellular therapy products. It is hoped that novel combination strategies would promote efficacy not only in the sequestered peritoneal environment, but also via migration into the circulation of tumor-reactive lymphocytes to produce durable systemic disease control, thereby improving oncologic outcome and quality of life in patients with GC-PC.
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Affiliation(s)
- Catherine R. Lewis
- Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA; (C.R.L.); (A.D.D.); (D.L.B.); (C.J.A.)
| | - Neda Dadgar
- Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA;
| | - Samuel A. Yellin
- Department of Surgery, Lehigh Valley Health Network, Allentown, PA 18101, USA;
| | - Vera S. Donnenberg
- Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA;
- Hillman Cancer Centers, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
| | - Albert D. Donnenberg
- Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA; (C.R.L.); (A.D.D.); (D.L.B.); (C.J.A.)
| | - David L. Bartlett
- Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA; (C.R.L.); (A.D.D.); (D.L.B.); (C.J.A.)
| | - Casey J. Allen
- Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA; (C.R.L.); (A.D.D.); (D.L.B.); (C.J.A.)
| | - Patrick L. Wagner
- Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA; (C.R.L.); (A.D.D.); (D.L.B.); (C.J.A.)
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16
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Gu X, Shen H, Zhu G, Li X, Zhang Y, Zhang R, Su F, Wang Z. Prognostic Model and Tumor Immune Microenvironment Analysis of Complement-Related Genes in Gastric Cancer. J Inflamm Res 2023; 16:4697-4711. [PMID: 37872955 PMCID: PMC10590588 DOI: 10.2147/jir.s422903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 10/12/2023] [Indexed: 10/25/2023] Open
Abstract
Introduction The complement system is integral to the innate and adaptive immune response, helping antibodies eliminate pathogens. However, the potential role of complement and its modulators in the tumor microenvironment (TME) of gastric cancer (GC) remains unclear. Methods This study assessed the expression, frequency of somatic mutations, and copy number variations of complement family genes in GC derived from The Cancer Genome Atlas (TCGA). Lasso and Cox regression analyses were conducted to develop a prognostic model based on the complement genes family, with the training and validation sets taken from the TCGA-GC cohort (n=371) and the International Gene Expression Omnibus (GEO) cohort (n=433), correspondingly. The nomogram assessment model was used to predict patient outcomes. Additionally, the link between immune checkpoints, immune cells, and the prognostic model was investigated. Results In contrast to patients at low risk, those at high risk had a less favorable outcome. The prognostic model-derived risk score was shown to serve as a prognostic marker of GC independently, as per the multivariate Cox analysis. Nomogram assessment showed that the model had high reliability for predicting the survival of patients with GC in the 1, 3, 5 years. Additionally, the risk score was positively linked to the expression of immune checkpoints, notably CTLA4, LAG3, PDCD1, and CD274, according to an analysis of immune processes. The core gene C5aR1 in the prognostic model was found to be upregulated in GC tissues in contrast to adjoining normal tissues, and patients with elevated expressed levels of C5aR1 had lower 10-year overall survival (OS) rates. Conclusion Our work reveals that complement genes are associated with the diversity and complexity of TME. The complement prognosis model help improves our understanding of TME infiltration characteristics and makes immunotherapeutic strategies more effective.
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Affiliation(s)
- Xianhua Gu
- Department of Gynecology Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China
| | - Honghong Shen
- Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China
| | - Guangzheng Zhu
- Department of Surgical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China
| | - Xinwei Li
- Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China
| | - Yue Zhang
- Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China
| | - Rong Zhang
- Department of Gynecology Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China
| | - Fang Su
- Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China
| | - Zishu Wang
- Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China
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17
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Pan Y, Ma Y, Dai G. The Prognostic Value of the Prognostic Nutritional Index in Patients with Advanced or Metastatic Gastric Cancer Treated with Immunotherapy. Nutrients 2023; 15:4290. [PMID: 37836573 PMCID: PMC10574242 DOI: 10.3390/nu15194290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 09/25/2023] [Accepted: 10/06/2023] [Indexed: 10/15/2023] Open
Abstract
In recent years, the therapeutic effect of monoclonal antibodies against programmed cell death protein-1 (PD-1) in patients with locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) cancer has been confirmed in many studies. The exploration and discovery of new biomarker combinations based on tumor characteristics and tumor microenvironment help screen superior patients and realize precise immunotherapy. As an evaluation index of immunonutritional status, the prognostic nutritional index (PNI) is low cost, simple and easy to obtain, and effective in determining the prognosis of tumor patients. We selected 268 consecutive AGC patients who were treated with ICI therapy from December 2014 to May 2021. We measured their pretreatment of the PNI levels and performed univariate and multivariate Cox regression analyses of progression-free survival (PFS) or overall survival (OS) after ICI therapy. The low pretreatment PNI level of AGC patients was significantly correlated with shorter PFS (p < 0.001) and OS (p < 0.001) after ICI treatment. In univariate and multivariate analyses of the associations between PNI and OS or PFS, PNI is an independent prognostic factor for PFS (HR = 1.511; 95%CI 1.154-1.977; p = 0.003) and OS (HR = 1.431; 95%CI 1.049-1.951; p = 0.024), respectively. Notably, decreased PNI during treatment with ICIs was associated with early relapse and death. Pretreatment with PNI might help to identify AGC patients who will obtain a survival benefit from ICI therapy.
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Affiliation(s)
- Yuting Pan
- Chinese PLA Medical School, Beijing 100853, China; (Y.P.); (Y.M.)
- Medical Oncology Department, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100853, China
| | - Yue Ma
- Chinese PLA Medical School, Beijing 100853, China; (Y.P.); (Y.M.)
- Medical Oncology Department, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100853, China
| | - Guanghai Dai
- Chinese PLA Medical School, Beijing 100853, China; (Y.P.); (Y.M.)
- Medical Oncology Department, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100853, China
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18
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Lu M, Wu Y, Zhang Y, Yu Y, Wang S, Su X. Immunotherapeutic strategy in the management of gastric cancer: molecular profiles, current practice, and ongoing trials. J Egypt Natl Canc Inst 2023; 35:32. [PMID: 37779128 DOI: 10.1186/s43046-023-00192-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Accepted: 09/15/2023] [Indexed: 10/03/2023] Open
Abstract
Gastric cancer (GC) is the one of the most commonly solid cancer worldwide. Although under the aggressive treatment, the poor clinical outcomes of patients with GCs have not been improved. Current studies emphasized that targeting therapies or immune response-based therapeutic strategy may be a potential approach to improve the clinical outcomes. Moreover, accumulative evidence has reported the increasing expression of PD-L1 expression in GC cells and highlighted its role in the tumor progression. Currently, great development has been established in the immune checkpoint inhibitors (ICIs) and further changed the clinical practice of GC treatment and prognosis. In addition, the combination therapies with targeting therapy or traditional therapies are expected to push the development of immunotherapies. In our present review, we predominantly focus on the biomarkers and molecular profiles for immunotherapies in GCs and highlight the role and administration of ICIs-based immunotherapeutic strategies against the GCs.
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Affiliation(s)
- Mengxiao Lu
- Department of Gastrointestinal Minimally Invasive Surgery, The Affiliated People's Hospital of Ningbo University, Ningbo, China.
| | - Yingjie Wu
- Department of Gastrointestinal Minimally Invasive Surgery, The Affiliated People's Hospital of Ningbo University, Ningbo, China
| | - Yixin Zhang
- Department of Gastrointestinal Minimally Invasive Surgery, The Affiliated People's Hospital of Ningbo University, Ningbo, China
| | - Yu Yu
- Department of Gastrointestinal Minimally Invasive Surgery, The Affiliated People's Hospital of Ningbo University, Ningbo, China
| | | | - Xiaobao Su
- Department of Gastrointestinal Minimally Invasive Surgery, The Affiliated People's Hospital of Ningbo University, Ningbo, China
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Suga T, Kimura Y, Furuya K, Sato H. Hepatocellular carcinoma with gastric adenocarcinoma treated with atezolizumab and bevacizumab. Clin Case Rep 2023; 11:e7875. [PMID: 37692146 PMCID: PMC10483490 DOI: 10.1002/ccr3.7875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 08/19/2023] [Indexed: 09/12/2023] Open
Abstract
Atezolizumab and bevacizumab combination therapy might be one of the treatment options for hepatocellular carcinoma concurrent with gastric adenocarcinoma.
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Affiliation(s)
- Takayoshi Suga
- Department of GastroenterologyShibukawa Medical Center, National Hospital OrganizationShibukawaGunmaJapan
- Department of Gastroenterology and HepatologyGunma University Graduate School of MedicineMaebashiGunmaJapan
| | - Yuko Kimura
- Department of GastroenterologyShibukawa Medical Center, National Hospital OrganizationShibukawaGunmaJapan
- Department of Gastroenterology and HepatologyGunma University Graduate School of MedicineMaebashiGunmaJapan
| | - Kensuke Furuya
- Department of GastroenterologyShibukawa Medical Center, National Hospital OrganizationShibukawaGunmaJapan
- Department of Gastroenterology and HepatologyGunma University Graduate School of MedicineMaebashiGunmaJapan
| | - Hiroko Sato
- Department of GastroenterologyShibukawa Medical Center, National Hospital OrganizationShibukawaGunmaJapan
- Department of Gastroenterology and HepatologyGunma University Graduate School of MedicineMaebashiGunmaJapan
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20
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Qing X, Jiang J, Yuan C, Xie K, Wang K. Expression patterns and immunological characterization of PANoptosis -related genes in gastric cancer. Front Endocrinol (Lausanne) 2023; 14:1222072. [PMID: 37664853 PMCID: PMC10471966 DOI: 10.3389/fendo.2023.1222072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Accepted: 08/03/2023] [Indexed: 09/05/2023] Open
Abstract
Background Accumulative studies have demonstrated the close relationship between tumor immunity and pyroptosis, apoptosis, and necroptosis. However, the role of PANoptosis in gastric cancer (GC) is yet to be fully understood. Methods This research attempted to identify the expression patterns of PANoptosis regulators and the immune landscape in GC by integrating the GSE54129 and GSE65801 datasets. We analyzed GC specimens and established molecular clusters associated with PANoptosis-related genes (PRGs) and corresponding immune characteristics. The differentially expressed genes were determined with the WGCNA method. Afterward, we employed four machine learning algorithms (Random Forest, Support Vector Machine, Generalized linear Model, and eXtreme Gradient Boosting) to select the optimal model, which was validated using nomogram, calibration curve, decision curve analysis (DCA), and two validation cohorts. Additionally, this study discussed the relationship between infiltrating immune cells and variables in the selected model. Results This study identified dysregulated PRGs and differential immune activities between GC and normal samples, and further identified two PANoptosis-related molecular clusters in GC. These clusters demonstrated remarkable immunological heterogeneity, with Cluster1 exhibiting abundant immune infiltration. The Support Vector Machine signature was found to have the best discriminative ability, and a 5-gene-based SVM signature was established. This model showed excellent performance in the external validation cohorts, and the nomogram, calibration curve, and DCA indicated its reliability in predicting GC patterns. Further analysis confirmed that the 5 selected variables were remarkably related to infiltrating immune cells and immune-related pathways. Conclusion Taken together, this work demonstrates that the PANoptosis pattern has the potential as a stratification tool for patient risk assessment and a reflection of the immune microenvironment in GC.
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Affiliation(s)
- Xin Qing
- Clinical Laboratory, Boai Hospital of Zhongshan Affiliated to Southern Medical University, Zhongshan, China
- West China Hospital, Sichuan University, Chengdu, China
| | - Junyi Jiang
- Clinical Laboratory, Boai Hospital of Zhongshan Affiliated to Southern Medical University, Zhongshan, China
| | - Chunlei Yuan
- Clinical Laboratory, Boai Hospital of Zhongshan Affiliated to Southern Medical University, Zhongshan, China
| | - Kunke Xie
- Clinical Laboratory, Boai Hospital of Zhongshan Affiliated to Southern Medical University, Zhongshan, China
| | - Ke Wang
- Clinical Laboratory, Boai Hospital of Zhongshan Affiliated to Southern Medical University, Zhongshan, China
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21
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Chen Y, Chen S, Zhu J, Yang S, Yu Q, Xu S. PRKAA1 predicts prognosis and is associated with immune characteristics in gastric cancer. Funct Integr Genomics 2023; 23:252. [PMID: 37482545 DOI: 10.1007/s10142-023-01176-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 07/10/2023] [Accepted: 07/12/2023] [Indexed: 07/25/2023]
Abstract
PRKAA1 is the α-subunit of 5-AMP-activated protein kinase. This study aimed to investigate the role of PRKAA1 expression with multiple clinical parameters, the overall survival rate, blood indexes, and immune infiltration in gastric cancer (GC) patients. We investigated PRKAA1 expression data in GC patients using ELISA, protein atlas, UALCAN, and GEPIA. PRKAA1 expression was associated with immune cell infiltration, and immune cell types were analyzed with the TIMER, DICE, and protein atlas databases. We compared the level of PRKAA1 expression based on the clinical features of GC patients (n = 345). GC patients were divided into two groups based on PRKAA1 expression, and the lymphocyte subsets, overall survival rate, and clinical parameters were compared with peripheral blood mononuclear cell and biochemical indexes. PRKAA1 was highly expressed in the serum of GC patients compared with that of healthy individuals. GC patients with distant metastases, a later TNM stage, and stage IV in UICC exhibited higher PRKAA1 expression. PRKAA1 expression was significantly correlated with circulating T cells. The protein atlas and DICE database results confirmed that PRKAA1 was closely associated with T cells in a single-cell cluster. Furthermore, GC patients with low PRKAA1 expression had better OS rates. PRKAA1 may serve as a potential prognostic biomarker for GC and have an association with immune infiltrates.
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Affiliation(s)
- Yongyi Chen
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
- The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
| | - Siyu Chen
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
- The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
| | - Jing Zhu
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
- The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
| | - Shaoxue Yang
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
- The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
| | - Qiong Yu
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
- The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
| | - Songxiao Xu
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China.
- The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China.
- Department of Clinical Laboratory, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, 310022, China.
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22
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Fu Y, Wang B, Fu P, Zhang L, Bao Y, Gao ZZ. Delineation of fatty acid metabolism in gastric cancer: Therapeutic implications. World J Clin Cases 2023; 11:4800-4813. [PMID: 37583992 PMCID: PMC10424035 DOI: 10.12998/wjcc.v11.i20.4800] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 04/23/2023] [Accepted: 05/19/2023] [Indexed: 07/11/2023] Open
Abstract
BACKGROUND The prognosis of gastric cancer is extremely poor. Metabolic reprogramming involving lipids has been associated with cancer occurrence and progression. AIM To illustrate fatty acid metabolic mechanisms in gastric cancer, detect core genes, develop a prognostic model, and provide treatment options. METHODS Raw data from The Cancer Genome Atlas and Gene Expression Omnibus databases were collected and analyzed. Differentially expressed fatty acid metabolism genes were identified and incorporated into a risk model based on least absolute shrinkage and selection operator regression analysis. Then, patients from The Cancer Genome Atlas were assigned to high- and low-risk cohorts according to the mean value of the risk score as the threshold, which was verified in the Gene Expression Omnibus database. Relationships between chemotherapeutic sensitivity and tumor microenvironment features were assessed. RESULTS An integrated evaluation was performed in this study. Fatty acid metabolism-related genes were used to construct the risk model. Patients classified into the high-risk cohort were considered to be resistant to chemotherapy based on results of the "pRRophetic" R package. Patients in the high-risk cohort were associated with type I/II interferon activation, increased inflammation level, immune cell infiltration, and tumor immune dysfunction based on the exclusion algorithm, indicating the potential benefit of immunotherapy in these patients. CONCLUSION We constructed a fatty acid-related risk score model to assess the comprehensive fatty acid features in gastric cancer and validated its vital role in prognosis, chemotherapy sensitivity, and immunotherapy.
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Affiliation(s)
- Yu Fu
- Department of General Practice Medicine, The Second affiliated hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
| | - Bin Wang
- Department of General Practice Medicine, The Second affiliated hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
| | - Peng Fu
- Department of Orthopeadic Oncology, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
| | - Lei Zhang
- Department of Clinical Oncology, The Second affiliated hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
| | - Yi Bao
- Department of Clinical Oncology, The Second affiliated hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
| | - Zhen-Zhen Gao
- Department of Clinical Oncology, The Second affiliated hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
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23
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Fu Y, Wang B, Fu P, Zhang L, Bao Y, Gao ZZ. Delineation of fatty acid metabolism in gastric cancer: Therapeutic implications. World J Clin Cases 2023; 11:4796-4809. [DOI: 10.12998/wjcc.v11.i20.4796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 04/23/2023] [Accepted: 05/19/2023] [Indexed: 07/06/2023] Open
Abstract
BACKGROUND The prognosis of gastric cancer is extremely poor. Metabolic reprogramming involving lipids has been associated with cancer occurrence and progression.
AIM To illustrate fatty acid metabolic mechanisms in gastric cancer, detect core genes, develop a prognostic model, and provide treatment options.
METHODS Raw data from The Cancer Genome Atlas and Gene Expression Omnibus databases were collected and analyzed. Differentially expressed fatty acid metabolism genes were identified and incorporated into a risk model based on least absolute shrinkage and selection operator regression analysis. Then, patients from The Cancer Genome Atlas were assigned to high- and low-risk cohorts according to the mean value of the risk score as the threshold, which was verified in the Gene Expression Omnibus database. Relationships between chemotherapeutic sensitivity and tumor microenvironment features were assessed.
RESULTS An integrated evaluation was performed in this study. Fatty acid metabolism-related genes were used to construct the risk model. Patients classified into the high-risk cohort were considered to be resistant to chemotherapy based on results of the “pRRophetic” R package. Patients in the high-risk cohort were associated with type I/II interferon activation, increased inflammation level, immune cell infiltration, and tumor immune dysfunction based on the exclusion algorithm, indicating the potential benefit of immunotherapy in these patients.
CONCLUSION We constructed a fatty acid-related risk score model to assess the comprehensive fatty acid features in gastric cancer and validated its vital role in prognosis, chemotherapy sensitivity, and immunotherapy.
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Affiliation(s)
- Yu Fu
- Department of General Practice Medicine, The Second affiliated hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
| | - Bin Wang
- Department of General Practice Medicine, The Second affiliated hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
| | - Peng Fu
- Department of Orthopeadic Oncology, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
| | - Lei Zhang
- Department of Clinical Oncology, The Second affiliated hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
| | - Yi Bao
- Department of Clinical Oncology, The Second affiliated hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
| | - Zhen-Zhen Gao
- Department of Clinical Oncology, The Second affiliated hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
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Ma X, Jia S, Wang G, Liang M, Guo T, Du H, Li S, Li X, Huangfu L, Guo J, Xing X, Ji J. TRIM28 promotes the escape of gastric cancer cells from immune surveillance by increasing PD-L1 abundance. Signal Transduct Target Ther 2023; 8:246. [PMID: 37357254 DOI: 10.1038/s41392-023-01450-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2022] [Revised: 04/06/2023] [Accepted: 04/25/2023] [Indexed: 06/27/2023] Open
Abstract
Immune checkpoint blockade (ICB) offers a new opportunity for treatment for gastric cancer (G.C.). Understanding the upstream regulation of immune checkpoints is crucial to further improve the efficacy of ICB therapy. Herein, using the CRISPR-Cas9-based genome-wide screening, we identified TRIM28 as one of the most significant regulators of PD-L1, a checkpoint protein, in G.C. cells. Mechanistically, TRIM28 directly binds to and stabilizes PD-L1 by inhibiting PD-L1 ubiquitination and promoting PD-L1 SUMOylation. Furthermore, TRIM28 facilitates K63 polyubiquitination of TBK1, activating TBK1-IRF1 and TBK1-mTOR pathways, resulting in enhanced PD-L1 transcription. It was found that TRIM28 was positively correlated with PD-L1 in G.C. cells. Moreover, high TRIM28 expression suggests poor survival in a cohort of 466 patients with G.C., and this observation is consistent while analyzing data from publicly available databases. Ectopic TRIM28 expression facilitated tumor growth, increased PD-L1 expression, and suppressed T cell activation in mice. Administration of the PD-L1 or TBK1 inhibitor significantly alleviated the TRIM28-induced tumor progression. Furthermore, combining the TBK1 inhibitor with CTLA4 immune checkpoint blockade has synergistic effects on G.C., and provides a novel strategy for G.C. therapy.
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Affiliation(s)
- Xiaoxiao Ma
- Department of Gastrointestinal Cancer Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
- Department of Molecular Diagnostics, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Shuqin Jia
- Department of Molecular Diagnostics, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Gangjian Wang
- Department of Gastrointestinal Cancer Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Min Liang
- Department of Molecular Diagnostics, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Ting Guo
- Department of Gastrointestinal Cancer Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Hong Du
- Department of Gastrointestinal Cancer Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Sisi Li
- Department of Molecular Diagnostics, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Xiaomei Li
- Department of Gastrointestinal Cancer Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Longtao Huangfu
- Department of Gastrointestinal Cancer Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Jianping Guo
- Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510275, China.
| | - Xiaofang Xing
- Department of Gastrointestinal Cancer Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
| | - Jiafu Ji
- Department of Gastrointestinal Cancer Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
- Department of Molecular Diagnostics, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
- Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
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Leowattana W, Leowattana P, Leowattana T. Immunotherapy for advanced gastric cancer. World J Methodol 2023; 13:79-97. [PMID: 37456977 PMCID: PMC10348086 DOI: 10.5662/wjm.v13.i3.79] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 05/11/2023] [Accepted: 05/31/2023] [Indexed: 06/20/2023] Open
Abstract
Gastric cancer (GC) is believed to be the fifth most common cancer and the third most common cause of death worldwide. Treatment techniques include radiation, chemotherapy, gastrectomy, and targeted treatments are often employed. Some hopeful results from the development of GC immunotherapy have already changed treatment approaches. Along with previous combination medicines, new immunotherapies have been developed that target distinct molecules. Despite ongoing studies into the current therapeutic options and significant improvements in this field, the prognosis for the ailment is poor. Since there are few treatment options and a delay in detection, the illness actually advances, spreads, and metastasizes. The bulk of immunotherapies in use today rely on cytotoxic immune cells, monoclonal antibodies, and gene-transferred vaccines. Immune checkpoint inhibitors have become more popular. In this review, we sought to examine the viewpoint and development of several immunotherapy treatment modalities for advanced GC, as well as the clinical results thus far reported. Additionally, we outlined tumor immune escape and tumor immunosurveillance.
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Affiliation(s)
- Wattana Leowattana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Rachatawee 10400, Bangkok, Thailand
| | - Pathomthep Leowattana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Rachatawee 10400, Bangkok, Thailand
| | - Tawithep Leowattana
- Department of Medicine, Faculty of Medicine, Srinakharinwirot University, Wattana 10110, Bangkok, Thailand
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Huang H, Li Z, Xia Y, Zhao Z, Wang D, Jin H, Liu F, Yang Y, Shen L, Lu Z. Association between radiomics features of DCE-MRI and CD8 + and CD4 + TILs in advanced gastric cancer. Pathol Oncol Res 2023; 29:1611001. [PMID: 37342362 PMCID: PMC10277864 DOI: 10.3389/pore.2023.1611001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 05/24/2023] [Indexed: 06/22/2023]
Abstract
Objective: The aim of this investigation was to explore the correlation between the levels of tumor-infiltrating CD8+ and CD4+ T cells and the quantitative pharmacokinetic parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced gastric cancer. Methods: We retrospectively analyzed the data of 103 patients with histopathologically confirmed advanced gastric cancer (AGC). Three pharmacokinetic parameters, Kep, Ktrans, and Ve, and their radiomics characteristics were obtained by Omni Kinetics software. Immunohistochemical staining was used to determine CD4+ and CD8+ TILs. Statistical analysis was subsequently performed to assess the correlation between radiomics characteristics and CD4+ and CD8+ TIL density. Results: All patients included in this study were finally divided into either a CD8+ TILs low-density group (n = 51) (CD8+ TILs < 138) or a high-density group (n = 52) (CD8+ TILs ≥ 138), and a CD4+ TILs low-density group (n = 51) (CD4+ TILs < 87) or a high-density group (n = 52) (CD4+ TILs ≥ 87). ClusterShade and Skewness based on Kep and Skewness based on Ktrans both showed moderate negative correlation with CD8+ TIL levels (r = 0.630-0.349, p < 0.001), with ClusterShade based on Kep having the highest negative correlation (r = -0.630, p < 0.001). Inertia-based Kep showed a moderate positive correlation with the CD4+ TIL level (r = 0.549, p < 0.001), and the Correlation based on Kep showed a moderate negative correlation with the CD4+ TIL level, which also had the highest correlation coefficient (r = -0.616, p < 0.001). The diagnostic efficacy of the above features was assessed by ROC curves. For CD8+ TILs, ClusterShade of Kep had the highest mean area under the curve (AUC) (0.863). For CD4+ TILs, the Correlation of Kep had the highest mean AUC (0.856). Conclusion: The radiomics features of DCE-MRI are associated with the expression of tumor-infiltrating CD8+ and CD4+ T cells in AGC, which have the potential to noninvasively evaluate the expression of CD8+ and CD4+ TILs in AGC patients.
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Affiliation(s)
- Huizhen Huang
- Shaoxing of Medicine, Shaoxing University, Shaoxing, China
| | - Zhiheng Li
- Department of Radiology, Anhui Provincial Hospital, Hefei, China
| | - Yue Xia
- Shaoxing of Medicine, Shaoxing University, Shaoxing, China
| | - Zhenhua Zhao
- Department of Radiology, Shaoxing People’s Hospital, Shaoxing, China
| | - Dandan Wang
- Department of Radiology, Shaoxing People’s Hospital, Shaoxing, China
| | - Hongyan Jin
- Country Department of Pathology, Shaoxing People’s Hospital, Shaoxing, China
| | - Fang Liu
- Country Department of Pathology, Shaoxing People’s Hospital, Shaoxing, China
| | - Ye Yang
- Country Department of Pathology, Shaoxing People’s Hospital, Shaoxing, China
| | - Liyijing Shen
- Department of Radiology, Shaoxing People’s Hospital, Shaoxing, China
| | - Zengxin Lu
- Department of Radiology, Shaoxing People’s Hospital, Shaoxing, China
- The First Affiliated Hospital of Shaoxing University, Shaoxing, China
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Gu X, Shen H, Xiang Z, Li X, Zhang Y, Zhang R, Su F, Wang Z. Exploring the Correlation Between GPR176, a Potential Target Gene of Gastric Cancer, and Immune Cell Infiltration. Pharmgenomics Pers Med 2023; 16:519-535. [PMID: 37284492 PMCID: PMC10241216 DOI: 10.2147/pgpm.s411199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Accepted: 05/26/2023] [Indexed: 06/08/2023] Open
Abstract
Introduction GPR176, an orphan G protein-coupled receptor (GPCR), is essential for the progression of gastrointestinal cancers. However, it is still unclear how GPR176 affects tumor immunity and patient prognosis in gastric cancer (GC). Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were searched in this investigation to assess the expression patterns of GPR176 in GC tissues and normal gastric mucosa. The findings were further verified using immunohistochemical tests and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). The Kaplan-Meier method, univariate logistic regression, and Cox regression were then used to investigate the relationship between GPR176 and clinical traits. Additionally, the potential correlation between GPR176, immune checkpoint genes, and immune cell infiltration levels was investigated. Results As per the research findings, GC tissues had higher levels of GPR176 than normal tissues. Additionally, individuals with high expression of GPR176 had a worse 10-year overall survival (OS), in contrast with those having a low expression of GPR176 (p < 0.001). The OS of GC can be predicted using a validated nomogram model. The expression of GPR176 demonstrated a negative correlation with CD8+ T cells. When compared to the low-expression group of GPR176, Tumor Immune Dysfunction and Exclusion (TIDE) analysis demonstrated that the high-expression group had a considerably higher risk of immune evasion. A remarkable difference (variation) was observed in the levels of GPR176 expression across both groups, ie, low and high-risk groups, as determined by the immune phenomenon scores (IPS) immunotherapy assessment. Conclusion By examining GPR176 from various biological perspectives, it was determined that GPR176 can act as a predictive biomarker for poor patient prognosis in GC. Additionally, it was observed that GPR176 is capable of suppressing the proliferation of CD8+ T cells and facilitating immune evasion.
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Affiliation(s)
- Xianhua Gu
- Department of Gynecology Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China
| | - Honghong Shen
- Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China
| | - Zheng Xiang
- Department of Surgical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China
| | - Xinwei Li
- Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China
| | - Yue Zhang
- Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China
| | - Rong Zhang
- Department of Gynecology Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China
| | - Fang Su
- Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China
| | - Zishu Wang
- Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China
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Guo SB, Du S, Cai KY, Cai HJ, Huang WJ, Tian XP. A scientometrics and visualization analysis of oxidative stress modulator Nrf2 in cancer profiles its characteristics and reveals its association with immune response. Heliyon 2023; 9:e17075. [PMID: 37342570 PMCID: PMC10277599 DOI: 10.1016/j.heliyon.2023.e17075] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 06/02/2023] [Accepted: 06/06/2023] [Indexed: 06/23/2023] Open
Abstract
Background Nrf2, an essential and fascinating transcription factor, enjoys a dual property in the occurrence and development of inflammation and cancer. For over two decades, numerous studies regarding Nrf2 in cancer have been reported, whereas there is still a lack of a scientometrics and visualization analysis of Nrf2 in cancer. Hence, a scientometric study regarding the oxidative stress modulator Nrf2 was implemented. Methods After the quality screening, we defined 7168 relevant studies from 2000 to 2021. CiteSpace, VOSviewer, R software, and GraphPad Prism were used for the following scientometric study and visualization analysis, including field profiles, research hotspots, and future predictions. Results The total number of publications and citations are 1058 and 54,690, respectively. After polynomial fitting curve analysis, two prediction functions of the annual publication number (y = 3.3909x2 - 13585x + 1 E+07) and citation number (185.45x2 - 743669x + 7 E+08) were generated. After scientometric analysis, we found that Biochemistry Molecular Biology correlates with Nrf2 in cancer highly, and Free Radical Biology and Medicine is a good choice for submitting Nrf2-related manuscripts. The current research hotspots of Nrf2 in cancer mainly focus on cancer therapy and its cellular and molecular mechanisms. "antioxidant response element (87.5)", "gene expression (43.98)", "antioxidant responsive element (21.14)", "chemoprevention (20.05)", "carcinogenesis (19.2)", "cancer chemoprevention (18.45)", "free radical (17.15)", "response element (14.17)", and "chemopreventive agent (14.04)" are important for cancer therapy study. In addition, "glutathione-S-transferase (47)", "keap1 (15.39)", and "heme oxygenase 1 gene (24.35)" are important for inflammation and cell fate study. More interestingly, by performing an "InfoMap" algorithm, the thematic map showed that the "immune response" is essential to oxidative stress modulator Nrf2 but not well developed, indicating it deserves further exploration. Conclusion This study revealed field profiles, research hotspots, and future directions of oxidative stress modulator Nrf2 in inflammation and cancer research, and our findings will offer a vigorous roadmap for further studies in this field.
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Affiliation(s)
- Song-Bin Guo
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China
| | - Sheng Du
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, PR China
| | - Ke-Yu Cai
- Department of Colorectal and Anal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, PR China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, PR China
| | - Han-Jia Cai
- The Second Clinical Medical College, Guangzhou Medical University, Guangzhou, 511436, PR China
| | - Wei-Juan Huang
- Department of Pharmacology, College of Pharmacy, Jinan University, Guangzhou, 510632, PR China
| | - Xiao-Peng Tian
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China
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Wang X, Zhang C, Song H, Yuan J, Zhang X, Yuan Y, Zhang L, He J. Characterization of LIMA1 and its emerging roles and potential therapeutic prospects in cancers. Front Oncol 2023; 13:1115943. [PMID: 37274282 PMCID: PMC10235525 DOI: 10.3389/fonc.2023.1115943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Accepted: 05/02/2023] [Indexed: 06/06/2023] Open
Abstract
Actin is the most abundant and highly conserved cytoskeletal protein present in all eukaryotic cells. Remodeling of the actin cytoskeleton is controlled by a variety of actin-binding proteins that are extensively involved in biological processes such as cell motility and maintenance of cell shape. LIM domain and actin-binding protein 1 (LIMA1), as an important actin cytoskeletal regulator, was initially thought to be a tumor suppressor frequently downregulated in epithelial tumors. Importantly, the deficiency of LIMA1 may be responsible for dysregulated cytoskeletal dynamics, altered cell motility and disrupted cell-cell adhesion, which promote tumor proliferation, invasion and migration. As research progresses, the roles of LIMA1 extend from cytoskeletal dynamics and cell motility to cell division, gene regulation, apical extrusion, angiogenesis, cellular metabolism and lipid metabolism. However, the expression of LIMA1 in malignant tumors and its mechanism of action have not yet been elucidated, and many problems and challenges remain to be addressed. Therefore, this review systematically describes the structure and biological functions of LIMA1 and explores its expression and regulatory mechanism in malignant tumors, and further discusses its clinical value and therapeutic prospects.
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Affiliation(s)
- Xiaoxiao Wang
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Chao Zhang
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Huangqin Song
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Junlong Yuan
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Xiaomin Zhang
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Yiran Yuan
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Lei Zhang
- Department of Hepatobiliary Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
- Hepatic Surgery Center, Institute of Hepato-Pancreato-Biliary Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jiefeng He
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
- Department of Hepatobiliary Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
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Mirzaei S, Gholami MH, Aghdaei HA, Hashemi M, Parivar K, Karamian A, Zarrabi A, Ashrafizadeh M, Lu J. Exosome-mediated miR-200a delivery into TGF-β-treated AGS cells abolished epithelial-mesenchymal transition with normalization of ZEB1, vimentin and Snail1 expression. ENVIRONMENTAL RESEARCH 2023; 231:116115. [PMID: 37178752 DOI: 10.1016/j.envres.2023.116115] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 05/05/2023] [Accepted: 05/11/2023] [Indexed: 05/15/2023]
Abstract
Exosomes are small extracellular vesicles that can be derived from human cells such as mesenchymal stem cells (MSCs). The size of exosomes is at nano-scale range and owing to their biocompatibility and other characteristics, they have been promising candidates for delivery of bioactive compounds and genetic materials in disease therapy, especially cancer therapy. Gastric cancer (GC) is a leading cause of death among patients and this malignant disease affects gastrointestinal tract that its invasiveness and abnormal migration mediate poor prognosis of patients. Metastasis is an increasing challenge in GC and microRNAs (miRNAs) are potential regulators of metastasis and related molecular pathways, especially epithelial-to-mesenchymal transition (EMT). In the present study, our aim was to explore role of exosomes in miRNA-200a delivery for suppressing EMT-mediated GC metastasis. Exosomes were isolated from MSCs via size exclusion chromatography. The synthetic miRNA-200a mimics were transfected into exosomes via electroporation. AGS cell line exposed to TGF-β for EMT induction and then, these cells cultured with miRNA-200a-loaded exosomes. The transwell assays performed to evaluate GC migration and expression levels of ZEB1, Snail1 and vimentin measured. Exosomes demonstrated loading efficiency of 5.92 ± 4.6%. The TGF-β treatment transformed AGS cells into fibroblast-like cells expressing two stemness markers, CD44 (45.28%) and CD133 (50.79%) and stimulated EMT. Exosomes induced a 14.89-fold increase in miRNA-200a expression in AGS cells. Mechanistically, miRNA-200a enhances E-cadherin levels (P < 0.01), while it decreases expression levels of β-catenin (P < 0.05), vimentin (P < 0.01), ZEB1 (P < 0.0001) and Snail1 (P < 0.01). Leading to EMT inhibition in GC cells. This pre-clinical experiment introduces a new strategy for miRNA-200a delivery that is of importance for preventing migration and invasion of GC cells.
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Affiliation(s)
- Sepideh Mirzaei
- Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | | | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorder Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Mehrdad Hashemi
- Department of Molecular and Cellular Sciences, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence Science Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Kazem Parivar
- Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran.
| | - Amin Karamian
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences. Tehran, Iran
| | - Ali Zarrabi
- Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, 34485, Istanbul, Turkey
| | - Milad Ashrafizadeh
- Department of General Surgery and Institute of Precision Diagnosis and Treatment of Digestive System Tumors, Carson International Cancer Center, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong, 518055, China; Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
| | - Jianlin Lu
- Department of Geriatrics, The Fifth People's Hospital of Wujiang District, Suzhou, China.
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Yang WJ, Zhao HP, Yu Y, Wang JH, Guo L, Liu JY, Pu J, Lv J. Updates on global epidemiology, risk and prognostic factors of gastric cancer. World J Gastroenterol 2023; 29:2452-2468. [PMID: 37179585 PMCID: PMC10167900 DOI: 10.3748/wjg.v29.i16.2452] [Citation(s) in RCA: 118] [Impact Index Per Article: 59.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 03/19/2023] [Accepted: 04/07/2023] [Indexed: 04/24/2023] Open
Abstract
Gastric cancer (GC) is defined as the primary epithelial malignancy derived from the stomach, and it is a complicated and heterogeneous disease with multiple risk factors. Despite its overall declining trend of incidence and mortality in various countries over the past few decades, GC remains the fifth most common malignancy and the fourth leading cause of cancer-related death globally. Although the global burden of GC has shown a significant downward trend, it remains severe in certain areas, such as Asia. GC ranks third in incidence and mortality among all cancer types in China, and it accounts for nearly 44.0% and 48.6% of new GC cases and GC-related deaths in the world, respectively. The regional differences in GC incidence and mortality are obvious, and annual new cases and deaths are increasing rapidly in some developing regions. Therefore, early preventive and screening strategies for GC are urgently needed. The clinical efficacies of conventional treatments for GC are limited, and the developing understanding of GC pathogenesis has increased the demand for new therapeutic regimens, including immune checkpoint inhibitors, cell immunotherapy and cancer vaccines. The present review describes the epidemiology of GC worldwide, especially in China, summarizes its risk and prognostic factors, and focuses on novel immunotherapies to develop therapeutic strategies for the management of GC patients.
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Affiliation(s)
- Wen-Juan Yang
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - He-Ping Zhao
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - Yan Yu
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - Ji-Han Wang
- Institute of Medical Research, Northwestern Polytechnical University, Xi'an 710072, Shaanxi Province, China
| | - Lei Guo
- Department of Spinal Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - Jun-Ye Liu
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - Jie Pu
- Department of Cardiology, Shaanxi Provincial People’s Hospital, Xi'an 710068, Shaanxi Province, China
| | - Jing Lv
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
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Huang H, Huang Z, Ge J, Yang J, Chen J, Xu B, Wu S, Zheng X, Chen L, Zhang X, Jiang J. CD226 identifies functional CD8+T cells in the tumor microenvironment and predicts a better outcome for human gastric cancer. Front Immunol 2023; 14:1150803. [PMID: 37056782 PMCID: PMC10086426 DOI: 10.3389/fimmu.2023.1150803] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 03/09/2023] [Indexed: 03/30/2023] Open
Abstract
It is well-known that CD226 serves as a critical activating receptor on various immune cells, such as lymphocytes and monocytes, and it is suggested to promote anti-tumor immunity in the tumor microenvironment (TME). Herein, we showed a crucial regulatory role of CD226 in CD8+T cell-mediated anti-tumor response in TME of human gastric cancer (GC). Specifically, the increased CD226 expression in cancer tissues was significantly associated with better clinical outcomes in GC patients. Moreover, the increased infiltrating CD226+CD8+T cells and the increased ratio of infiltrating CD226+CD8+T cells in CD8+T subpopulation within cancer tissues could also be valuable prognostic predictors for GC patients. Mechanically, the assay for transposase-accessible chromatin using sequencing (ATAC-seq) analysis revealed that the chromatin accessibility of CD226 in CD4+ and CD8+TILs was significantly higher than that in CD8+T cells in normal tissues. Further analysis showed that CD8+TILs highly expressed immune checkpoint molecules, such as TIGIT, LAG3, and HAVCR2, which means CD8+TILs are more exhausted. In addition, our multi-color immunohistochemical staining (mIHC) revealed that GC patients with higher frequency of IFN-γ+CD226+CD8+TILs showed poorer prognosis. Combined with the single-cell transcriptome sequencing (scRNA-seq) data analysis, we found that the expressions of IFN-γ and TIGIT in CD8+TILs were significantly and positively correlated. The expression of TIGIT in IFN-γ+CD226+CD8+TILs was higher, while that in IFN-γ-CD226+CD8+TILs was significantly lower. The correlation analysis showed that the expression of CD226 was positively correlated with the score of effector T cells but negatively correlated with that of immunosuppressive factors, such as Tregs and tumor-associated macrophages (TAMs). Collectively, we showed that the frequency of CD226+CD8+TILs was an excellent prognostic predictor for GC patients. Our findings provided insights into the interaction pattern between co-stimulatory receptor CD226 and tumor cells as well as the infiltrating immune cells in the TME in GC.
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Affiliation(s)
- Hao Huang
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
| | - Ziyi Huang
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, Jiangsu, China
- Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, Soochow University, Suzhou, Jiangsu, China
| | - Junwei Ge
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
| | - Jiayi Yang
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
| | - Junjun Chen
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
| | - Bin Xu
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
| | - Shaoxian Wu
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
| | - Xiao Zheng
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
| | - Lujun Chen
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- *Correspondence: Lujun Chen, ; Xueguang Zhang, ; Jingting Jiang,
| | - Xueguang Zhang
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, Jiangsu, China
- Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, Soochow University, Suzhou, Jiangsu, China
- *Correspondence: Lujun Chen, ; Xueguang Zhang, ; Jingting Jiang,
| | - Jingting Jiang
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- *Correspondence: Lujun Chen, ; Xueguang Zhang, ; Jingting Jiang,
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Wu YX, Zhou XY, Wang JQ, Chen GM, Chen JX, Wang RC, Huang JQ, Chen JS. Application of immune checkpoint inhibitors in immunotherapy for gastric cancer. Immunotherapy 2023; 15:101-115. [PMID: 36597704 DOI: 10.2217/imt-2022-0080] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Gastric cancer is the fifth most common cancer worldwide. With the development of immunotherapy, especially the application of immune checkpoint inhibitors (ICIs), the prognosis of advanced gastric cancer has improved. At present, ICIs combined with other therapies or dual ICI strategies in the treatment of advanced gastric cancer have shown clinical effectiveness and controllable safety. In addition, predictive biomarkers facilitate the precise selection of patients. Therefore, it is crucial to explore rational combinations and reliable predictive biomarkers for ICI therapy. This article reviews the recent advances in ICIs and relevant predictive biomarkers in the treatment of gastric cancer.
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Affiliation(s)
- Yi-Xiang Wu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Xiao-Yu Zhou
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Jian-Qi Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Gao-Min Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Jin-Xu Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Rong-Chang Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Jiong-Qiang Huang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Jing-Song Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
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Rizzo A, Mollica V, Tateo V, Tassinari E, Marchetti A, Rosellini M, De Luca R, Santoni M, Massari F. Hypertransaminasemia in cancer patients receiving immunotherapy and immune-based combinations: the MOUSEION-05 study. Cancer Immunol Immunother 2023; 72:1381-1394. [PMID: 36695827 DOI: 10.1007/s00262-023-03366-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 01/01/2023] [Indexed: 01/26/2023]
Abstract
BACKGROUND The antitumor efficacy of immune checkpoint inhibitors (ICIs) has increasingly emerged during the last few years. However, there is a need to identify the safety profile of these agents more comprehensively, including liver toxicity. MATERIALS AND METHODS Herein, we performed a meta-analysis to assess the risk of all-grade and grade 3-4 hypertransaminasemia in cancer patients receiving ICIs-as monotherapy or in combination with other anticancer agents. All the relevant trials were retrieved through EMBASE, Cochrane Library, and PubMed/Medline databases; eligible studies were selected according to PRISMA statement. The pooled relative risk (RR) and 95% confidence interval (CI) were extracted. RESULTS Fifty-nine studies were included. The pooled RRs for all-grade AST and ALT increase were 1.45 (95% CI 1.26-1.67) (Supplementary Fig. 3) and 1.51 (95% CI 1.29-1.77) in patients receiving ICIs monotherapy and immune-based combinations compared to control treatment, respectively. The pooled RRs for grade 3-4 AST and ALT increase were 2.16 (95% CI 1.77-2.64) and 2.3 (95% CI 1.91-2.77). CONCLUSIONS According to our results, ICIs monotherapy and immune-based combinations were associated with higher risk of all-grade and grade 3-4 hypertransaminasemia. Monitoring liver function should be recommended in cancer patients treated with ICIs monotherapy or immune-based combination, and in case of underlying liver disease, a careful risk-benefit assessment appears as a mandatory need.
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Affiliation(s)
- Alessandro Rizzo
- Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico "Don Tonino Bello", Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Istituto Tumori Giovanni Paolo II-Bari, Viale Orazio Flacco 65, 70124, Bari, Italy
| | - Veronica Mollica
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni-15, 40138, Bologna, Italy.
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138, Bologna, Italy.
| | - Valentina Tateo
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni-15, 40138, Bologna, Italy
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138, Bologna, Italy
| | - Elisa Tassinari
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni-15, 40138, Bologna, Italy
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138, Bologna, Italy
| | - Andrea Marchetti
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni-15, 40138, Bologna, Italy
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138, Bologna, Italy
| | - Matteo Rosellini
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni-15, 40138, Bologna, Italy
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138, Bologna, Italy
| | - Raffaele De Luca
- Department of Surgical Oncology, IRCCS Istituto Tumori 'Giovanni Paolo II', Viale Orazio Flacco, 65, 70124, Bari, Italy
| | | | - Francesco Massari
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni-15, 40138, Bologna, Italy
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138, Bologna, Italy
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Ni L, Chen S, Liu J, Li H, Zhao H, Zheng C, Zhang Y, Huang H, Huang J, Wang B, Lin C. GPR176 Is a Biomarker for Predicting Prognosis and Immune Infiltration in Stomach Adenocarcinoma. Mediators Inflamm 2023; 2023:7123568. [PMID: 37124060 PMCID: PMC10132901 DOI: 10.1155/2023/7123568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 10/28/2022] [Accepted: 03/27/2023] [Indexed: 05/02/2023] Open
Abstract
Immunotherapy based on immune checkpoint inhibitors (ICIs) is considered to be a promising treatment for stomach adenocarcinoma (STAD), but only a minority of patients benefit from it. It is believed that the poor therapeutic efficacy is attributed to the complex tumor immune microenvironment (TIM) of STAD. Therefore, elucidating the specific regulatory mechanism of TIM in STAD is critical. Previous study suggests that GRP176 may be involved in regulating the pace of circadian behavior, and its role in tumors has not been reported. In this study, we first found that GPR176 was highly expressed in STAD and negatively correlated with patient prognosis. Next, we investigated the relationship between GPR176 and clinical characteristics, and the results showed that the stage is closely related to the level of GPR176. In addition, our further analysis found that GRP176 expression level was significantly correlated with chemotherapeutic drug sensitivity and ICI response. KEGG and GO analyses showed that GPR176 might be involved in stromal remodeling of STAD. Furthermore, we analyzed the association between GPR176 expression and immune implication, and the results revealed that GPR176 was negatively related to the infiltration of various immune cells. Interestingly, GPR176 induced the conversion of TIM while reducing the tumor immune burden (TMB). The expression of GRP176 is closely related to the level of various immunomodulators. Moreover, we performed univariate and multivariate regression analyses on the immunomodulators and finally obtained 4 genes (CRCR4, TNSF18, PDCD1, and TGFB1). Then, we constructed a GRP176-related immunomodulator prognostic model (GRIM) based on the above 4 genes, which was validated to have good predictive power. Finally, we developed a nomogram based on the risk score of GRIM and verified its accuracy. These results suggested that GPR176 is closely related to the prognosis and TIM of STAD. GPR176 may be a new potential target for immunotherapy in STAD.
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Affiliation(s)
- Lin Ni
- Department of General Surgery, 900TH Hospital of Joint Logistics Support Force (Fuzong Clinical Medical College) (Former Fuzhou General Hospital), Fuzhou, Fujian, China
| | - Shuming Chen
- Department of General Surgery, 900TH Hospital of Joint Logistics Support Force (Fuzong Clinical Medical College) (Former Fuzhou General Hospital), Fuzhou, Fujian, China
| | - Jianyong Liu
- Department of Hepatobiliary Surgery, 900TH Hospital of Joint Logistics Support Force (Fuzong Clinical Medical College) (Former Fuzhou General Hospital), Fuzhou, Fujian, China
| | - He Li
- Department of General Surgery, 900TH Hospital of Joint Logistics Support Force (Fuzong Clinical Medical College) (Former Fuzhou General Hospital), Fuzhou, Fujian, China
| | - Hu Zhao
- Department of General Surgery, 900TH Hospital of Joint Logistics Support Force (Fuzong Clinical Medical College) (Former Fuzhou General Hospital), Fuzhou, Fujian, China
| | - Chunhua Zheng
- Department of General Surgery, 900TH Hospital of Joint Logistics Support Force (Fuzong Clinical Medical College) (Former Fuzhou General Hospital), Fuzhou, Fujian, China
| | - Yawei Zhang
- Department of General Surgery, 900TH Hospital of Joint Logistics Support Force (Fuzong Clinical Medical College) (Former Fuzhou General Hospital), Fuzhou, Fujian, China
| | - Hancong Huang
- Department of General Surgery, 900TH Hospital of Joint Logistics Support Force (Fuzong Clinical Medical College) (Former Fuzhou General Hospital), Fuzhou, Fujian, China
| | - Junjie Huang
- Department of General Surgery, 900TH Hospital of Joint Logistics Support Force (Fuzong Clinical Medical College) (Former Fuzhou General Hospital), Fuzhou, Fujian, China
| | - Bing Wang
- Department of General Surgery, 900TH Hospital of Joint Logistics Support Force (Fuzong Clinical Medical College) (Former Fuzhou General Hospital), Fuzhou, Fujian, China
| | - Chengzhi Lin
- Department of General Surgery, 900TH Hospital of Joint Logistics Support Force (Fuzong Clinical Medical College) (Former Fuzhou General Hospital), Fuzhou, Fujian, China
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36
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Zhang Q, Wang C, Yang Y, Xu R, Li Z. LncRNA and its role in gastric cancer immunotherapy. Front Cell Dev Biol 2023; 11:1052942. [PMID: 36875764 PMCID: PMC9978521 DOI: 10.3389/fcell.2023.1052942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Accepted: 01/30/2023] [Indexed: 02/18/2023] Open
Abstract
Gastric cancer (GC) is a potential dominant disease in tumor immunotherapy checkpoint inhibitors, and adoptive cell therapy have brought great hope to GC patients. However, only some patients with GC can benefit from immunotherapy, and some patients develop drug resistance. More and more studies have shown that long non-coding RNAs (lncRNAs) may be important in GC immunotherapy's prognosis and drug resistance. Here, we summarize the differential expression of lncRNAs in GC and their impact on the curative effect of GC immunotherapy, discuss potential mechanisms of activity in GC immunotherapy resistance regulated by lncRNAs. This paper reviews the differential expression of lncRNA in GC and its effect on immunotherapy efficacy in GC. In terms of genomic stability, inhibitory immune checkpoint molecular expression, the cross-talk between lncRNA and immune-related characteristics of GC was summarized, including tumor mutation burden (TMB), microsatellite instability (MSI), and Programmed death 1 (PD-1). At the same time, this paper reviewed the mechanism of tumor-induced antigen presentation and upregulation of immunosuppressive factors, as well as the association between Fas system and lncRNA, immune microenvironment (TIME) and lncRNA, and summarized the functional role of lncRNA in tumor immune evasion and immunotherapy resistance.
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Affiliation(s)
- Qiang Zhang
- Department of Digestive endoscopy, Jiangsu Province Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Chuanchi Wang
- Xin-Huangpu Joint Innovation Institute of Chinese Medicine, Guangzhou, Guangdong, China.,China Science and Technology Development Center of Chinese Medicine, Beijing, China
| | - Yan Yang
- China Science and Technology Development Center of Chinese Medicine, Beijing, China
| | - Ruihan Xu
- The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Ziyun Li
- Acupuncture and Tuina college, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
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Li H, Lin D, Yu Z, Li H, Zhao S, Hainisayimu T, Liu L, Wang K. A nomogram model based on the number of examined lymph nodes-related signature to predict prognosis and guide clinical therapy in gastric cancer. Front Immunol 2022; 13:947802. [PMID: 36405735 PMCID: PMC9667298 DOI: 10.3389/fimmu.2022.947802] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 09/30/2022] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Increasing evidence suggests that the number of examined lymph nodes (ELNs) is strongly linked to the survivorship of gastric cancer (GC). The goal of this study was to assess the prognostic implications of the ELNs number and to construct an ELNs-based risk signature and nomogram model to predict overall survival (OS) characteristics in GC patients. METHODS This inception cohort study included 19,317 GC patients from the U.S. Surveillance, Epidemiology, and End Results (SEER) database, who were separated into a training group and an internal validation group. The nomogram was built with the training set, then internally verified with SEER data, and externally validated with two different data sets. Based on the RNA-seq data, ELNs-related DERNAs (DElncRNAs, DEmiRNAs, andDEmRNAs) and immune cells were identified. The LASSO-Cox regression analysis was utilized to construct ELNs-related DERNAs and immune cell prognostic signature in The Cancer Genome Atlas (TCGA) cohort. The OS of subgroups with high- and low-ELN signature was compared using the Kaplan-Meier (K-M) analysis. A nomogram was successfully constructed based on the ELNs signature and other clinical characteristics. The concordance index (C-index), calibration plot, receiver operating characteristic curve, and decision curve analysis (DCA) were all used to evaluate the nomogram model. The meta-analysis, the Gene Expression Profiling Interactive Analysis database, and reverse transcription-quantitative PCR (RT-qPCR) were utilized to validate the RNA expression or abundance of prognostic genes and immune cells between GC tissues and normal gastric tissues, respectively. Finally, we analyzed the correlations between immune checkpoints, chemotherapy drug sensitivity, and risk score. RESULTS The multivariate analysis revealed that the high ELNs improved OS compared with low ELNs (hazard ratio [HR] = 0.659, 95% confidence interval [CI]: 0.626-0.694, p < 0.0001). Using the training set, a nomogram incorporating ELNs was built and proven to have good calibration and discrimination (C-index [95% CI], 0.714 [0.710-0.718]), which was validated in the internal validation set (C-index [95% CI], 0.720 [0.714-0.726]), the TCGA set (C-index [95% CI], 0.693 [0.662-0.724]), and the Chinese set (C-index [95% CI], 0.750 [0.720-0.782]). An ELNs-related signature model based on ELNs group, regulatory T cells (Tregs), neutrophils, CDKN2B-AS1, H19, HOTTIP, LINC00643, MIR663AHG, TMEM236, ZNF705A, and hsa-miR-135a-5p was constructed by the LASSO-Cox regression analysis. The result showed that OS was remarkably lower in patients with high-ELNs signature compared with those with low-ELN signature (HR = 2.418, 95% CI: 1.804-3.241, p < 0.001). This signature performed well in predicting 1-, 3-, and 5-year survival (AUC [95% CI] = 0.688 [0.612-0.763], 0.744 [0.659-0.830], and 0.778 [0.647-0.909], respectively). The multivariate Cox analysis illustrated that the risk score was an independent predictor of survival for patients with GC. Moreover, the expression of prognostic genes (LINC00643, TMEM236, and hsa-miR-135a-5p) displayed differences between GC tissues and adjacent non-tumor tissues. The C-index of the nomogram that can be used to predict the OS of GC patients was 0.710 (95% CI: 0.663-0.753). Both the calibration plots and DCA showed that the nomogram has good predictive performance. Moreover, the signature was significantly correlated with the N stage and T stage. According to our analysis, GC patients in the low-ELN signature group may have a better immunotherapy response and OS outcome. CONCLUSIONS We explored the prognostic role of ELNs in GC and successfully constructed an ELNs signature linked to the GC prognosis in TCGA. The findings manifested that the signature is a powerful predictive indicator for patients with GC. The signature might contain potential biomarkers for treatment response prediction for GC patients. Additionally, we identified a novel and robust nomogram combining the characteristics of ELNs and clinical factors for predicting 1-, 3-, and 5-year OS in GC patients, which will facilitate personalized survival prediction and aid clinical decision-making in GC patients.
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Affiliation(s)
- Huling Li
- School of Public Health, Xinjiang Medical University, Urumqi, China
| | - Dandan Lin
- School of Public Health, Xinjiang Medical University, Urumqi, China
| | - Zhen Yu
- Department of Gastrointestinal Surgery, The Third Affiliated Hospital, Xinjiang Medical University, Urumqi, China
| | - Hui Li
- Central Laboratory of Xinjiang Medical University, Urumqi, China
| | - Shi Zhao
- JC School of Public Health and Primary Care, Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Tuersun Hainisayimu
- Department of Biochemistry and Molecular Biology, Basic Medicine School, Xinjiang Medical University, Urumqi, China
| | - Lin Liu
- Department of Gastrointestinal Surgery, The Third Affiliated Hospital, Xinjiang Medical University, Urumqi, China,*Correspondence: Kai Wang, ; Lin Liu,
| | - Kai Wang
- Department of Medical Engineering and Technology, Xinjiang Medical University, Urumqi, China,*Correspondence: Kai Wang, ; Lin Liu,
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Zhou Y, Yu K. Th1, Th2, and Th17 cells and their corresponding cytokines are associated with anxiety, depression, and cognitive impairment in elderly gastric cancer patients. Front Surg 2022; 9:996680. [PMID: 36386524 PMCID: PMC9640774 DOI: 10.3389/fsurg.2022.996680] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 09/09/2022] [Indexed: 11/06/2022] Open
Abstract
Objective T helper (Th) cells modulate the stress response, oxidative stress, and neuroinflammation to mediate anxiety, depression, and cognitive impairment. This study intended to explore the association between Th cells and anxiety, depression, and cognitive impairment in elderly gastric cancer patients. Methods Totally, 176 elderly gastric cancer patients were enrolled in this study. Peripheral blood samples were collected. Th1, Th2, and Th17 cells were detected by flow cytometry; their corresponding cytokines were examined by ELISA. The Hospital Anxiety and Depression Scale (HADS) and Mini-Mental State Examination (MMSE) were assessed. Results In total, 42.0%, 33.0%, and 19.9% of elderly gastric cancer patients presented anxiety, depression, and cognitive impairment, respectively. Th1 (P = 0.016), Th17 (P = 0.009), and IL-17A (P = 0.001) were positively associated with the HADS-A score. Th17 (P = 0.003) and IL-17A (P = 0.009) levels were increased in patients with anxiety compared with those without anxiety. Concurrently, a positive association was observed for Th1 (P = 0.027), Th17 (P = 0.014), and IFN-γ (P = 0.049) with the HADS-D score. Th1 (P = 0.017) and Th17 (P = 0.049) levels were increased in patients with depression than in those without depression. Moreover, Th1 (P = 0.003), Th17 (P < 0.001), IFN-γ (P = 0.014), and IL-17A (P < 0.001) were inversely related to MMSE scores, but only Th17 (P < 0.001) and IL-17A (P < 0.001) were increased in patients with cognitive impairment compared with those without cognitive impairment. Conclusion Th1 and Th17 cells reflect anxiety, depression, and cognitive impairment risk to a certain extent in elderly gastric cancer patients, implying their involvement in the pathology of the abovementioned psychological and cognitive issues. However, further validation is needed.
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Affiliation(s)
- Yanxia Zhou
- Nursing Department, Chenzhou First People’s Hospital of Hunan Province, Chenzhou, China
| | - Ke Yu
- Operation Room, Changsha Hospital for Maternal / Child Health Care Affiliated to Hunan Normal University, Changsha, China
- Correspondence: Ke Yu
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Comprehensive Analysis of the Immune Implication of AKAP12 in Stomach Adenocarcinoma. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:3445230. [PMID: 36148016 PMCID: PMC9489422 DOI: 10.1155/2022/3445230] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 08/16/2022] [Accepted: 08/20/2022] [Indexed: 11/17/2022]
Abstract
A kinase anchor protein 12 (AKAP12) as a tumor suppressor in various cancers has been extensively studied and confirmed. However, its immune implication in stomach adenocarcinoma (STAD) remains uncertain. Here, using The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), Tumor Immune Estimation Resource (TIMER), Cancer Cell Line Encyclopedia (CCLE), integrated repository portal for tumor-immune system interactions (TISIDB), and Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) database, we systematically analyzed the immune correlation of AKAP12 from three aspects including immune infiltration cells, immune-related pathways, and immunomodulators and developed a AKAP12-related 4-gene signature for prognosis prediction. Our results showed that AKAP12 mRNA and protein levels were downregulated in STAD patients, and its expression was positively related to CD4+ T cells and macrophages. In addition, the immune cell infiltration levels were associated with AKAP12 gene copy number deletion in STAD. Based on CCLE database, we found that AKAP12 coexpressed genes were enriched in several immune- and cancer-related pathways, which was further validated by Gene Set Enrichment Analysis (GSEA). Moreover, we identified 46 immunomodulators that were significantly related to AKAP12 expression using TISIDB database, and these immunomodulators were involved in immune-related pathways including Th17 cell differentiation and natural killer cell-mediated cytotoxicity. Additionally, based on the 46 AKAP12-related immunomodulators, a 4-gene risk prediction signature was developed using the Cox regression model. The risk signature was identified as an independent prognostic factor, which can accurately predict the prognosis of patients with STAD, showing good predictive performance. Furthermore, we constructed a prognostic nomogram and calibration to predict and assess patient survival probabilities by integrating the risk score and other clinical factors. In conclusion, our study provides strong evidence that AKAP12 is closely related to tumor immunity in STAD from three aspects: immune infiltration cells, immune pathways, and immunomodulators. More importantly, the AKAP12-related prognostic signature may have a good application prospect for clinical practice.
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Xin D, Man Y, Yang Y, Wang F. A novel prognostic and therapeutic target biomarker based on necroptosis-related gene signature and immune microenvironment infiltration in gastric cancer. Front Genet 2022; 13:953997. [PMID: 36092932 PMCID: PMC9452725 DOI: 10.3389/fgene.2022.953997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 07/27/2022] [Indexed: 11/13/2022] Open
Abstract
Background: Gastric cancer is a major global public health burden worldwide. Although treatment strategies are continuously improving, the overall prognosis remains poor. Necroptosis is a newly discovered form of cell death associated with anti-tumor immunity.Methods: Gastric cancer (GC) data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were downloaded. Bioinformatics analysis was performed to construct a necroptosis-related risk model and to establish cancer subtypes. Potential associations of the tumor immune microenvironment and immunotherapy response with necroptosis-related prognostic risk score (NRG risk score) were comprehensively explored. 16 GC and paired normal tissues were collected and RT-PCR was performed to examine expression of NRG related genes.Results: GC samples were stratified into three subtypes according to prognostic necroptosis gene expression. A necroptosis risk model based on 12 genes (NPC1L1, GAL, RNASE1, PCDH7, NOX4, GJA4, SLC39A4, BASP1, BLVRA, NCF1, PNOC, and CCR5) was constructed and validated. The model was significantly associated with the OS and PFS of GC patients and the tumor immune microenvironment including immune cell infiltration, microsatellite instability (MSI) status, tumor mutational burden (TMB) score, immune checkpoint, and human leukocyte antigen (HLA) gene expression. A prognostic nomogram based on the NRG_score was additionally constructed. A low NRG risk score was correlated with high tumor immunogenicity and might benefit from immunotherapy.Conclusion: We have identified a useful prognostic model based on necroptosis-related genes in GC and comprehensively the relationship between necroptosis and tumor immunity. Predicting value to immunotherapy response is promising, and further research to validate the model in clinical practice is needed.
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Affiliation(s)
- Dao Xin
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yuxin Man
- Department of Medical Oncology, Sichuan Cancer Hospital, Medical School of University of Electronic Science and Technology of China, Chengdu, China
| | - Yalan Yang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Feng Wang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- *Correspondence: Feng Wang,
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Che H, Xiong Q, Ma J, Chen S, Wu H, Xu H, Hou B. Association of Helicobacter pylori infection with survival outcomes in advanced gastric cancer patients treated with immune checkpoint inhibitors. BMC Cancer 2022; 22:904. [PMID: 35986342 PMCID: PMC9389789 DOI: 10.1186/s12885-022-10004-9] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 08/12/2022] [Indexed: 12/24/2022] Open
Abstract
Abstract
Background
Accumulating evidence has revealed that the gut microbiota influences the effectiveness of immune checkpoint inhibitors (ICIs) in cancer patients. As a part of the human microbiome, Helicobacter pylori (H. pylori) was reported to be associated with reduced effectiveness of anti-PD1 immunotherapy in patients with non-small-cell lung cancer (NSCLC). Gastric cancer is more closely related to H. pylori, so we conducted a retrospective analysis to verify whether the association of H. pylori and effectiveness is applicable to advanced gastric cancer (AGC) patients.
Material and methods
AGC patients who had evidence of H. pylori and received anti-PD-1 antibodies were enrolled in the study. The differences in the disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) between the H. pylori-positive group and the negative group were compared.
Results
A total of 77 patients were included in this study; 34 patients were H. pylori positive, and the prevalence of H. pylori infection was 44.2%. Compared with the H. pylori-negative group, patients in the H. pylori-positive group had a higher risk of nonclinical response to anti-PD-1 antibody, with an OR of 2.91 (95% CI: 1.13–7.50). Patients in the H. pylori-negative group had a longer OS and PFS than those in the positive group, with an estimated median OS of 17.5 months vs. 6.2 months (HR = 2.85, 95% CI: 1.70–4.78; P = 0.021) and a median PFS of 8.4 months vs. 2.7 months (HR = 3.11, 95% CI: 1.96–5.07, P = 0.008). Multivariate analysis indicated that H. pylori infection was independently associated with PFS (HR = 1.90, 95% CI: 1.10–3.30; P = 0.022).
Conclusion
Our study unveils for the first time that H. pylori infection is associated with the outcome of immunotherapy for AGC patients. Multicenter, large sample and prospective clinical studies are needed to verify the association.
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Li B, Liang L, Chen Y, Liu J, Wang Z, Mao Y, Zhao K, Chen J. Circ_0008287 promotes immune escape of gastric cancer cells through impairing microRNA-548c-3p-dependent inhibition of CLIC1. Int Immunopharmacol 2022; 111:108918. [PMID: 35905561 DOI: 10.1016/j.intimp.2022.108918] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 05/23/2022] [Accepted: 05/30/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Analyses in silico suggested the upregulation of a circular RNA (circRNA), circ_0008287, in gastric cancer and possible interactions among microRNA (miR)-548c-3p, circ_0008287, and intracellular chloride channel protein 1 (CLIC1). This study aims to testify whether circ_0008287 can affect the immune escape of gastric cancer cells by regulating miR-548c-3p and CLIC1. METHODS RT-qPCR was performed to determine the expression pattern of circ_0008287 in gastric cancer cells. Gain- and loss-of function assays were then performed to assess the effects of circ_0008287 on malignant phenotypes of cancer cells. Interactions among circ_0008287, miR-548c-3p and CLIC1 were verified by dual luciferase reporter gene, RIP and FISH assays. Effects of CLIC1 on IFN-γ secretion and apoptosis in CD8 + T cells were evaluated by flow cytometry following co-culture of CD8 + T cells with cancer cells overexpressing/silencing CLIC1. A gastric cancer mouse model was further developed for in vivo investigation on effects of circ_0008287 on tumorigenesis and tumor metastasis. RESULTS circ_0008287, an upregulated circRNA in gastric cancer cells, augmented the viability as well as invasive and migratory potentials of gastric cancer cells. By competitively binding to miR-548c-3, circ_0008287 increased the expression of CLIC1, which impaired the function of CD8 + T cells and promoted their apoptosis. After downregulation of circ_0008287, in vivo tumorigenesis and metastasis were suppressed. CONCLUSION Hence, this study suggests the promotive role of circ_0008287 in gastric cancer progression and immune escape and further elucidates the underlying circ_0008287/miR-548c-3p/CLIC1 regulatory axis.
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Affiliation(s)
- Bopei Li
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, P.R. China; Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, P.R. China
| | - Liang Liang
- Department of General Surgery, the Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, P.R. China
| | - Yeyang Chen
- Departments of Gastrointestinal Surgery, The First People's Hospital of Yulin, Yulin 537000, P.R. China
| | - Jinlu Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, P.R. China
| | - Zhen Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, P.R. China
| | - Yuantian Mao
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, P.R. China
| | - Kun Zhao
- Departments of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, P.R. China
| | - Junqiang Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, P.R. China; Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, P.R. China.
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Jin X, Liu Z, Yang D, Yin K, Chang X. Recent Progress and Future Perspectives of Immunotherapy in Advanced Gastric Cancer. Front Immunol 2022; 13:948647. [PMID: 35844558 DOI: 10.3389/fimmu.2022.948647%' and 2*3*8=6*8 and 'r4tf'!='r4tf%] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 06/06/2022] [Indexed: 01/29/2024] Open
Abstract
As one of the most common forms of solid tumours, gastric carcinoma has been revealed as the third leading cause of death worldwide. The symptom of gastric cancer is usually not obvious and thus difficult to detect at earlier stages. Therefore, gastric cancer is already in the advanced stage once detected in patients, which has a poor prognosis due to ineffective therapies and multiple resistance. Recent advance in understanding the microenvironment of cancer has significantly promoted the development of immunotherapy for advanced gastric cancer. Immunotherapy can induce immune responses in gastric cancer patients thus leads to the destruction of cancer cells. In comparison of traditional therapy, immunotherapy has demonstrated robust efficacy and tolerable toxicity. Therefore, this novel strategy for treatment of advanced gastric cancer has gain increasingly popularity. In this review, we summarize recent progress of immunotherapy in advanced gastric cancer, such as immune check point inhibitors, adoptive cell therapy, VEGF inhibitors, cancer vaccines and CAR-T cell therapy. We highlight immunotherapies involved in clinical applications and discuss the existing challenges of current immunotherapies and promising strategies to overcome these limitations.
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Affiliation(s)
- Xin Jin
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, China
| | - Zhaorui Liu
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Dongxiao Yang
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Kai Yin
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Xusheng Chang
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
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Jin X, Liu Z, Yang D, Yin K, Chang X. Recent Progress and Future Perspectives of Immunotherapy in Advanced Gastric Cancer. Front Immunol 2022; 13:948647. [PMID: 35844558 DOI: 10.3389/fimmu.2022.948647'"] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 06/06/2022] [Indexed: 01/29/2024] Open
Abstract
As one of the most common forms of solid tumours, gastric carcinoma has been revealed as the third leading cause of death worldwide. The symptom of gastric cancer is usually not obvious and thus difficult to detect at earlier stages. Therefore, gastric cancer is already in the advanced stage once detected in patients, which has a poor prognosis due to ineffective therapies and multiple resistance. Recent advance in understanding the microenvironment of cancer has significantly promoted the development of immunotherapy for advanced gastric cancer. Immunotherapy can induce immune responses in gastric cancer patients thus leads to the destruction of cancer cells. In comparison of traditional therapy, immunotherapy has demonstrated robust efficacy and tolerable toxicity. Therefore, this novel strategy for treatment of advanced gastric cancer has gain increasingly popularity. In this review, we summarize recent progress of immunotherapy in advanced gastric cancer, such as immune check point inhibitors, adoptive cell therapy, VEGF inhibitors, cancer vaccines and CAR-T cell therapy. We highlight immunotherapies involved in clinical applications and discuss the existing challenges of current immunotherapies and promising strategies to overcome these limitations.
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Affiliation(s)
- Xin Jin
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, China
| | - Zhaorui Liu
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Dongxiao Yang
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Kai Yin
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Xusheng Chang
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
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Jin X, Liu Z, Yang D, Yin K, Chang X. Recent Progress and Future Perspectives of Immunotherapy in Advanced Gastric Cancer. Front Immunol 2022; 13:948647. [PMID: 35844558 DOI: 10.3389/fimmu.2022.948647" and 2*3*8=6*8 and "hxww"="hxww] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 06/06/2022] [Indexed: 01/29/2024] Open
Abstract
As one of the most common forms of solid tumours, gastric carcinoma has been revealed as the third leading cause of death worldwide. The symptom of gastric cancer is usually not obvious and thus difficult to detect at earlier stages. Therefore, gastric cancer is already in the advanced stage once detected in patients, which has a poor prognosis due to ineffective therapies and multiple resistance. Recent advance in understanding the microenvironment of cancer has significantly promoted the development of immunotherapy for advanced gastric cancer. Immunotherapy can induce immune responses in gastric cancer patients thus leads to the destruction of cancer cells. In comparison of traditional therapy, immunotherapy has demonstrated robust efficacy and tolerable toxicity. Therefore, this novel strategy for treatment of advanced gastric cancer has gain increasingly popularity. In this review, we summarize recent progress of immunotherapy in advanced gastric cancer, such as immune check point inhibitors, adoptive cell therapy, VEGF inhibitors, cancer vaccines and CAR-T cell therapy. We highlight immunotherapies involved in clinical applications and discuss the existing challenges of current immunotherapies and promising strategies to overcome these limitations.
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Affiliation(s)
- Xin Jin
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, China
| | - Zhaorui Liu
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Dongxiao Yang
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Kai Yin
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Xusheng Chang
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
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Jin X, Liu Z, Yang D, Yin K, Chang X. Recent Progress and Future Perspectives of Immunotherapy in Advanced Gastric Cancer. Front Immunol 2022; 13:948647. [PMID: 35844558 DOI: 10.3389/fimmu.2022.948647'||'] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 06/06/2022] [Indexed: 01/29/2024] Open
Abstract
As one of the most common forms of solid tumours, gastric carcinoma has been revealed as the third leading cause of death worldwide. The symptom of gastric cancer is usually not obvious and thus difficult to detect at earlier stages. Therefore, gastric cancer is already in the advanced stage once detected in patients, which has a poor prognosis due to ineffective therapies and multiple resistance. Recent advance in understanding the microenvironment of cancer has significantly promoted the development of immunotherapy for advanced gastric cancer. Immunotherapy can induce immune responses in gastric cancer patients thus leads to the destruction of cancer cells. In comparison of traditional therapy, immunotherapy has demonstrated robust efficacy and tolerable toxicity. Therefore, this novel strategy for treatment of advanced gastric cancer has gain increasingly popularity. In this review, we summarize recent progress of immunotherapy in advanced gastric cancer, such as immune check point inhibitors, adoptive cell therapy, VEGF inhibitors, cancer vaccines and CAR-T cell therapy. We highlight immunotherapies involved in clinical applications and discuss the existing challenges of current immunotherapies and promising strategies to overcome these limitations.
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Affiliation(s)
- Xin Jin
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, China
| | - Zhaorui Liu
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Dongxiao Yang
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Kai Yin
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Xusheng Chang
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
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Jin X, Liu Z, Yang D, Yin K, Chang X. Recent Progress and Future Perspectives of Immunotherapy in Advanced Gastric Cancer. Front Immunol 2022; 13:948647. [PMID: 35844558 PMCID: PMC9284215 DOI: 10.3389/fimmu.2022.948647] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 06/06/2022] [Indexed: 12/15/2022] Open
Abstract
As one of the most common forms of solid tumours, gastric carcinoma has been revealed as the third leading cause of death worldwide. The symptom of gastric cancer is usually not obvious and thus difficult to detect at earlier stages. Therefore, gastric cancer is already in the advanced stage once detected in patients, which has a poor prognosis due to ineffective therapies and multiple resistance. Recent advance in understanding the microenvironment of cancer has significantly promoted the development of immunotherapy for advanced gastric cancer. Immunotherapy can induce immune responses in gastric cancer patients thus leads to the destruction of cancer cells. In comparison of traditional therapy, immunotherapy has demonstrated robust efficacy and tolerable toxicity. Therefore, this novel strategy for treatment of advanced gastric cancer has gain increasingly popularity. In this review, we summarize recent progress of immunotherapy in advanced gastric cancer, such as immune check point inhibitors, adoptive cell therapy, VEGF inhibitors, cancer vaccines and CAR-T cell therapy. We highlight immunotherapies involved in clinical applications and discuss the existing challenges of current immunotherapies and promising strategies to overcome these limitations.
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Affiliation(s)
- Xin Jin
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, China
| | - Zhaorui Liu
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Dongxiao Yang
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
- *Correspondence: Dongxiao Yang, ; Kai Yin, ; Xusheng Chang,
| | - Kai Yin
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
- *Correspondence: Dongxiao Yang, ; Kai Yin, ; Xusheng Chang,
| | - Xusheng Chang
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
- *Correspondence: Dongxiao Yang, ; Kai Yin, ; Xusheng Chang,
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48
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Jin X, Liu Z, Yang D, Yin K, Chang X. Recent Progress and Future Perspectives of Immunotherapy in Advanced Gastric Cancer. Front Immunol 2022; 13:948647. [PMID: 35844558 DOI: 10.3389/fimmu.2022.948647bsd3bmst] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 06/06/2022] [Indexed: 01/29/2024] Open
Abstract
As one of the most common forms of solid tumours, gastric carcinoma has been revealed as the third leading cause of death worldwide. The symptom of gastric cancer is usually not obvious and thus difficult to detect at earlier stages. Therefore, gastric cancer is already in the advanced stage once detected in patients, which has a poor prognosis due to ineffective therapies and multiple resistance. Recent advance in understanding the microenvironment of cancer has significantly promoted the development of immunotherapy for advanced gastric cancer. Immunotherapy can induce immune responses in gastric cancer patients thus leads to the destruction of cancer cells. In comparison of traditional therapy, immunotherapy has demonstrated robust efficacy and tolerable toxicity. Therefore, this novel strategy for treatment of advanced gastric cancer has gain increasingly popularity. In this review, we summarize recent progress of immunotherapy in advanced gastric cancer, such as immune check point inhibitors, adoptive cell therapy, VEGF inhibitors, cancer vaccines and CAR-T cell therapy. We highlight immunotherapies involved in clinical applications and discuss the existing challenges of current immunotherapies and promising strategies to overcome these limitations.
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Affiliation(s)
- Xin Jin
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, China
| | - Zhaorui Liu
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Dongxiao Yang
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Kai Yin
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Xusheng Chang
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
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49
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Jin X, Liu Z, Yang D, Yin K, Chang X. Recent Progress and Future Perspectives of Immunotherapy in Advanced Gastric Cancer. Front Immunol 2022; 13:948647. [PMID: 35844558 DOI: 10.3389/fimmu.2022.948647' and 2*3*8=6*8 and 'fifm'='fifm] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 06/06/2022] [Indexed: 01/29/2024] Open
Abstract
As one of the most common forms of solid tumours, gastric carcinoma has been revealed as the third leading cause of death worldwide. The symptom of gastric cancer is usually not obvious and thus difficult to detect at earlier stages. Therefore, gastric cancer is already in the advanced stage once detected in patients, which has a poor prognosis due to ineffective therapies and multiple resistance. Recent advance in understanding the microenvironment of cancer has significantly promoted the development of immunotherapy for advanced gastric cancer. Immunotherapy can induce immune responses in gastric cancer patients thus leads to the destruction of cancer cells. In comparison of traditional therapy, immunotherapy has demonstrated robust efficacy and tolerable toxicity. Therefore, this novel strategy for treatment of advanced gastric cancer has gain increasingly popularity. In this review, we summarize recent progress of immunotherapy in advanced gastric cancer, such as immune check point inhibitors, adoptive cell therapy, VEGF inhibitors, cancer vaccines and CAR-T cell therapy. We highlight immunotherapies involved in clinical applications and discuss the existing challenges of current immunotherapies and promising strategies to overcome these limitations.
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Affiliation(s)
- Xin Jin
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, China
| | - Zhaorui Liu
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Dongxiao Yang
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Kai Yin
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Xusheng Chang
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
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50
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Jin X, Liu Z, Yang D, Yin K, Chang X. Recent Progress and Future Perspectives of Immunotherapy in Advanced Gastric Cancer. Front Immunol 2022; 13:948647. [PMID: 35844558 DOI: 10.3389/fimmu.2022.948647����%2527%2522\'\"] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 06/06/2022] [Indexed: 01/29/2024] Open
Abstract
As one of the most common forms of solid tumours, gastric carcinoma has been revealed as the third leading cause of death worldwide. The symptom of gastric cancer is usually not obvious and thus difficult to detect at earlier stages. Therefore, gastric cancer is already in the advanced stage once detected in patients, which has a poor prognosis due to ineffective therapies and multiple resistance. Recent advance in understanding the microenvironment of cancer has significantly promoted the development of immunotherapy for advanced gastric cancer. Immunotherapy can induce immune responses in gastric cancer patients thus leads to the destruction of cancer cells. In comparison of traditional therapy, immunotherapy has demonstrated robust efficacy and tolerable toxicity. Therefore, this novel strategy for treatment of advanced gastric cancer has gain increasingly popularity. In this review, we summarize recent progress of immunotherapy in advanced gastric cancer, such as immune check point inhibitors, adoptive cell therapy, VEGF inhibitors, cancer vaccines and CAR-T cell therapy. We highlight immunotherapies involved in clinical applications and discuss the existing challenges of current immunotherapies and promising strategies to overcome these limitations.
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Affiliation(s)
- Xin Jin
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, China
| | - Zhaorui Liu
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Dongxiao Yang
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Kai Yin
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Xusheng Chang
- Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
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