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Dou R, Zhu X, Liu X, Bao J, Jin R, Mao G, Yu H, Liu Y. Icariside II inhibits gastric cancer progression by suppressing the Wnt/β-catenin signaling pathway. Cytotechnology 2025; 77:106. [PMID: 40416998 PMCID: PMC12098252 DOI: 10.1007/s10616-025-00761-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 04/24/2025] [Indexed: 05/27/2025] Open
Abstract
Gastric cancer is one of the common malignant tumours in clinical practice with poor prognosis and high mortality. Icariside II is a single compound extracted from the traditional Chinese medicine Epimedium brevicornu Maxim, and it is also the main active ingredient of Epimedium brevicornu Maxim that exerts pharmacological effects. Studies have shown that Icariside II has anti-tumour activity, but its mechanism of action on gastric cancer cells is unclear. This study aims to analyze the impact of Icariside II on gastric cancer cells as well as on xenograft tumor models of gastric cancer, and to examine the potential molecular regulatory pathways. GES-1, a normal gastric cell line, and gastric cancer cell lines AGS and MGC803 were cultured to investigate the cytotoxic effects of Icariside II using the methylthiazolyldiphenyl-tetrazolium (MTT). Flow cytometry (FCM) was employed to measure the impact of Icariside II on the apoptosis levels of gastric cancer cells, while western blot analysis was used to examine the expression of apoptosis-related proteins and the Wnt/β-catenin signaling pathway. Subsequently, a xenograft tumor model was established and treated with Icariside II to observe changes in tumor volume and weight in the model mice. Finally, alterations in the expression of the Wnt/β-catenin signaling pathway were assessed through immunofluorescence (IF) and immunohistochemistry (IHC). The results showed that Icariside II had faint significant toxic effect on GES-1 cells, and was able to inhibit the proliferative activity and promote apoptosis of the gastric cancer cells. Moreover, Icariside II was able to inhibit the growth of gastric cancer in nude mice subcutaneous transplantation tumor. In addition, both in vivo and in vitro results indicated that Icariside II inhibited the activation of the Wnt/β-catenin signaling pathway. Icariside II inhibited tumorigenicity of gastric cancer by suppressing the Wnt/β-catenin signaling.
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Affiliation(s)
- Rongrong Dou
- Department of Pathology and Pathophysiology, Medical School of Nantong University, Nantong, 226001 China
- Department of Pathology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, 225300 China
| | - Xiaowei Zhu
- Department of Pathology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, 225300 China
| | - Xinyun Liu
- Department of Pathology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, 225300 China
| | - Jingjing Bao
- Department of Pathology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, 225300 China
| | - Rongrong Jin
- Department of Pathology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, 225300 China
| | - Guangyao Mao
- Central laboratory, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, 225300 China
| | - Hong Yu
- Department of Pathology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, 225300 China
| | - Yifei Liu
- Department of Pathology, Affiliated Hospital of Nantong University, Nantong, 226001 China
- Medical School of Nantong University, Nantong, China
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Samalin E, Evesque L, Turpin A, De La Fouchardiere C, Khemissa-Akouz F, Bouché O, Muller M, Dermeche S, Botsen D, Tougeron D, Zaanan A, Ben Abdelghani M, Guardiola E, Dubreuil O, Le Brun Ly V, Hennequin A, Watson S, Sefrioui D, Lecomte T, De Sousa Carvalho N, Hulin A, Crapez E, Castan F, Senellart H. Regorafenib combined with irinotecan as second-line treatment in metastatic gastro-oesophageal adenocarcinomas: results of PRODIGE 58-UCGI35-REGIRI Unicancer randomised phase II study. ESMO Open 2025; 10:105096. [PMID: 40359707 DOI: 10.1016/j.esmoop.2025.105096] [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: 11/12/2024] [Revised: 03/13/2025] [Accepted: 04/07/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Several options have been evaluated in metastatic gastro-oesophageal adenocarcinomas (mGA) after failure of first-line fluoropyrimidine and platinum-based chemotherapy. Regorafenib (REGO), a receptor tyrosine kinase inhibitor, has shown promising activity as second- and third-line treatment of mGA. PATIENTS AND METHODS PRODIGE58-UCGI35-REGIRI was a comparative, prospective, phase II, open-label study evaluating the safety and efficacy of REGO [160 mg/day on day 2 (D2)-D8/D16-D22] plus irinotecan (IRI: 180 mg/m2 intravenously on D1/D15 every 28 days) versus IRI alone in patients with mGA (gastric or gastro-oesophageal junction/tumour Siewert II and III) after failure of first-line fluoropyrimidine and platinum-based chemotherapy. Primary endpoint was overall survival (OS). RESULTS Forty-four patients were included in the REGIRI arm and 45 in the IRI arm, primary tumours (67.4%) were mainly localised in the gastro-oesophageal junction, and 60.7% patients had synchronous metastases. With a median follow-up of 19.4 months [95% confidence interval (CI) 16.8-29.9 months], median OS was 6.3 months (95% CI 5.2-7.1 months) versus 8.2 months (95% CI 5.2-9.7 months) in the REGIRI versus IRI arms (hazard ratio 1.11, 95% CI 0.70-1.74, P = 0.66). Median progression-free survival was 2.2 months versus 1.9 months, objective response rate 15.9% versus 13.3%, and disease control rate 45.5% versus 33.3%. Grade 3 treatment-related adverse events (AEs) were reported for 52.3% of patients in the REGIRI arm versus 23.3% in the IRI arm with four toxic deaths (two homozygous UGT1A1∗28 patients died from sepsis and thrombotic microangiopathy, and two heterozygous UGT1A1∗1/∗28 patients from diarrhoea and pulmonary embolism), versus one (UGT1A1∗1 wild-type patient died from primary tumour perforation). Main grade ≥3 AEs were diarrhoea (18.2% versus 7.0%), hypertension (9.1% versus 0.0%), asthenia (6.8% versus 0.0%), febrile neutropenia (6.8% versus 0.0%), neutropenia (6.8% versus 11.6%), and weight decrease (6.8% versus 0.0%). CONCLUSIONS The study was stopped early because of limited efficacy and increased toxicities in the REGIRI arm, possibly due to drug interactions. No optimal sub-population that could benefit from a REGIRI regimen exposure was identified.
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Affiliation(s)
- E Samalin
- ICM, Department of Medical Oncology, Université de Montpellier, Montpellier, France.
| | - L Evesque
- Centre Antoine Lacassagne, Nice, France
| | - A Turpin
- Department of Medical Oncology, CHRU Lille, Lille, France; CNRS INSERM UMR9020-U1277, CANTHER Cancer Heterogeneity Plasticity and Resistance to Therapies, Université de Lille, Lille, France
| | | | | | | | - M Muller
- CHRU de Nancy, Vandoeuvre-Les-Nancy, France
| | - S Dermeche
- Institut Paoli Calmettes, Marseille, France
| | - D Botsen
- Department of Medical Oncology, Institut Godinot, Reims, France
| | | | - A Zaanan
- Hôpital Européen George Pompidou, Paris, France
| | | | - E Guardiola
- Centre de Cancérologie du Grand Montpellier, Montpellier, France
| | | | | | - A Hennequin
- Centre Georges François Leclerc, Dijon, France
| | | | | | - T Lecomte
- CHRU Tours-Hôpital Trousseau, Chambray-lès-Tours, France
| | | | - A Hulin
- APHP, GH H Mondor, Créteil, France
| | - E Crapez
- ICM, Translational Research Unit, Montpellier, France
| | - F Castan
- ICM, Department of Medical Oncology, Université de Montpellier, Montpellier, France
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Ji HS. Research and analysis of circulating tumor cell detection in the diagnosis and treatment of gastric cancer. World J Gastrointest Oncol 2025; 17:102329. [PMID: 40092958 PMCID: PMC11866229 DOI: 10.4251/wjgo.v17.i3.102329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 11/27/2024] [Accepted: 12/30/2024] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Circulating tumor cells (CTCs) are crucial for improving our knowledge regarding tumor progress, prognosis, and recurrence possibility. AIM To evaluate the role of CTCs in the early diagnosis and treatment of gastric cancer. METHODS From June 2020 to December 2021, a randomized study was conducted in our institution involving 80 patients scheduled for surgery for gastric cancer. The patients were divided into two groups: A control group that was tested for traditional serum markers and a study group that was assessed for serum CTCs. RESULTS In the study cohort, CTC levels did not correlate significantly with patient age, gender, or degree of tumor differentiation (P > 0.05). However, there was a significant correlation with the tumor-node-metastasis stage of the tumor (P < 0.05). In the study group, the CTC diagnostic positivity rate was 62.50% (25 out of 40 patients), while the positivity rate for conventional serum markers in the control group was 47.50% (19 out of 40 patients). The positive detection rate in the study group was significantly higher than that of the control group (P < 0.05). CONCLUSION CTCs have slight invasion and high sensitivity and specificity, presenting great value for early clinical diagnosis of recurrence and metastasis. It will improve the deceleration of disease development and increase the survival rate.
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Affiliation(s)
- Han-Shu Ji
- Second Department of General Surgery, Cangzhou Central Hospital, Cangzhou 061000, Hebei Province, China
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Hu Y, Zhang Y, Ding M, Xu R. HOXA10-AS Enhances Gastric Cancer Cell Proliferation, Migration, and Invasion via the p38 MAPK/STAT3 Signaling Pathway. J Biochem Mol Toxicol 2025; 39:e70187. [PMID: 39987516 DOI: 10.1002/jbt.70187] [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: 09/29/2024] [Revised: 01/11/2025] [Accepted: 02/08/2025] [Indexed: 02/25/2025]
Abstract
Gastric cancer (GC) represents a major global health concern, with over 1 million new cases diagnosed annually worldwide. Emerging studies have highlighted the significant correlation between long noncoding RNAs (lncRNAs) and the progression of GC. The objective of the current study is to investigate the roles and mechanism of lncRNA homeobox A10 antisense RNA (HOXA10-AS) in modulating malignant properties of GC cells. RT-qPCR was employed to detect HOXA10-AS expression in GC cells or human normal gastric epithelium cells. The cellular localization of HOXA10-AS and mRNA HOXA10 were detected using RNA fractionation assays. Colony forming assays and Transwell assays were performed to assess the proliferative, invasive, and migratory capabilities of GC cells. Western blot analysis was used to determine protein levels of epithelial mesenchymal transition (EMT) markers in GC cells. RNA immunoprecipitation, RNA pulldown assays and luciferase assays were conducted to explore gene interaction. As shown by experimental results, HOXA10-AS showed high expression in GC cells. The silencing of HOXA10-AS led to weakened proliferative, invasive, and migratory abilities of GC cells, as well as inhibition of the EMT process. Moreover, HOXA10-AS positively regulated HOXA10 expression by interacting with miR-29a/b/c-3p. Additionally, overexpression of HOXA10 counteracted the repressive impacts on malignant cellular process caused by the knockdown of HOXA10-AS. Furthermore, HOXA10-AS activated the p38 MAPK/STAT3 signaling pathway via upregulation of HOXA10. In conclusion, HOXA10-AS upregulates HOXA10 expression through interaction with miR-29a/b/c-3p. The resultant increase in HOXA10 expression activates the p38 MAPK/STAT3 signaling, thereby promoting GC cell growth, migration, invasion, and EMT process.
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Affiliation(s)
- Yu Hu
- Department of Pathology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Ying Zhang
- Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Meng Ding
- Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Ruisi Xu
- Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, China
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Liu Y, Huang T, Wang L, Wang Y, Liu Y, Bai J, Wen X, Li Y, Long K, Zhang H. Traditional Chinese Medicine in the treatment of chronic atrophic gastritis, precancerous lesions and gastric cancer. JOURNAL OF ETHNOPHARMACOLOGY 2025; 337:118812. [PMID: 39260710 DOI: 10.1016/j.jep.2024.118812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 08/27/2024] [Accepted: 09/07/2024] [Indexed: 09/13/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Chronic atrophic gastritis (CAG), precancerous lesions of gastric cancer (PLGC), and gastric cancer (GC), seriously threaten human health. Traditional Chinese medicine (TCM) has been employed in the treatment of chronic diseases for a long time and has shown remarkable efficacy. AIM OF THE STUDY Recently, there has been an increasing use of TCM in treating CAG, PLGC, and GC. The objective of this study is to compile a comprehensive overview of the existing research on the effects and molecular mechanisms of TCM, including formulas, single herbs, and active components. MATERIALS AND METHODS To obtain a comprehensive understanding of traditional use of TCM in treating these diseases, we reviewed ancient books and Chinese literature. In addition, keywords such as "TCM", "CAG", "PLGC", "GC", and "active ingredients" were used to collect modern research on TCM published in databases such as CNKI, Web of Science, and Pubmed up to April 2024. All collected information was then summarized and analyzed. RESULTS This study analyzed 174 articles, which covered the research progress of 20 TCM formulas, 14 single herbs, and 50 active ingredients in treating CAG, PLGC, and GC. Sources, effects, and molecular mechanisms of the TCM were summarized. CONCLUSIONS This article reviews the progress of TCM in the management of CAG, PLGC, and GC, which will provide a foundation for the clinical application and further development of TCM.
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Affiliation(s)
- Yuxi Liu
- Shaanxi Academy of Traditional Chinese Medicine (Shaanxi Provincial Hospital of Chinese Medicine), No.4 Xihuamen, Xi'an, 710003, China.
| | - Tingting Huang
- Northwest University, No. 229 Taibai North Road, Xi'an, 710069, China.
| | - Lu Wang
- Shaanxi University of Chinese Medicine, Middle section of Century Avenue, Xianyang, 712046, China.
| | - Yuan Wang
- Shaanxi Academy of Traditional Chinese Medicine (Shaanxi Provincial Hospital of Chinese Medicine), No.4 Xihuamen, Xi'an, 710003, China.
| | - Yang Liu
- Shaanxi Academy of Traditional Chinese Medicine (Shaanxi Provincial Hospital of Chinese Medicine), No.4 Xihuamen, Xi'an, 710003, China.
| | - Jingyi Bai
- Shaanxi Academy of Traditional Chinese Medicine (Shaanxi Provincial Hospital of Chinese Medicine), No.4 Xihuamen, Xi'an, 710003, China.
| | - Xinli Wen
- Shaanxi Academy of Traditional Chinese Medicine (Shaanxi Provincial Hospital of Chinese Medicine), No.4 Xihuamen, Xi'an, 710003, China.
| | - Ye Li
- Shaanxi Academy of Traditional Chinese Medicine (Shaanxi Provincial Hospital of Chinese Medicine), No.4 Xihuamen, Xi'an, 710003, China.
| | - Kaihua Long
- Shaanxi Academy of Traditional Chinese Medicine (Shaanxi Provincial Hospital of Chinese Medicine), No.4 Xihuamen, Xi'an, 710003, China.
| | - Hong Zhang
- Shaanxi Academy of Traditional Chinese Medicine (Shaanxi Provincial Hospital of Chinese Medicine), No.4 Xihuamen, Xi'an, 710003, China; Northwest University, No. 229 Taibai North Road, Xi'an, 710069, China; Shaanxi University of Chinese Medicine, Middle section of Century Avenue, Xianyang, 712046, China.
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Niu P, Zhang F, Ma D, Zhou X, Zhu Y, Luan X, Zhao L, Wang W, Zhang X, Han X, He M, Guan Q, Li Y, Liu Y, Chen Y. Trends of older gastric cancer incidence, mortality, and survival in the highest gastric cancer risk area in China: 2010-2019 and prediction to 2024. BMC Public Health 2024; 24:2449. [PMID: 39251980 PMCID: PMC11382508 DOI: 10.1186/s12889-024-19944-2] [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: 12/24/2023] [Accepted: 08/29/2024] [Indexed: 09/11/2024] Open
Abstract
BACKGROUND Gastric cancer is a major health problem worldwide, with a high incidence among older adults. Given the aging overall population, it was crucial to understand the current burden and prospective trend of older gastric cancer. This study aimed to analyze the temporal trends of the incidence, mortality, and survival of older gastric cancer in the highest gastric cancer risk area in China from 2010 to 2019, and to predict the future burden of older gastric cancer up to 2024. METHODS The study was conducted in Gansu province, an area characterized by the highest gastric cancer incidence and mortality in China. The registration data of gastric cancer incidence and mortality from 2010 to 2019 were pooled from registries in the Gansu Cancer Registration System, while survival data were collected from the First Hospital of Lanzhou University, Lanzhou University Second Hospital, and Gansu Cancer Hospital. Chinese standard population in 2000 and the Segi's world standard population were applied to calculate the age-standardized rate. Joinpoint regression was used to analyze the average annual percentage change (AAPC) in cancer incidence and mortality. Autoregressive Integrated Moving Average (ARIMA) models were employed to generate forecasts for incidence and mortality from 2020 to 2024. RESULTS Based on registry data from 2010 to 2019, the incidence and mortality rates of gastric cancer among older adults remained stable. The incidence rates declined from 439.65 per 100,000 in 2010 to 330.40 per 100,000 in 2019, with an AAPC of -2.59% (95% confidence interval[CI], -5.14 to 0.04, P = 0.06). Similarly, the mortality rate changed from 366.98 per 100,000 in 2010 to 262.03 per 100,000 in 2019, with an AAPC of -2.55% (95% CI, -8.77-4.08%, P = 0.44). In the hospital-based cohort, the decline in survival rates was reported among older patients with gastric cancer in the highest gastric cancer risk area in China, with the 3-year overall survival (OS) decreasing from 58.5% (95% CI, 53.5-63.2%) in 2010 to 34.4% (95%CI, 32.1-36.7%) in 2019, and the 3-year progression-free survival (PFS) decreasing from 51.3% (95%CI, 47.5-55.1%) in 2010 to 34.2% (95%CI, 32.0-36.3%) in 2019, respectively. Moreover, forecasts generated by ARIMA models revealed a significant decline in the incidence and mortality of older gastric cancer in China from 2020 to 2024. Specifically, the incidence rate of older gastric cancer was expected to decrease from 317.94 per 100,000 population in 2020 to 205.59 per 100,000 population in 2024, while the anticipated mortality rate was estimated to decrease from 222.52 per 100,000 population in 2020 to 186.22 per 100,000 population in 2024. CONCLUSION From 2010 to 2019, the incidence and mortality of older gastric cancer remained stable in the highest gastric cancer risk area in China, while the survival rates showed a decline. Based on the ARIMA models, it was anticipated that there might be a continued decline in older gastric cancer incidence and mortality in the highest-risk area in China over the next five years.
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Affiliation(s)
- Penghui Niu
- National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fan Zhang
- Lanzhou University Second Hospital, Lanzhou, China
| | - Deyuan Ma
- The First Hospital of Lanzhou University, Lanzhou, China
| | - Xiadong Zhou
- Gansu Provincial Cancer Hospital, Lanzhou, China
| | - Yitong Zhu
- Peking Union Medical College School of Population Medicine and Public Health, Beijing, China
| | - Xiaoyi Luan
- National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lulu Zhao
- National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wanqing Wang
- National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaojie Zhang
- Gastrointestinal Surgery Department, China-Japan Friendship Hospital, Beijing, China
| | - Xue Han
- National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Mingyan He
- Gansu Provincial Cancer Hospital, Lanzhou, China.
| | - Quanlin Guan
- The First Hospital of Lanzhou University, Lanzhou, China.
| | - Yumin Li
- Lanzhou University Second Hospital, Lanzhou, China.
| | - Yuqin Liu
- Gansu Provincial Cancer Hospital, Lanzhou, China.
| | - Yingtai Chen
- National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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Lu Z, Huang X, Shen Q, Chen E, Feng Y. Granzyme B Promotes Proliferation, Migration and EMT Process in Gastric Cancer. Biochem Genet 2024:10.1007/s10528-024-10841-2. [PMID: 38801462 DOI: 10.1007/s10528-024-10841-2] [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: 11/03/2023] [Accepted: 05/14/2024] [Indexed: 05/29/2024]
Abstract
Granzyme B (GZMB), a critical member of the Gr gene family, is known to play an essential role in diverse physiological and pathological processes such as inflammation, acute and chronic inflammatory diseases, and cancer progression. In this study, we delve deeper into the role of GZMB within the context of gastric cancer (GC) to examine its expression patterns and functional implications. To accomplish this, we applied a combination of quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry techniques. These methodologies allowed us to accurately gauge GZMB expression levels in GC tissues and investigate their correlation with various clinical-pathological variables. Our secondary focus was to discern the regulatory influence of GZMB on GC cell biology. We used an array of assays including cell counting kit-8 (CCK-8), colony formation, 5-ethynyl-2'-deoxyuridine, and migration assays. The effect of GZMB on gastric cancer progression was further validated through a subcutaneous xenograft mouse model. Our findings underscored that GZMB mRNA and protein levels were upregulated in GC tissues, a feature that showed a significant correlation with GC staging. We also discovered that a decrease in GZMB expression via knockdown experiments suppressed the proliferation and migration capabilities of GC cells. This effect was manifested through diminished expression levels of epithelial-mesenchymal transition (EMT) markers. In stark contrast, the overexpression of GZMB through plasmid transfection appeared to enhance the proliferation and migration abilities of GC cells. This was coupled with an upregulation in EMT expression. Our study concludes by emphasizing that GZMB promotes the growth, migration, and EMT processes in gastric cancer. In vitro, cell-based experiments and in vivo xenograft mouse models confirm this. Our findings provide a more comprehensive understanding of GZMB's role in gastric cancer pathogenesis, potentially opening doors for novel therapeutic strategies targeting this molecular pathway.
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Affiliation(s)
- Zhou Lu
- Department of Gastrointestinal Surgery, Medical School of Nantong University, Affiliated Hospital of Nantong University, Nantong, 226001, China
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 20 Xisi Street, Nantong, 226001, Jiangsu, China
| | - Xinkun Huang
- Department of General Surgery, Nantong Tumor Hospital and Affiliated Tumor Hospital of Nantong University, Nantong, 226361, China
| | - Qicheng Shen
- Department of Gastrointestinal Surgery, Medical School of Nantong University, Affiliated Hospital of Nantong University, Nantong, 226001, China
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 20 Xisi Street, Nantong, 226001, Jiangsu, China
| | - Erlin Chen
- Department of Gastrointestinal Surgery, Medical School of Nantong University, Affiliated Hospital of Nantong University, Nantong, 226001, China
| | - Ying Feng
- Department of Gastrointestinal Surgery, Medical School of Nantong University, Affiliated Hospital of Nantong University, Nantong, 226001, China.
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Ren F, Ma Y, Zhang K, Luo Y, Pan R, Zhang J, Kan C, Hou N, Han F, Sun X. Exploring the multi-targeting phytoestrogen potential of Calycosin for cancer treatment: A review. Medicine (Baltimore) 2024; 103:e38023. [PMID: 38701310 PMCID: PMC11062656 DOI: 10.1097/md.0000000000038023] [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: 07/30/2023] [Accepted: 04/05/2024] [Indexed: 05/05/2024] Open
Abstract
Cancer remains a significant challenge in the field of oncology, with the search for novel and effective treatments ongoing. Calycosin (CA), a phytoestrogen derived from traditional Chinese medicine, has garnered attention as a promising candidate. With its high targeting and low toxicity profile, CA has demonstrated medicinal potential across various diseases, including cancers, inflammation, and cardiovascular disease. Studies have revealed that CA possesses inhibitory effects against a diverse array of cancers. The underlying mechanism of action involves a reduction in tumor cell proliferation, induction of tumor cell apoptosis, and suppression of tumor cell migration and invasion. Furthermore, CA has been shown to enhance the efficacy of certain chemotherapeutic drugs, making it a potential component in treating malignant tumors. Given its high efficacy, low toxicity, and multi-targeting characteristics, CA holds considerable promise as a therapeutic agent for cancer treatment. The objective of this review is to present a synthesis of the current understanding of the antitumor mechanism of CA and its research progress.
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Affiliation(s)
- Fangbing Ren
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
- Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Yanhui Ma
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
- Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Kexin Zhang
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Youhong Luo
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Ruiyan Pan
- School of Pharmacy, Weifang Medical University, Weifang, China
| | - Jingwen Zhang
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Chengxia Kan
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Ningning Hou
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Fang Han
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
- Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Xiaodong Sun
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
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Xu J, Wang Y, Li X, Zheng M, Li Y, Zhang W. Clinical value assessment for serum hsa_tsr013526 in the diagnosis of gastric carcinoma. ENVIRONMENTAL TOXICOLOGY 2024; 39:2753-2767. [PMID: 38251933 DOI: 10.1002/tox.24146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 12/29/2023] [Accepted: 01/06/2024] [Indexed: 01/23/2024]
Abstract
Gastric carcinoma (GC) is a malignant tumor that is detrimental to human health. Transfer RNA-derived small RNAs are a newly identified class of noncoding small RNAs with specific biological functions that are aberrantly expressed in cancer. The aim of this study was to investigate the potential of hsa_tsr013526 as a biomarker for GC. Quantitative real-time fluorescence polymerase chain reaction was used to detect the expression level of hsa_tsr013526. The molecular characteristics of hsa_tsr013526 were verified by agarose gel electrophoresis, Sanger sequencing, and separation of nuclear and cytoplasmic RNA fractions. By testing the receiver operating characteristic (ROC) curves, the diagnostic efficiency of GC using hsa_tsr013526 was determined. Finally, we predicted the downstream of hsa_tsr013526 using functional assays and bioinformatics analysis. Serum expression of hsa_tsr013526 was higher in GC patients than in healthy donors. Serum expression showed differential changes in GC patients, gastritis patients, and healthy donors. Chi-squared tests showed that high expression of hsa_tsr013526 was significantly correlated with T stage, lymphatic metastasis, and tumor node metastasis stage. ROC curve analysis indicated that GC patients could be discriminated from healthy donors or gastritis patients based on their serum levels of hsa_tsr013526. Furthermore, hsa_tsr013526 expression was significantly reduced in postoperative GC patients (p = .0016). High expression of hsa_tsr013526 promotes gastric cancer cell proliferation, invasion, and migration. Serum hsa_tsr013526 was stable and specific, and could be used for dynamic monitoring of GC patients. Therefore, hsa_tsr013526 may be a new biomarker for the diagnosis and postoperative monitoring of GC patients.
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Affiliation(s)
- Jing Xu
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China
- Medical School, Nantong University, Nantong, China
| | - Yue Wang
- Basic Medicine School, Xuzhou Medical University, Xuzhou, China
| | - Xian Li
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Ming Zheng
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Yang Li
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China
- Medical School, Nantong University, Nantong, China
| | - Weiwei Zhang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China
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10
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Morgos DT, Stefani C, Miricescu D, Greabu M, Stanciu S, Nica S, Stanescu-Spinu II, Balan DG, Balcangiu-Stroescu AE, Coculescu EC, Georgescu DE, Nica RI. Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer. Int J Mol Sci 2024; 25:1848. [PMID: 38339127 PMCID: PMC10856016 DOI: 10.3390/ijms25031848] [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: 12/21/2023] [Revised: 01/26/2024] [Accepted: 01/31/2024] [Indexed: 02/12/2024] Open
Abstract
Gastric cancer (GC) is the fourth leading cause of death worldwide, with more than 1 million cases diagnosed every year. Helicobacter pylori represents the main risk factor, being responsible for 78% of the cases. Increased amounts of salt, pickled food, red meat, alcohol, smoked food, and refined sugars negatively affect the stomach wall, contributing to GC development. Several gene mutations, including PIK3CA, TP53, ARID1A, CDH1, Ras, Raf, and ERBB3 are encountered in GC pathogenesis, leading to phosphatidylinositol 3-kinase (PI3K) protein kinase B (AKT)/mammalian target of rapamycin (mTOR)-PI3K/AKT/mTOR-and mitogen-activated protein kinase (MAPK) signaling pathway activation and promoting tumoral activity. Helicobacter pylori, growth factors, cytokines, hormones, and oxidative stress also activate both pathways, enhancing GC development. In clinical trials, promising results have come from monoclonal antibodies such as trastuzumab and ramucirumab. Dual inhibitors targeting the PI3K/AKT/mTOR and MAPK signaling pathways were used in vitro studies, also with promising results. The main aim of this review is to present GC incidence and risk factors and the dysregulations of the two protein kinase complexes together with their specific inhibitors.
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Affiliation(s)
- Diana-Theodora Morgos
- Discipline of Anatomy, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Constantin Stefani
- Department I of Family Medicine and Clinical Base, “Dr. Carol Davila” Central Military Emergency University Hospital, 010825 Bucharest, Romania
| | - Daniela Miricescu
- Discipline of Biochemistry, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Maria Greabu
- Discipline of Biochemistry, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Silviu Stanciu
- Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacy, Central Military Emergency University Hospital, 010825 Bucharest, Romania;
| | - Silvia Nica
- Emergency Discipline, University Hospital of Bucharest, 050098 Bucharest, Romania;
| | - Iulia-Ioana Stanescu-Spinu
- Discipline of Physiology, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (I.-I.S.-S.); (D.G.B.); (A.-E.B.-S.)
| | - Daniela Gabriela Balan
- Discipline of Physiology, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (I.-I.S.-S.); (D.G.B.); (A.-E.B.-S.)
| | - Andra-Elena Balcangiu-Stroescu
- Discipline of Physiology, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (I.-I.S.-S.); (D.G.B.); (A.-E.B.-S.)
| | - Elena-Claudia Coculescu
- Discipline of Oral Pathology, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania;
| | - Dragos-Eugen Georgescu
- Department of General Surgery, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 50474 Bucharest, Romania;
- Department of General Surgery, “Dr. Ion Cantacuzino” Clinical Hospital, 020475 Bucharest, Romania
| | - Remus Iulian Nica
- Central Military Emergency University Hospital “Dr. Carol Davila”, 010825 Bucharest, Romania;
- Discipline of General Surgery, Faculty of Midwifery and Nursing, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
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11
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Ferreira AI, Lima Capela T, Macedo Silva V, Xavier S, Boal Carvalho P, Magalhães J, Cotter J. Gastric dysplasia in random biopsies: the influence of Helicobacter pylori infection and alcohol consumption in the presence of a lesion. Scand J Gastroenterol 2024; 59:125-132. [PMID: 37872792 DOI: 10.1080/00365521.2023.2272563] [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: 06/06/2023] [Revised: 08/09/2023] [Accepted: 10/14/2023] [Indexed: 10/25/2023]
Abstract
BACKGROUND Gastric dysplasia in the absence of an endoscopically defined lesion is rare, usually either a false positive diagnosis or a previously unidentified precancerous lesion during esophagogastroduodenoscopy (EGD). AIMS Evaluate factors associated with the presence of an endoscopically visible lesion during follow-up in patients with histologic diagnosis of gastric dysplasia in random biopsies. METHODS Retrospective cohort study including patients referred to our institution for gastric dysplasia in random biopsies during Index EGD. Endoscopic evaluation was performed with a high-definition endoscope using narrow band imaging (HD EGD-0). If no lesion was detected, endoscopic surveillance (HD EGD-FU) was conducted within 6 months for high grade dysplasia (HGD) or 12 months for low grade (LGD) or indefinite for dysplasia (IFD). RESULTS From a total sample of 96 patients, 5 (5.2%) presented with an endoscopically visible lesion during HD EGD-0, while 10 lesions (10.4%) were identified during HD EGD-FU. Patients with Helicobacter pylori infection at Index EDG and with regular alcohol consumption (≥25 g/day) were 8 and 4 times more likely to have an endoscopically visible lesion on HD EGD-FU (p = 0.012 and p = 0.047). In binary logistic regression, both factors were independent predictors of the presence of gastric lesion on HD EGD-FU (OR 9.284, p = 0.009 and OR 5.025, p = 0.033). CONCLUSIONS The presence of an endoscopically visible lesion after the histologic diagnosis of gastric dysplasia in random biopsies was more frequent during HD EGD-FU. H. pylori infection at Index EGD and regular alcohol consumption were significant predictors of the presence of gastric lesion on HD EGD-FU.
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Affiliation(s)
- Ana Isabel Ferreira
- Gastroenterology Department, Hospital Senhora da Oliveira, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Guimarães, Braga, Portugal
| | - Tiago Lima Capela
- Gastroenterology Department, Hospital Senhora da Oliveira, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Guimarães, Braga, Portugal
| | - Vítor Macedo Silva
- Gastroenterology Department, Hospital Senhora da Oliveira, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Guimarães, Braga, Portugal
| | - Sofia Xavier
- Gastroenterology Department, Hospital Senhora da Oliveira, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Guimarães, Braga, Portugal
| | - Pedro Boal Carvalho
- Gastroenterology Department, Hospital Senhora da Oliveira, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Guimarães, Braga, Portugal
| | - Joana Magalhães
- Gastroenterology Department, Hospital Senhora da Oliveira, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Guimarães, Braga, Portugal
| | - José Cotter
- Gastroenterology Department, Hospital Senhora da Oliveira, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Guimarães, Braga, Portugal
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12
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Xiong M, Yu C, Ren B, Zhong M, Peng Q, Zeng M, Song H. Global knowledge mapping and emerging trends in Helicobacter pylori-related precancerous lesions of gastric cancer research: A bibliometric analysis from 2013 to 2023. Medicine (Baltimore) 2023; 102:e36445. [PMID: 38050286 PMCID: PMC10695611 DOI: 10.1097/md.0000000000036445] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Accepted: 11/13/2023] [Indexed: 12/06/2023] Open
Abstract
Helicobacter pylori (H pylori) infection is a crucial element in chronic gastritis progression towards precancerous lesions of gastric cancer (PLGC) formation and, potentially, gastric cancer; however, screening for and eliminating H pylori has several challenges. This study aimed to assess the present research status, prominent themes, and frontiers of H pylori-related PLGC and to provide impartial evaluations of the developmental trends in this domain. This study extracted articles and review papers concerning H pylori-related PLGC published from 2013 to 2023 from the Web of Science Core Collection. The data was analyzed and visualized using VOSviewer and CiteSpace. The study encompassed 1426 papers, with a discernible upward trend in publications between 2013 and 2023. China emerged as the most productive country, whereas the United States exerted the greatest influence. Baylor College of Medicine was the most prolific institution. World Journal of Gastroenterology featured the highest number of published papers, whereas Gastroenterology was the most frequently cited journal. Kim N. from South Korea was the most prolific author. Co-cited literature pertained to various aspects such as gastritis classification, H pylori infection management, gastric cancer prevention, and managing patients with PLGC. Future research will focus on the Kyoto classification, cancer incidence, and gastric intestinal metaplasia. The results of this study indicate a persistent increase in attention directed toward H pylori-associated PLGC. The research emphasis has transitioned from molecular mechanisms, epidemiology, monitoring, and diagnosis to clinical prevention and treatment methodologies. The forthcoming research direction in this area will concentrate on controlling and preventing malignant PLGC transformation.
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Affiliation(s)
- Meng Xiong
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, China
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Chang Yu
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, China
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Baoping Ren
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, China
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Meiqi Zhong
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, China
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Qinghua Peng
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, China
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Meiyan Zeng
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Houpan Song
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, China
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
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De Marco K, Lepore Signorile M, Di Nicola E, Sanese P, Fasano C, Forte G, Disciglio V, Pantaleo A, Varchi G, Del Rio A, Grossi V, Simone C. SMYD3 Modulates the HGF/MET Signaling Pathway in Gastric Cancer. Cells 2023; 12:2481. [PMID: 37887325 PMCID: PMC10605494 DOI: 10.3390/cells12202481] [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: 07/25/2023] [Revised: 10/11/2023] [Accepted: 10/13/2023] [Indexed: 10/28/2023] Open
Abstract
Gastric cancer (GC) is the third most deadly cancer worldwide. Considerable efforts have been made to find targetable drivers in order to improve patient outcomes. MET is one of the most important factors involved in GC initiation and progression as it plays a major role in GC invasiveness and is related to cancer stemness. Unfortunately, treatment strategies targeting MET are still limited, with a proportion of patients responding to therapy but later developing resistance. Here, we showed that MET is a molecular partner of the SMYD3 methyltransferase in GC cells. Moreover, we found that SMYD3 pharmacological inhibition affects the HGF/MET downstream signaling pathway. Extensive cellular analyses in GC models indicated that EM127, a novel active site-selective covalent SMYD3 inhibitor, can be used as part of a synergistic approach with MET inhibitors in order to enhance the targeting of the HGF/MET pathway. Importantly, our data were confirmed in a 3D GC cell culture system, which was used as a surrogate to evaluate stemness characteristics. Our findings identify SMYD3 as a promising therapeutic target to impair the HGF/MET pathway for the treatment of GC.
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Affiliation(s)
- Katia De Marco
- Medical Genetics, National Institute for Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, 70013 Castellana Grotte, Italy; (K.D.M.); (M.L.S.); (E.D.N.); (P.S.); (C.F.); (G.F.); (V.D.); (A.P.)
| | - Martina Lepore Signorile
- Medical Genetics, National Institute for Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, 70013 Castellana Grotte, Italy; (K.D.M.); (M.L.S.); (E.D.N.); (P.S.); (C.F.); (G.F.); (V.D.); (A.P.)
| | - Elisabetta Di Nicola
- Medical Genetics, National Institute for Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, 70013 Castellana Grotte, Italy; (K.D.M.); (M.L.S.); (E.D.N.); (P.S.); (C.F.); (G.F.); (V.D.); (A.P.)
| | - Paola Sanese
- Medical Genetics, National Institute for Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, 70013 Castellana Grotte, Italy; (K.D.M.); (M.L.S.); (E.D.N.); (P.S.); (C.F.); (G.F.); (V.D.); (A.P.)
| | - Candida Fasano
- Medical Genetics, National Institute for Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, 70013 Castellana Grotte, Italy; (K.D.M.); (M.L.S.); (E.D.N.); (P.S.); (C.F.); (G.F.); (V.D.); (A.P.)
| | - Giovanna Forte
- Medical Genetics, National Institute for Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, 70013 Castellana Grotte, Italy; (K.D.M.); (M.L.S.); (E.D.N.); (P.S.); (C.F.); (G.F.); (V.D.); (A.P.)
| | - Vittoria Disciglio
- Medical Genetics, National Institute for Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, 70013 Castellana Grotte, Italy; (K.D.M.); (M.L.S.); (E.D.N.); (P.S.); (C.F.); (G.F.); (V.D.); (A.P.)
| | - Antonino Pantaleo
- Medical Genetics, National Institute for Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, 70013 Castellana Grotte, Italy; (K.D.M.); (M.L.S.); (E.D.N.); (P.S.); (C.F.); (G.F.); (V.D.); (A.P.)
| | - Greta Varchi
- Institute for Organic Synthesis and Photoreactivity (ISOF), National Research Council of Italy (CNR), 40129 Bologna, Italy; (G.V.); (A.D.R.)
| | - Alberto Del Rio
- Institute for Organic Synthesis and Photoreactivity (ISOF), National Research Council of Italy (CNR), 40129 Bologna, Italy; (G.V.); (A.D.R.)
- Innovamol Consulting Srl, 41126 Modena, Italy
| | - Valentina Grossi
- Medical Genetics, National Institute for Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, 70013 Castellana Grotte, Italy; (K.D.M.); (M.L.S.); (E.D.N.); (P.S.); (C.F.); (G.F.); (V.D.); (A.P.)
| | - Cristiano Simone
- Medical Genetics, National Institute for Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, 70013 Castellana Grotte, Italy; (K.D.M.); (M.L.S.); (E.D.N.); (P.S.); (C.F.); (G.F.); (V.D.); (A.P.)
- Medical Genetics, Department of Precision and Regenerative Medicine and Jonic Area (DiMePRe-J), University of Bari Aldo Moro, 70124 Bari, Italy
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14
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Sun C, Xu H, Wang S, Li K, Qin P, Liang B, Xu L. Lifestyle, clinical and histological indices-based prediction models for survival in cancer patients: a city-wide prospective cohort study in China. J Cancer Res Clin Oncol 2023; 149:9965-9978. [PMID: 37256382 DOI: 10.1007/s00432-023-04888-8] [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: 04/04/2023] [Accepted: 05/19/2023] [Indexed: 06/01/2023]
Abstract
PURPOSE We developed a nomogram to predict 3-year, 5-year and 7-year cancer survival rates of cancer patients. METHODS This prospective cohort study included 20,491 surviving patients first diagnosed with cancer in Guangzhou from 2010 to 2019. They were divided into a training and a validation group. Lifestyle, clinical and histological parameters (LCH) were included in multivariable Cox regression. Akaike information criterion was used to select prediction factors for the nomogram. The discrimination and calibration of models were assessed by concordance index (C-index), area under time-dependent receiver operating characteristic curve (time-dependent AUC), and calibration plots. We used net reclassification index (NRI) and integrated discrimination improvement (IDI) to compare the clinical utility of LCH prediction model with the prediction model based on lifestyle factors (LF). RESULTS 13 prediction factors including age, sex, BMI, smoking status, physical activity, sleep duration, regular diet, tumor grading, TNM stage, multiple primary cancer and anatomical site were included in the LCH model. The LCH model showed satisfactory discrimination and calibration (C-index = 0.81 (95% CI 0.80-0.82) for training group and 0.80 (0.79-0.81) for validation group, both time-dependent AUC > 0.70). The LF model including smoking status, physical activity, sleep duration, regular diet, and BMI showed less satisfactory discrimination (C-index = 0.60 (95% CI 0.59-0.61) for training and 0.60 (0.58-0.62) for validation group). The LCH model had better accuracy and discriminative ability than the LF model, as indicated by positive NRI and IDI values. CONCLUSIONS The LCH model shows good accuracy, clinical utility and precise prognosis prediction, and may serve as a tool to predict cancer survival of cancer patients.
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Affiliation(s)
- Ce Sun
- Department of Epidemiology, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China
| | - Huan Xu
- Chronic Noncommunicable Disease Prevention and Control Department, Guangzhou Center for Disease Control and Prevention, No.1 Qide Road, Baiyun District, Guangzhou, 510403, China
| | - Suixiang Wang
- Chronic Noncommunicable Disease Prevention and Control Department, Guangzhou Center for Disease Control and Prevention, No.1 Qide Road, Baiyun District, Guangzhou, 510403, China
| | - Ke Li
- The Operation Management Department, Guangzhou Center for Disease Control and Prevention, Guangzhou, 510403, China
| | - Pengzhe Qin
- Chronic Noncommunicable Disease Prevention and Control Department, Guangzhou Center for Disease Control and Prevention, No.1 Qide Road, Baiyun District, Guangzhou, 510403, China
| | - Boheng Liang
- Chronic Noncommunicable Disease Prevention and Control Department, Guangzhou Center for Disease Control and Prevention, No.1 Qide Road, Baiyun District, Guangzhou, 510403, China.
| | - Lin Xu
- Department of Epidemiology, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China.
- School of Public Health, University of Hong Kong, Hong Kong, China.
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15
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Li Y, Shen L, Tao K, Xu G, Ji K. Key Roles of p53 Signaling Pathway-Related Factors GADD45B and SERPINE1 in the Occurrence and Development of Gastric Cancer. Mediators Inflamm 2023; 2023:6368893. [PMID: 37662480 PMCID: PMC10471451 DOI: 10.1155/2023/6368893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 05/16/2023] [Accepted: 07/24/2023] [Indexed: 09/05/2023] Open
Abstract
p53 can function as an independent and unfavorable prognosis biomarker in cancer patients. We tried to identify the key factors of the p53 signaling pathway involved in gastric cancer (GC) occurrence and development based on the genotype-tissue expression (GTEx) and the Cancer Genome Atlas (TCGA) screening. We downloaded gene expression data and clinical data of GC included in the GTEx and TCGA databases, followed by differential analysis. Then, the key factors in the p53 signaling pathway were identified, followed by an analysis of the correlation between key factors and the prognosis of GC patients. Human GC cell lines were selected for in vitro cell experiments to verify the effects of key prognostic factors on the proliferation, migration, invasion, and apoptosis of GC cells. We found 4,944 significantly differentially expressed genes (DEGs), of which 2,465 were upregulated and 2,479 downregulated in GC. Then, 27 DEGs were found to be involved in the p53 signaling pathway. GADD45B and SERPINE1 genes were prognostic high-risk genes. The regression coefficients of GADD45B and SERPINE1 were positive. GADD45B was poorly expressed, while SERPINE1 was highly expressed in GC tissues, highlighting their prognostic role in GC. The in vitro cell experiments confirmed that overexpression of GADD45B or silencing of SERPINE1 could inhibit the proliferation, migration, and invasion and augment the apoptosis of GC cells. Collectively, the p53 signaling pathway-related factors GADD45B and SERPINE1 may be key genes that participate in the development of GC.
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Affiliation(s)
- Yaoqing Li
- Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing 312000, China
| | - Liyijing Shen
- Department of Radiology, Shaoxing People's Hospital, Shaoxing 312000, China
| | - Kelong Tao
- Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing 312000, China
| | - Guangen Xu
- Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing 312000, China
| | - Kewei Ji
- Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing 312000, China
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16
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Zhang Y, Sheng Z, Xiao J, Li Y, Huang J, Jia J, Zeng X, Li L. Advances in the roles of glycyrrhizic acid in cancer therapy. Front Pharmacol 2023; 14:1265172. [PMID: 37649893 PMCID: PMC10463042 DOI: 10.3389/fphar.2023.1265172] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Accepted: 08/07/2023] [Indexed: 09/01/2023] Open
Abstract
Since the first 70 years of reporting cancer chemotherapy, malignant tumors have been the second most common cause of death in children and adults. Currently, the commonly used anti-cancer methods include surgery, chemotherapy, radiotherapy, and immunotherapy. Although these treatment methods could alleviate cancer, they lead to different forms of side effects and have no particularly significant effect on prolonging the patients' life span. Glycyrrhizic acid (GL), a native Chinese herbal extract, has a wide range of pharmacological effects, such as anti-cancer, anti-inflammatory, antioxidant, and immune regulation. In this review, the anti-cancer effects and mechanisms of GL are summarized in various cancers. The inhibition of GL on chemotherapy-induced side effects, including hepatotoxicity, nephrotoxicity, genotoxicity, neurotoxicity and pulmonary toxicity, is highlighted. Therefore, GL may be a promising and ideal drug for cancer therapy.
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Affiliation(s)
- Yuqian Zhang
- Research Center of Neuroscience, Jiaxing University Medical College, Jiaxing, China
| | - Zixuan Sheng
- Research Center of Neuroscience, Jiaxing University Medical College, Jiaxing, China
| | - Jing Xiao
- Research Center of Neuroscience, Jiaxing University Medical College, Jiaxing, China
| | - Yang Li
- Research Center of Neuroscience, Jiaxing University Medical College, Jiaxing, China
| | - Jie Huang
- Research Center of Neuroscience, Jiaxing University Medical College, Jiaxing, China
| | - Jinjing Jia
- Research Center of Neuroscience, Jiaxing University Medical College, Jiaxing, China
- Department of Physiology, Jiaxing University Medical College, Jiaxing, China
| | - Xiansi Zeng
- Research Center of Neuroscience, Jiaxing University Medical College, Jiaxing, China
- Department of Biochemistry and Molecular Biology, Jiaxing University Medical College, Jiaxing, China
| | - Li Li
- Research Center of Neuroscience, Jiaxing University Medical College, Jiaxing, China
- Department of Physiology, Jiaxing University Medical College, Jiaxing, China
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17
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Li B, Shu X, Jiang H, Shi C, Qi L, Zhu L, Zhou J, Tang M, Hu A. Plasma metabolome identifies potential biomarkers of gastric precancerous lesions and gastric cancer risk. Metabolomics 2023; 19:73. [PMID: 37561286 DOI: 10.1007/s11306-023-02037-3] [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: 06/19/2023] [Accepted: 07/26/2023] [Indexed: 08/11/2023]
Abstract
OBJECTIVES Currently, metabolic biomarkers with great practicability of gastric cancer (GC) and gastric precancerous lesions (GPL) are scarce. Thus, we are devoted to determining the plasma metabolic profiles of patients with GPL or GC and validate candidate biomarkers for disease diagnosis. METHODS In this hospital-based case-control study, 68 plasma samples from 27 non-atrophic gastritis (NAG, control), 31 GPL, and 10 GC patients were collected for targeted metabolomics analysis. Univariate and multivariate analyses were used for selecting the differential metabolites. A receiver operating characteristic curve combined with binary logistic regression analysis was performed to test the diagnostic performance of the differential metabolites. Dietary data were obtained using a semiquantitative food frequency questionnaire. RESULTS Distinct metabolomic profiles were noted for NAG, GPL, and GC. Compared to the NAG patients, the levels of 5 metabolites in the GPL group and 4 metabolites in the GC group were found to significantly elevate. Compared with the model involving 9 traditional risk factors (AUC: 0.89, 95%CI: 0.78-1.00), Trimethylamine N-oxide, the most significant metabolite (P = 2.00 × 10-5, FDR = 0.003, FC > 2, VIP > 2), showed a good diagnostic performance for the patients with GC (AUC: 0.90, 95%CI: 0.78-1.00), and its diagnostic performance has been further improved with the integration of Rhamnose (AUC: 0.96, 95%CI: 0.89-1.00). CONCLUSION In our study, 9 defined metabolites might serve as meaningful biomarkers for identifying the high-risk population of GPL and GC, possibly enhancing the prevention and control of GPL and GC.
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Affiliation(s)
- Bin Li
- Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China
| | - Xing Shu
- Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China
| | - Haoqi Jiang
- Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China
| | - Change Shi
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Gastroenterology and Hepatology, Anhui Public Health Clinical Center, Hefei, China
| | - Le Qi
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Gastroenterology and Hepatology, Anhui Public Health Clinical Center, Hefei, China
| | - Lili Zhu
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Gastroenterology and Hepatology, Anhui Public Health Clinical Center, Hefei, China
| | - Juanyan Zhou
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Gastroenterology and Hepatology, Anhui Public Health Clinical Center, Hefei, China
| | - Min Tang
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
- Department of Gastroenterology and Hepatology, Anhui Public Health Clinical Center, Hefei, China.
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Anhui Medical University, Anhui Public Health Clinical Center, Hefei, China.
| | - Anla Hu
- Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China.
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Zhang H, Zhuo H, Hou J, Cai J. Machine learning models predict the mTOR signal pathway-related signature in the gastric cancer involving 2063 samples of 7 centers. Aging (Albany NY) 2023; 15:6152-6162. [PMID: 37341987 PMCID: PMC10373976 DOI: 10.18632/aging.204817] [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: 03/14/2023] [Accepted: 05/17/2023] [Indexed: 06/22/2023]
Abstract
Gastric cancer, as a tumor with poor prognosis, has been widely studied. Distinguishing the types of gastric cancer is helpful. Using the transcriptome data of gastric cancer in our study, relevant proteins of mTOR signaling pathway were screened to identify key genes by four machine learning models, and the models were validated in external datasets. Through correlation analysis, we explored the relationship between five key genes and immune cells and immunotherapy. By inducing cellular senescence in gastric cancer cells with bleomycin, we investigated changes in the expression levels of HRAS through western blot. By PCA clustering analysis, we used the five key genes for gastric cancer typing and explored differences in drug sensitivity and enrichment pathways between different clustering groups. We found that the SVM machine learning model was superior, and the five genes (PPARA, FNIP1, WNT5A, HRAS, HIF1A) were highly correlated with different immune cells in multiple databases. These five key genes have a significant impact on immunotherapy. Using the five genes for gastric cancer gene typing, four genes were expressed higher in group 1 and were more sensitive to drugs in group 2. These results suggest that subtype-specific markers can improve the treatment and provide precision drugs for gastric cancer patients.
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Affiliation(s)
- Hao Zhang
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian, China
- Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen 361004, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen 361004, Fujian, China
| | - Huiqin Zhuo
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian, China
- Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen 361004, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen 361004, Fujian, China
| | - Jingjing Hou
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian, China
- Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen 361004, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen 361004, Fujian, China
| | - Jianchun Cai
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian, China
- Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen 361004, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen 361004, Fujian, China
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19
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Chen S, Yu W, Li Z, Wang Y, Peng B. STYXL1 promotes proliferation and epithelial mesenchymal transition of gastric cancer cells via activating the PI3K/AKT pathway. Mol Cell Toxicol 2023. [DOI: 10.1007/s13273-023-00345-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/28/2023]
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20
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Ren L, Ren Q, Wang J, He Y, Deng H, Wang X, Liu C. miR-199a-3p promotes gastric cancer progression by promoting its stemness potential via DDR2 mediation. Cell Signal 2023; 106:110636. [PMID: 36813149 DOI: 10.1016/j.cellsig.2023.110636] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 02/04/2023] [Accepted: 02/17/2023] [Indexed: 02/22/2023]
Abstract
BACKGROUND Peritoneal metastasis (PM) is an independent prognostic factor in gastric cancer (GC), however, the underlying mechanisms of PM occurrence remain unclear. METHOD The roles of DDR2 were investigated in GC and its potential relationship to PM, and orthotopic implants into nude mice were performed to assess the biological effects of DDR2 on PM. RESULTS Herein, DDR2 level is more significantly observed to elevate in PM lesion than the primary lesion. GC with DDR2-high expression evokes a worse overall survival (OS) in TCGA, similar results of the gloomy OS with high DDR2 levels are clarified via the stratifying stage of TNM. The conspicuously increased expression of DDR2 was found in GC cell lines, luciferase reporter assays verified that miR-199a-3p directly targeted DDR2 gene, which was correlated to tumor progression. We ulteriorly observed DDR2 participated in GC stemness maintenance via mediating pluripotency factor SOX2 expression and implicated in autophagy and DNA damage of cancer stem cells (CSCs). In particular, DDR2 dominated EMT programming through recruiting NFATc1-SOX2 complex to Snai1 in governing cell progression, controlling by DDR2-mTOR-SOX2 axis in SGC-7901 CSCs. Furthermore, DDR2 promoted the tumor peritoneal dissemination in gastric xenograft mouse model. CONCLUSION Phenotype screens and disseminated verifications incriminating in GC exposit the miR-199a-3p-DDR2-mTOR-SOX2 axis as a clinically actionable target for tumor PM progression. The herein-reported DDR2-based underlying axis in GC represents novel and potent tools for studying the mechanisms of PM.
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Affiliation(s)
- Lei Ren
- Department of General Surgery (Gastrointestinal Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China; Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany
| | - Qiang Ren
- Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Jianmei Wang
- Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Yonghong He
- Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Hong Deng
- Department of General Surgery (Gastrointestinal Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Xing Wang
- Inflammation and Allergic Research Unit, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Chunfeng Liu
- Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China; Inflammation and Allergic Research Unit, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China; Experimental and Molecular Pathology, Institute of Pathology, Ludwig-Maximilians-University, Thalkirchner Str. 36, Munich 80336, Germany.
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21
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Yan C, Shan F, Ying X, Li Z. Global burden prediction of gastric cancer during demographic transition from 2020 to 2040. Chin Med J (Engl) 2023; 136:397-406. [PMID: 36877996 PMCID: PMC10106237 DOI: 10.1097/cm9.0000000000002626] [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: 01/15/2023] [Indexed: 03/08/2023] Open
Abstract
BACKGROUND Despite the decline in the incidence and mortality rates of gastric cancer (GC), the impact of demographic transition on the global burden of GC remains unclear. The current study aimed to estimate the global disease burden through 2040 by age, sex, and region. METHODS GC data for incident cases and deaths by age group and sex were taken from The Global Cancer Observatory (GLOBOCAN) 2020. The incidence and mortality rates were predicted through 2040 by fitting a linear regression model over the most recent trend period with the Cancer Incidence in Five Continents (CI5) data. RESULTS The global population will grow to 9.19 billion by 2040, accompanied by increasing population ageing. The incidence and mortality rates of GC will show a persistent decrease, with an annual percent change of -0.57% for males and -0.65% for females. East Asia and North America will have the highest and lowest age standardized rates, respectively. A slowdown in the growth of incident cases and deaths will be observed worldwide. The proportion of young and middle-aged individuals will decline, while the percentage of the elderly will increase, and the number of males will be almost twice the number of females. East Asia and high human development index (HDI) regions will be heavily burdened by GC. East Asia had 59.85% of the new cases and 56.23% of deaths in 2020; these will increase to 66.93% and 64.37% by 2040, respectively. The interaction between population growth, the change in ageing structure and the decline in incidence and mortality rates will lead to an increased burden of GC. CONCLUSIONS Ageing and population growth will offset the decline in the incidence and mortality rate of GC, resulting in a substantial increase in the number of new cases and deaths. The age structure will continue to change, especially in high HDI regions, requiring more targeted prevention strategies in the future.
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Affiliation(s)
- Chao Yan
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
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22
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Liang Y, Rao Z, Du D, Wang Y, Fang T. Butyrate prevents the migration and invasion, and aerobic glycolysis in gastric cancer via inhibiting Wnt/β-catenin/c-Myc signaling. Drug Dev Res 2023; 84:532-541. [PMID: 36782390 DOI: 10.1002/ddr.22043] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 01/10/2023] [Accepted: 01/19/2023] [Indexed: 02/15/2023]
Abstract
Gastric cancer (GC) remains a common cause of cancer death worldwide. Evidence has found that butyrate exhibited antitumor effects on GC cells. However, the mechanism by which butyrate regulate GC cell proliferation, migration, invasion, and aerobic glycolysis remains largely unknown. The proliferation, migration, and invasion of GC cells were tested by EdU staining, transwell assays. Additionally, protein expressions were determined by western blot assay. Next, glucose uptake, lactate production, and cellular ATP levels in GC cells were detected. Furthermore, the antitumor effects of butyrate in tumor-bearing nude mice were evaluated. We found, butyrate significantly prevented GC cell proliferation, migration, and invasion (p < .01). Additionally, butyrate markedly inhibited GC cell aerobic glycolysis, as shown by the reduced expressions of GLUT1, HK2, and LDHA (p < .01). Moreover, butyrate notably decreased nuclear β-catenin and c-Myc levels in GC cells (p < .01). Remarkably, through activating Wnt/β-catenin signaling with LiCl, the inhibitory effects of butyrate on the growth and aerobic glycolysis of GC cells were diminished (p < .01). Moreover, butyrate notably suppressed tumor volume and weight in GC cell xenograft nude mice in vivo (p < .01). Meanwhile, butyrate obviously reduced nuclear β-catenin, c-Myc, GLUT1, HK2 and LDHA levels in tumor tissues in GC cell xenograft mice (p < .01). Collectively, butyrate could suppress the growth and aerobic glycolysis of GC cells in vitro and in vivo via downregulating wnt/β-catenin/c-Myc signaling. These findings are likely to prove useful in better understanding the role of butyrate in GC.
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Affiliation(s)
- Yizhi Liang
- Department of Gastroenterology, The Second Affiliated Clinical Medical College of Fujian Medical University, The Second Affiliated Hospital of Fujian Medical University, Fujian, China
| | - Zilan Rao
- Department of Gastroenterology, The Second Affiliated Clinical Medical College of Fujian Medical University, The Second Affiliated Hospital of Fujian Medical University, Fujian, China
| | - Dongwei Du
- Department of Gastroenterology, The Second Affiliated Clinical Medical College of Fujian Medical University, The Second Affiliated Hospital of Fujian Medical University, Fujian, China
| | - Yiwen Wang
- Department of Gastroenterology, The Second Affiliated Clinical Medical College of Fujian Medical University, The Second Affiliated Hospital of Fujian Medical University, Fujian, China
| | - Taiyong Fang
- Department of Gastroenterology, The Second Affiliated Clinical Medical College of Fujian Medical University, The Second Affiliated Hospital of Fujian Medical University, Fujian, China
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23
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Naemi Kermanshahi M, Safaei E, Tutunchi H, Naghshi S, Mobarak S, Asadi M, Sadeghi O. Fruit and vegetable intake in relation to gastric cancer risk: A comprehensive and updated systematic review and dose-response meta-analysis of cohort studies. Front Nutr 2023; 10:973171. [PMID: 36814513 PMCID: PMC9939448 DOI: 10.3389/fnut.2023.973171] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Accepted: 01/04/2023] [Indexed: 02/08/2023] Open
Abstract
Background Since the release of previous meta-analyses, some studies on the associations between fruit and vegetable intake with gastric cancer risk have been published. Therefore, we aimed to update the previous meta-analyses on these associations by including recently published studies as well as considering the main limitations of those meta-analyses. Methods A comprehensive search was conducted in online databases including PubMed, Scopus, ISI Web of Science, and Google Scholar to detect relevant prospective cohort studies published up to October 2021. Summary relative risks (RRs) were estimated using a random-effects model. Results Overall, 17 articles containing 18 prospective studies with a total sample size of 1,527,995 participants, aged between 18 and 90 years, were included in the current meta-analysis. During the follow-up periods ranging between 4.5 and 21 years, 8,477 cases of gastric cancer were diagnosed. A higher intake of total fruit [RR: 0.87, 95% confidence interval (CI): 0.80 to 0.94, I 2 = 0%] and total fruit and vegetable (RR: 0.75, 95% CI: 0.61 to 0.93, I 2 = 55.2%) were associated with a lower risk of gastric cancer. For total vegetable intake, a significant inverse association was found among the studies that controlled their analysis for energy intake. Based on the linear dose-response analysis, each 100 g/day increase in total fruit intake (Pooled RR: 0.95, 95% CI: 0.90 to 0.99, I 2 = 49%) and 200 g/day increase in total fruit and vegetable intake (RR: 0.94, 95% CI: 0.88 to 0.99, I 2 = 37.6%) were associated with a 5 and 6% lower risk of gastric cancer, respectively. Conclusion Fruit and vegetable consumption has a protective association with gastric cancer risk.
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Affiliation(s)
- Mohammad Naemi Kermanshahi
- Student Research Committee, Nutrition Research Center, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ehsan Safaei
- Student Research Committee, Nutrition Research Center, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran,Nutrition Research Center, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Helda Tutunchi
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sina Naghshi
- Student Research Committee, Nutrition Research Center, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran,Nutrition Research Center, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sara Mobarak
- Abadan Faculty of Medical Sciences, Abadan, Iran
| | - Masoomeh Asadi
- Department of Operating Room Nursing, Abadan Faculty of Medical Sciences, Abadan, Iran,Masoomeh Asadi,
| | - Omid Sadeghi
- Nutrition and Food Security Research Center, Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran,Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran,*Correspondence: Omid Sadeghi,
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24
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Li P, Ji W, Wei Z, Wang X, Qiao G, Gao C, Wang Y, Qi F. Comprehensive analysis to identify pseudogenes/lncRNAs-hsa-miR-200b-3p-COL5A2 network as a prognostic biomarker in gastric cancer. Hereditas 2022; 159:43. [PMID: 36447214 PMCID: PMC9706917 DOI: 10.1186/s41065-022-00257-6] [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: 06/06/2022] [Accepted: 11/12/2022] [Indexed: 11/30/2022] Open
Abstract
OBJECTIVE Gastric cancer is one of the most common and deadly types of cancer. The molecular mechanism of gastric cancer progression remains unclear. MATERIALS AND METHODS Four hub genes were identified through GEO and TCGA database screening and analysis. Prognostic analysis revealed that COL5A2 was the most likely to affect the prognosis of gastric cancer among the four hub genes. The relationships between COL5A2 and clinical variables and immune cell infiltration were analyzed. Then, COL5A2 was analyzed for single-gene differences and related functional enrichment. Using the starBase database for prediction and analysis, miRNAs and pseudogenes/lncRNAs that might combine with COL5A2 were identified; thus, the ceRNA network was constructed. Finally, the network was verified by Cox analysis and qPCR, and a nomogram was constructed. RESULTS First, we found that COL5A2, COL12A1, BGN and THBS2 were highly expressed in gastric cancer. COL5A2 had statistical significance in overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) analysis. Immune infiltration analysis suggested that COL5A2 might influence the changes in the tumor immune microenvironment. The StarBase database was used to predict that 3 pseudogenes and 7 lncRNAs might inhibit the hsa-miR-200b-3p-COL5A2 axis in gastric cancer. The pseudogenes/lncRNA-hsa-miR-200b-3p-COL5A2 ceRNA network was identified and verified using Cox regression analysis and PCR. Finally, we constructed a nomogram. CONCLUSIONS We elucidated the regulatory role of the pseudogenes/lncRNA-hsa-miR-200b-3p-COL5A2 network in gastric cancer progression and constructed a nomogram. These studies may provide effective treatments and potential prognostic biomarkers for gastric cancer.
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Affiliation(s)
- Peiyuan Li
- grid.412645.00000 0004 1757 9434Department of General Surgery, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052 China
| | - Wenbin Ji
- grid.412645.00000 0004 1757 9434Department of General Surgery, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052 China
| | - Zhiwang Wei
- grid.412645.00000 0004 1757 9434Department of General Surgery, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052 China
| | - Xiulan Wang
- grid.412645.00000 0004 1757 9434Department of General Surgery, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052 China
| | - Gangjie Qiao
- grid.412645.00000 0004 1757 9434Department of General Surgery, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052 China
| | - Chao Gao
- grid.412645.00000 0004 1757 9434Department of General Surgery, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052 China
| | - Yifan Wang
- grid.412645.00000 0004 1757 9434Department of General Surgery, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052 China
| | - Feng Qi
- grid.412645.00000 0004 1757 9434Department of General Surgery, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052 China
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Livzan MA, Gaus OV, Mozgovoi SI. Gastric cancer in a patient with chronic gastritis after <i>H. pylori</i> eradication: assessing the risks. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2022:22-28. [DOI: 10.31146/1682-8658-ecg-205-9-22-28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]
Abstract
Stomach cancer occupies a leading position in oncological morbidity and mortality worldwide. Approximately 800,000 people die from stomach cancer every year. In two-thirds of patients gastric cancer is diagnosed at a late stage, when radical treatment becomes impossible. Helicobacter pylori (H. pylori) infection is considered as the main etiological factor for gastric cancer. To stratify the risk of developing gastric cancer an assessment of morphological changes in the gastric mucosa using the Operative Link for Gastritis Assessment of Atrophic Gastritis (OLGA) system is used. The stage of gastritis plays a key role in determining an individual’s risk of developing stomach cancer. H. pylori eradication therapy is an effective method for preventing gastric cancer. However not in all patients the elimination of the infection can prevent the development of gastric cancer in the future. It is extremely important to identify a group of people with ex-helicobacter gastritis, who have a high risk of developing stomach cancer, and to take timely preventive measures in them. The purpose of this publication is to summarize and systematize the currently available data on the risk of developing gastric cancer in patients with H. pylori-associated gastritis, including those after successful eradication.
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26
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Guo GH, Xie YB, Zhang PJ, Jiang T. Blood index panel for gastric cancer detection. World J Gastrointest Surg 2022; 14:1026-1036. [PMID: 36185564 PMCID: PMC9521474 DOI: 10.4240/wjgs.v14.i9.1026] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 04/13/2022] [Accepted: 08/18/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Gastric cancer is a common malignant tumor. Early detection and diagnosis are crucial for the prevention and treatment of gastric cancer.
AIM To develop a blood index panel that may improve the diagnostic value for discriminating gastric cancer and gastric polyps.
METHODS Thirteen tumor-related detection indices, 38 clinical biochemical indices and 10 cytokine indices were examined in 139 gastric cancer patients and 40 gastric polyp patients to build the model. An additional 68 gastric cancer patients and 22 gastric polyp patients were enrolled for validation. After area under the curve evaluation and univariate and multivariate analyses.
RESULTS Five tumor-related detection indices, 12 clinical biochemical indices and 1 cytokine index showed significant differences between the gastric cancer and gastric polyp groups. Carbohydrate antigen (CA) 724, phosphorus (P) and ischemia-modified albumin (IMA) were included in the blood index panel, and the area under the curve (AUC) of the index panel was 0.829 (0.754, 0.905). After validation, the AUC was 0.811 (0.700, 0.923). Compared to the conventional index CA724, the blood index panel showed significantly increased diagnostic value.
CONCLUSION We developed an index model that included CA724, P and IMA to discriminate the gastric cancer and gastric polyp groups, which may be a potential diagnostic method for clinical practice.
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Affiliation(s)
- Guang-Hong Guo
- Department of Laboratory Medicine, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Yi-Bin Xie
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Peng-Jun Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Interventional Therapy Department, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Tao Jiang
- Medicine Innovation Research Division of Chinese PLA General Hospital, Beijing 100853, China
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Bi JH, Yuan HY, Jiang Y, Zhang Y, Zheng WW, Zhang L, Li ZY, Li HL, Tan YT, Zhao WS, Xiang YB. Incidence, Mortality Features and Lifetime Risk Estimation of Digestive Tract Cancers in an Urban District of Shanghai, China. J Epidemiol Glob Health 2022; 12:248-257. [PMID: 35751747 PMCID: PMC9470802 DOI: 10.1007/s44197-022-00047-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 06/05/2022] [Indexed: 10/28/2022] Open
Abstract
Digestive tract cancers are the common cause of cancer deaths in both China and worldwide. This study aimed to describe the burden, recent trends and lifetime risks in the incidence and mortality of digestive tract cancers in an urban district of Shanghai, China. Our study extracted data on stomach, colon, rectum and liver cancers diagnosed in Changning District between 2010 and 2019 from the Shanghai Cancer Registry. We calculated age-standardized incidence and mortality rates, the risks of developing and dying from cancer, and the estimated annual percent changes. Between 2010 and 2019, 8619 new cases and 5775 deaths were registered with digestive tract cancers in the district. The age-standardized incidence rates (ASIRs) of liver cancer decreased steadily, whereas the ASIRs of stomach, colon and rectum cancers remained stable from 2010 to 2019. The age-standardized mortality rates (ASMRs) of stomach and liver cancers showed significant declining changes from 2010 to 2019 in both sexes, but that of colon and rectum cancers remained stable during the entire period. The risks of developing and dying from digestive tract cancers were substantially higher in men than women. The burden of digestive tract cancer and its disparities between sex and age group remain major public health challenges in urban Shanghai. To reduce the burden of digestive tract cancers, the government and researchers should develop and promote a healthy diet, organize a screening, and reduce the prevalence of smoking, alcohol drinking, and hepatitis B virus and hepatitis C virus infections.
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Affiliation(s)
- Jing-Hao Bi
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25, Lane 2200, Xie Tu Road, Shanghai, 200032, People's Republic of China
| | - Hui-Yun Yuan
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
- Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25, Lane 2200, Xie Tu Road, Shanghai, 200032, People's Republic of China
| | - Yu Jiang
- Shanghai Changning District Center for Disease Control and Prevention, No. 39, Yun Wu Shan Road, Shanghai, 200051, People's Republic of China
| | - Yun Zhang
- Shanghai Changning District Center for Disease Control and Prevention, No. 39, Yun Wu Shan Road, Shanghai, 200051, People's Republic of China
| | - Wen-Wei Zheng
- Shanghai Changning District Center for Disease Control and Prevention, No. 39, Yun Wu Shan Road, Shanghai, 200051, People's Republic of China
| | - Lei Zhang
- Shanghai Changning District Center for Disease Control and Prevention, No. 39, Yun Wu Shan Road, Shanghai, 200051, People's Republic of China
| | - Zhuo-Ying Li
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25, Lane 2200, Xie Tu Road, Shanghai, 200032, People's Republic of China
| | - Hong-Lan Li
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25, Lane 2200, Xie Tu Road, Shanghai, 200032, People's Republic of China
| | - Yu-Ting Tan
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25, Lane 2200, Xie Tu Road, Shanghai, 200032, People's Republic of China
| | - Wen-Sui Zhao
- Shanghai Changning District Center for Disease Control and Prevention, No. 39, Yun Wu Shan Road, Shanghai, 200051, People's Republic of China.
| | - Yong-Bing Xiang
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
- Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China.
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25, Lane 2200, Xie Tu Road, Shanghai, 200032, People's Republic of China.
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Wang X, Xu K, Liao X, Rao J, Huang K, Gao J, Xu G, Wang D. Construction of a survival nomogram for gastric cancer based on the cancer genome atlas of m6A-related genes. Front Genet 2022; 13:936658. [PMID: 35991573 PMCID: PMC9389082 DOI: 10.3389/fgene.2022.936658] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 07/04/2022] [Indexed: 12/24/2022] Open
Abstract
Objective: Based on TCGA database, a prediction model for 1-, 3-, and 5-year overall survival rates of gastric cancer (GC) patients was constructed by analyzing the critical risk factors affecting the prognosis of gastric cancer patients.Method: Clinicopathological features as well as gene signature of GC patients were obtained from TCGA database. Patients were randomly divided into a training cohort and an internal validation cohort. Independent predictors of GC prognosis were analyzed by univariate and multivariate Cox analyses to construct nomogram. The accuracy and reliability of the model was further validated by calibration curves, ROC curves, and C-indexes, and the clinical utility of the model was analyzed by decision analysis curves.Result: Age, sex, N stage, M stage, METTL16, RBM15, FMR1, IGFBP1, and FTO were significantly associated with the prognosis of GC patients, and these predictors were further included in the construction of nomogram. The C-indexes for the training cohort and validation set were 0.735 and 0.688, respectively. The results of the ROC curve analysis indicated that the area under the curve (AUC) exceeded 0.6 in training and validation sets at 1, 3, and 5 years.Conclusion: We have constructed and validated a nomogram that provides individual survival condition prediction for GC patients. The prognostic model integrating gene signatures and clinicopathological characteristics would help clinicians determine the prognosis of patients with GC and develop individualized treatment plans.
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Affiliation(s)
- Xiaokang Wang
- Department of Pharmacy, Shenzhen Longhua District Central Hospital, Shenzhen, China
- *Correspondence: Xiaokang Wang,
| | - Kexin Xu
- Department of Clinical Medicine, School of the Second Clinical Medicine, Anhui Medical University, Hefei, China
| | - Xueyi Liao
- Shenzhen Key Laboratory of Respiratory Diseases, Shenzhen People’s Hospital (The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Jiaoyu Rao
- Department of Pharmacy, Shenzhen Longhua District Central Hospital, Shenzhen, China
| | - Kaiyuan Huang
- Department of Pharmacy, Shenzhen Longhua District Central Hospital, Shenzhen, China
| | - Jianlin Gao
- Department of Pharmacy, Shenzhen Longhua District Central Hospital, Shenzhen, China
| | - Gengrui Xu
- Department of Pharmacy, Shenzhen Longhua District Central Hospital, Shenzhen, China
| | - Dengchuan Wang
- Department of Pharmacy, Shenzhen Longhua District Central Hospital, Shenzhen, China
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miR-622 Counteracts the NUAK1-Induced Gastric Cancer Cell Proliferation and the Antioxidative Stress. DISEASE MARKERS 2022; 2022:9616764. [PMID: 35872695 PMCID: PMC9303142 DOI: 10.1155/2022/9616764] [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: 04/20/2022] [Revised: 05/25/2022] [Accepted: 06/28/2022] [Indexed: 01/10/2023]
Abstract
Background Gastric cancer (GC), a highly prevalent gastric cancer, has high-risk mortality. Thus, investigating strategies to counteract its growth is important to provide theoretical guidance for its prevention and treatment. It has been pointed out that abnormal expression of microRNAs (miRNAs) serves as noninvasive biomarkers for GC. This present study probed into the role of miR-622 and the NUAK family SNF1-like kinase 1 (NUAK1). Methods Five mRNA datasets (GSE64916, GSE118916, GSE122401, GSE158662, and GSE159721) and one miRNA dataset (GSE128720) from the Gene Expression of Omnibus (GEO) database were used to analyze the differentially expressed miRNAs and mRNA in GC and noncancer samples. Further, western blot, real-time quantitative PCR (qRT-PCR), reactive oxygen species (ROS) assay kit experiments, and wound healing assay, together with in vivo experiments, were performed. Results miR-622 was downregulated, and NUAK1 was upregulated in GC, and NUAK1 was a potential target of miR-622. Knocking down NUAK1 decreased GC cell proliferation and migration but increased oxidative stress in vitro and inhibited the development of tumor in vivo, while miR-622 acted to suppress the action of NUAK1 through the miR-622/NUAK1/p-protein kinase B (Akt) axis, thereby inhibiting the occurrence of GC. Conclusion miR-622 and NUAK1 demonstrated potential for being targets and biomarkers for GC treatment.
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miR-106b as an emerging therapeutic target in cancer. Genes Dis 2022; 9:889-899. [PMID: 35685464 PMCID: PMC9170583 DOI: 10.1016/j.gendis.2021.02.002] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 01/24/2021] [Accepted: 02/03/2021] [Indexed: 12/11/2022] Open
Abstract
MicroRNAs (miRNAs) comprise short non-coding RNAs that function in regulating the expression of tumor suppressors or oncogenes and modulate oncogenic signaling pathways in cancer. miRNAs expression alters significantly in several tumor tissues and cancer cell lines. For example, miR-106b functions as an oncogene and increases in multiple cancers. The miR-106b directly targets genes involved in tumorigenesis, proliferation, invasion, migration, and metastases. This review has focused on the miR-106b function and its downstream target in different cancers and provide perspective into how miR-106 regulates cancer cell proliferation, migration, invasion, and metastases by regulating the tumor suppressor genes. Since miRNAs-based therapies are currently being developed to enhance cancer therapy outcomes, miR-106b could be an attractive and prospective candidate in different cancer types for detection, diagnosis, and prognosis assessment in the tumor.
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31
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Jin G, Zhang J, Cao T, Chen B, Tian Y, Shi Y. Exosome-mediated lncRNA SND1-IT1 from gastric cancer cells enhances malignant transformation of gastric mucosa cells via up-regulating SNAIL1. J Transl Med 2022; 20:284. [PMID: 35739527 PMCID: PMC9229915 DOI: 10.1186/s12967-022-03306-w] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 02/12/2022] [Indexed: 11/20/2022] Open
Abstract
Background Gastric cancer (GC), as one of the most common malignancies across the globe, is the fourth leading cause of cancer-related deaths. Though a large body of research has been conducted to develop the therapeutic methods of GC, the survival rate of advanced patients is still poor. We aimed to dig into the potential regulatory mechanism of GC progression. Methods Bioinformatics tools and fundamental assays were performed at first to confirm the candidate genes in our study. The functional assays and mechanism experiments were conducted to verify the regulatory mechanisms of the genes underlying GC progression. Results Long non-coding RNA (lncRNA) SND1 intronic transcript 1 (SND1-IT1) is highly expressed in exosomes secreted by GC cells. SND1-IT1 was verified to bind to microRNA-1245b-5p (miR-1245b-5p) through competitive adsorption to promote ubiquitin specific protease 3 (USP3) messenger RNA (mRNA) expression. SND1-IT1 was validated to recruit DEAD-box helicase 54 (DDX54) to promote USP3 mRNA stability. SND1-IT1 induces malignant transformation of GES-1 cells through USP3. USP3 mediates the deubiquitination of snail family transcriptional repressor 1 (SNAIL1). Conclusions Exosome-mediated lncRNA SND1-IT1 from GC cells enhances malignant transformation of GES-1 cells via up-regulating SNAIL1. Graphical Abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s12967-022-03306-w.
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Affiliation(s)
- Guohua Jin
- Department of Gastric & Intestine, The First Hospital of Jilin University, No.1 Xinmin Street, Changchun, 130021, Jilin, China
| | - Jianguang Zhang
- Department of Gastric & Intestine, The First Hospital of Jilin University, No.1 Xinmin Street, Changchun, 130021, Jilin, China
| | - Tingting Cao
- Department of Gastric & Intestine, The First Hospital of Jilin University, No.1 Xinmin Street, Changchun, 130021, Jilin, China
| | - Bang Chen
- Department of Gastric & Intestine, The First Hospital of Jilin University, No.1 Xinmin Street, Changchun, 130021, Jilin, China
| | - Yu Tian
- Department of Gastroenterology, The Sixth Affiliated Hospital of Xinjiang Medical University, Urumqi, 830002, Xinjiang, China
| | - Yang Shi
- Department of Gastric & Intestine, The First Hospital of Jilin University, No.1 Xinmin Street, Changchun, 130021, Jilin, China.
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Zhang Y, Gu X, Qin X, Huang Y, Ju S. Evaluation of serum tRF-23-Q99P9P9NDD as a potential biomarker for the clinical diagnosis of gastric cancer. Mol Med 2022; 28:63. [PMID: 35690737 PMCID: PMC9188071 DOI: 10.1186/s10020-022-00491-8] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 05/25/2022] [Indexed: 12/11/2022] Open
Abstract
Background Gastric cancer (GC) is one of the diseases that endanger human health with high morbidity and mortality. The positive rates of traditional biomarkers in the diagnosis of GC are low, so it is necessary to find biomarkers with high sensitivity to increase the detection rate. tRNA-derived small RNAs (tsRNAs) are novel small non-coding RNAs with specific biological functions and aberrant expression in cancer. In this study, we focused on the potential of tRNA-derived small RNAs as GC biomarkers. Methods The differentially expressed tsRNAs in three pairs of GC tissues were screened with high-throughput sequencing and verified using the TCGA database and Quantitative real-time PCR. The methodological evaluation of tRF-23-Q99P9P9NDD was verified by agarose gel electrophoresis, RIN evaluation, and Sanger sequencing. The Chi-square test was used to evaluate the relationship between the tRF-23-Q99P9P9NDD expression and clinicopathological parameters. Kaplan–Meier survival analysis was used to evaluate the effect of the tRF-23-Q99P9P9NDD expression on survival. Additionally, the receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of tRF-23-Q99P9P9NDD in GC. Results Differential expression of serum tRF-23-Q99P9P9NDD could distinguish GC patients from gastritis patients and healthy donors. Chi-square test showed that high expression of tRF-23-Q99P9P9NDD was significantly associated with T stage, lymph node metastasis, TNM stage, and nerve/vascular invasion. Kaplan–Meier curve showed that patients with high expression of tRF-23-Q99P9P9NDD had a lower survival rate than patients with low expression of this biomarker. ROC analysis showed that, compared with conventional biomarkers, the efficacy of tRF-23-Q99P9P9NDD was higher, which was improved by the combination of biomarkers, and even in the early stages. Finally, we preliminarily predicted the downstream of tRF-23-Q99P9P9NDD in GC cells. Conclusions The expression of tRF-23-Q99P9P9NDD in GC serum can identify GC patients, and it has higher efficacy than conventional biomarkers even in the early stages. Furthermore, tRF-23-Q99P9P9NDD can monitor the postoperative conditions of GC patients. Supplementary Information The online version contains supplementary material available at 10.1186/s10020-022-00491-8.
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Affiliation(s)
- Yu Zhang
- Medical School of Nantong University, Nantong University, Nantong, China.,Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Xisi Road, No. 20, Nantong, China.,Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Xinliang Gu
- Medical School of Nantong University, Nantong University, Nantong, China.,Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Xisi Road, No. 20, Nantong, China.,Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Xinyue Qin
- Medical School of Nantong University, Nantong University, Nantong, China.,Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Xisi Road, No. 20, Nantong, China.,Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Yuejiao Huang
- Medical School of Nantong University, Nantong University, Nantong, China. .,Department of Medical Oncology, Affiliated Hospital of Nantong University, Xisi Road, No. 20, Nantong, China.
| | - Shaoqing Ju
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Xisi Road, No. 20, Nantong, China.
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33
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Zheng GL, Zhang GJ, Zhao Y, Zheng ZC. Screening Protein Prognostic Biomarkers for Stomach Adenocarcinoma Based on The Cancer Proteome Atlas. Front Oncol 2022; 12:901182. [PMID: 35574353 PMCID: PMC9096135 DOI: 10.3389/fonc.2022.901182] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 04/06/2022] [Indexed: 12/07/2022] Open
Abstract
The objective was to construct a prognostic risk model of stomach adenocarcinoma (STAD) based on The Cancer Proteome Atlas (TCPA) to search for prognostic biomarkers. Protein data and clinical data on STAD were downloaded from the TCGA database, and differential expressions of proteins between carcinoma and para-carcinoma tissues were screened using the R package. The STAD data were randomly divided into a training set and a testing set in a 1:1 ratio. Subsequently, a linear prognostic risk model of proteins was constructed using Cox regression analysis based on training set data. Based on the scores of the prognostic model, sampled patients were categorized into two groups: a high-risk group and a low-risk group. Using the testing set and the full sample, ROC curves and K-M survival analysis were conducted to measure the predictive power of the prognostic model. The target genes of proteins in the prognostic model were predicted and their biological functions were analyzed. A total of 34 differentially expressed proteins were screened (19 up-regulated, 15 down-regulated). Based on 176 cases in the training set, a prognostic model consisting of three proteins (COLLAGEN VI, CD20, TIGAR) was constructed, with moderate prediction accuracy (AUC=0.719). As shown by the Kaplan-Meier and survival status charts, the overall survival rate of the low-risk group was better than that of the high-risk group. Moreover, a total of 48 target proteins were identified to have predictive power, and the level of proteins in hsa05200 (Pathways in cancer) was the highest. According to the results of the Univariate and multivariate COX analysis, tri-protein was identified as an independent prognostic factor. Therefore, the tri-protein prognostic risk model can be used to predict the likelihood of STAD and guide clinical treatment.
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Affiliation(s)
- Guo-Liang Zheng
- Department of Gastric Surgery, Cancer Hospital of China Medical University (Liaoning Cancer Hospital and Institute), Shenyang, China
| | - Guo-Jun Zhang
- Department of Pathophysiology, College of Basic Medicine Science, China Medical University, Shenyang, China
| | - Yan Zhao
- Department of Gastric Surgery, Cancer Hospital of China Medical University (Liaoning Cancer Hospital and Institute), Shenyang, China
| | - Zhi-Chao Zheng
- Department of Gastric Surgery, Cancer Hospital of China Medical University (Liaoning Cancer Hospital and Institute), Shenyang, China
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Xiong M, Pan B, Wang X, Nie J, Pan Y, Sun H, Xu T, Cho WCS, Wang S, He B. Susceptibility of Genetic Variations in Methylation Pathway to Gastric Cancer. Pharmgenomics Pers Med 2022; 15:441-448. [PMID: 35548064 PMCID: PMC9081620 DOI: 10.2147/pgpm.s340941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 02/17/2022] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND DNA methylation in the CpG island is associated with gastric cancer, genetic variations residue in genes involved in methylation pathway could contribute to the occurrence of gastric cancer. Here, we investigated the association between DNMTs (DNMT1/DNMT3A/DNMT3B), MTHFR genetic variations and gastric cancer risk and patients' survival. PATIENTS AND METHODS We recruited 490 gastric cancer patients and 488 age- and sex-matched healthy controls. The genotypes of the genetic variations were detected by a Mass-array platform. A commercial Helicobacter pylori (H. pylori) immunogold testing kit was used to determine the H. pylori infection. RESULTS We found that carriers of DNMT1 rs2228612C allele was associated with decreased gastric cancer risk (CT vs. TT: adjusted OR = 0.70, 95% CI = 0.53-0.94, P = 0.02; CT/CC vs.TT: adjusted OR = 0.73, 95% CI = 0.56-0.96, P = 0.02). Further stratified analysis showed that DNMT1 rs2228612 CT/CC were associated with a decreased gastric cancer risk in the subgroups of age ≤64 years old (adjusted OR = 0.61, 95% CI = 0.41-0.90, P = 0.01), male (adjusted OR = 0.72, 95% CI = 0.53-0.98, P = 0.03), negative H. pylori infection (adjusted OR = 0.67, 95% CI = 0.45-0.98, P = 0.04), tumor stage T3-T4 (adjusted OR = 0.69, 95% CI = 0.51-0.92, P = 0.01), and non-gastric cardiac adenocarcinoma (NGCA) (adjusted OR = 0.72, 95% CI = 0.54-0.97, P = 0.03). However, none of the genetic variations of this study was associated with overall survival. CONCLUSION We concluded that the DNMT1 rs2228612C genotype is a protective factor for gastric cancer in Han Chinese population.
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Affiliation(s)
- Mengqiu Xiong
- Clinical Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, People’s Republic of China
| | - Bei Pan
- Medical College, Southeast University, Nanjing, 210006, People’s Republic of China
| | - Xuhong Wang
- Medical College, Southeast University, Nanjing, 210006, People’s Republic of China
| | - Junjie Nie
- Clinical Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, People’s Republic of China
| | - Yuqin Pan
- Clinical Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, People’s Republic of China
| | - Huiling Sun
- Clinical Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, People’s Republic of China
| | - Tao Xu
- Clinical Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, People’s Republic of China
| | - William C S Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Hongkong SAR, People’s Republic of China
| | - Shukui Wang
- Clinical Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, People’s Republic of China
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, People’s Republic of China
- Helicobacter pylori Research Key Laboratory, Nanjing Medical University, Nanjing, 211166, People’s Republic of China
| | - Bangshun He
- Clinical Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, People’s Republic of China
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, People’s Republic of China
- Helicobacter pylori Research Key Laboratory, Nanjing Medical University, Nanjing, 211166, People’s Republic of China
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Zhuang SH, Meng CC, Fu JJ, Huang J. Long non-coding RNA ELFN1-AS1-mediated ZBTB16 inhibition augments the progression of gastric cancer by activating the PI3K/AKT axis. Kaohsiung J Med Sci 2022; 38:621-632. [PMID: 35451560 DOI: 10.1002/kjm2.12548] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 02/07/2022] [Accepted: 03/07/2022] [Indexed: 12/24/2022] Open
Abstract
Long non-coding RNA ELFN1 antisense RNA 1 (ELFN1-AS1) has been reported as a cancer driver in many human malignancies. This study was conducted to investigate the function of ELFN1-AS1 in gastric cancer (GC) and its mechanism of action. Bioinformatics analysis revealed increased expression of ELFN1-AS1 in GC, and abundant expression of ELFN1-AS1 was observed in the acquired GC cell lines. Knockdown of ELFN1-AS1 in GC cells weakened cell proliferation, invasion, migration, and resistance to apoptosis. ELFN1-AS1 was mainly localized in the nuclei of GC cells. ELFN1-AS1 recruited DNA methyltransferases to the promoter region of ZBTB16 and induced transcriptional repression of ZBTB16 through methylation modification. Furthermore, downregulation of ZBTB16 activated the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and restored the proliferation and invasiveness of GC cells. In vivo, downregulation of ELFN1-AS1 reduced the growth rate of xenograft tumors in mice. In summary, this study demonstrates that ELFN1-AS1 recruits DNA methyltransferases to the promoter region of ZBTB16 to induce its transcriptional repression, which further augments the development of GC by activating the PI3K/AKT signaling pathway.
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Affiliation(s)
- Shao-Hua Zhuang
- Department of Gastroenterology, Changzhou No.2 People's Hospital Affiliated to Nanjing Medical University, Changzhou, China
| | - Chu-Chen Meng
- Department of Endocrinology, Changzhou No.2 People's Hospital Affiliated to Nanjing Medical University, Changzhou, China
| | - Jin-Jin Fu
- Department of Gastroenterology, Changzhou No.2 People's Hospital Affiliated to Nanjing Medical University, Changzhou, China
| | - Jian Huang
- Department of Gastroenterology, Changzhou No.2 People's Hospital Affiliated to Nanjing Medical University, Changzhou, China
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Song J, Fu Q, Liu G, Zhang C, Wang Y, Tao S, Liu R, Li Z. TULP3 silencing suppresses cell proliferation, migration and invasion in gastric cancer via the PTEN/Akt/Snail pathway. Cancer Treat Res Commun 2022; 31:100551. [PMID: 35344762 DOI: 10.1016/j.ctarc.2022.100551] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 03/11/2022] [Accepted: 03/20/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND Tubby-like protein 3 (TULP3) is a member of the tubby family, has been related to the development of nervous system by gene knockout researches. Nevertheless, the role of TULP3 in the gastric cancer is not clear. METHODS Western blotting and real-time polymerase chain reaction (PCR) were employed for the quantitative detection of TULP3 expression in the gastric cancer and consecutive non-cancerous tissues, and gastric cancer cells. The roles of TULP3 in invasion, migration as well as proliferation of the gastric cancer cell in vivo and in vitro through utilizing colony formation, MTT, wound-healing, transwell and mouse xenograft model. Western blotting assay was implemented in order to clarify the potential molecular mechanisms. Furthermore, electron microscopy and western blot were evaluated TULP3 expression in gastric cancer patient extracted serum exosomes. RESULTS TULP3 expression levels were remarkably upregulated in the gastric cancer tissues and cells. Subsequent functional assays demonstrated that TULP3 downregulation suppressed invasion, migration as well as the proliferation of the gastric cancer cell. Mechanism assays depicted that the PTEN/Akt/Snail signaling pathway can inhibit invasion, migration as well as the proliferation of the gastric cancer cell via TULP3 silencing. Finally, we found that the expression of TULP3 could be determined in the extracted serum exosomes. The expression of TULP3 in gastric cancer group was higher in comparison with normal group. CONCLUSIONS Our results reveal that TULP3 might serve as a potential prognostic biomarker and therapeutic target for the treatment of gastric cancer.
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Affiliation(s)
- Jun Song
- Department of Laboratory Medicine, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province 241001, China
| | - Qingsheng Fu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province 241001, China
| | - Gang Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province 241001, China
| | - Chengxiong Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province 241001, China
| | - Yingying Wang
- Department of Nuclear medicine, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province 241001, China
| | - Shaoneng Tao
- Department of Nuclear medicine, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province 241001, China.
| | - Rui Liu
- Department of Laboratory Medicine, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province 241001, China.
| | - Zhi Li
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province 241001, China.
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37
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The immunological role of CD4 and CD8 in patients infected with Helicobacter pylori and stomach cancer. GENE REPORTS 2022. [DOI: 10.1016/j.genrep.2022.101500] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Li Q, Zhou ZW, Lu J, Luo H, Wang SN, Peng Y, Deng MS, Song GB, Wang JM, Wei X, Wang D, Westover KD, Xu CX. PD-L1 P146R is prognostic and a negative predictor of response to immunotherapy in gastric cancer. Mol Ther 2022; 30:621-631. [PMID: 34547468 PMCID: PMC8821936 DOI: 10.1016/j.ymthe.2021.09.013] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 09/07/2021] [Accepted: 09/14/2021] [Indexed: 02/04/2023] Open
Abstract
Cancer cells evade immune detection via programmed cell death 1/programmed cell death-ligand 1 (PD-1/PD-L1) interactions that inactivate T cells. PD-1/PD-L1 blockade has become an important therapy in the anti-cancer armamentarium. However, some patients do not benefit from PD-1/PD-L1 blockade despite expressing PD-L1. Here, we screened 101 gastric cancer (GC) patients at diagnosis and 141 healthy control subjects and reported one such subpopulation of GC patients with rs17718883 polymorphism in PD-L1, resulting in a nonsense P146R mutation. We detected rs17718883 in 44% of healthy control subjects, and rs17718883 was associated with a low susceptibility to GC and better prognosis in GC patients. Structural analysis suggests that the mutation weakens the PD-1:PD-L1 interaction. This was supported by co-culture experiments of T cells, with GC cells showing that the P146R substitution results in interferon (IFN)-γ secretion by T cells and enables T cells to suppress GC cell growth. Similar results with animal gastric tumor models were obtained in vivo. PD-1 monoclonal antibody treatment did not enhance the inhibitory effect of T cells on GC cells expressing PD-L1P146Rin vitro or in vivo. This study suggests that rs17718883 is common and may be used as a biomarker for exclusion from PD-1/PD-L1 blockade therapy.
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Affiliation(s)
- Qing Li
- Cancer Center, Daping Hospital, Army Medical University, Chongqing 400042, China,School of Medicine, Chongqing University, Chongqing 400030, China
| | - Zhi-Wei Zhou
- Department of Radiation Oncology and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Jia Lu
- Department of Radiation Oncology and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Hao Luo
- Cancer Center, Daping Hospital, Army Medical University, Chongqing 400042, China,Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China
| | - Shu-Nan Wang
- Department of Radiology, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Yu Peng
- Shanghai Key Laboratory of Regulatory Biology, The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China
| | - Meng-Sheng Deng
- State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Guan-Bin Song
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China
| | - Jian-Min Wang
- State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Xi Wei
- Department of Diagnostic Ultrasound, Tianjin Medical University Cancer Institute and Hospital, Tianjin 330006, China
| | - Dong Wang
- Cancer Center, Daping Hospital, Army Medical University, Chongqing 400042, China,Corresponding author: Dong Wang, Cancer Center, Daping Hospital, Army Medical University, Chongqing 400042, China.
| | - Kenneth D. Westover
- Department of Radiation Oncology and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA,Corresponding author: Kenneth D. Westover, Department of Radiation Oncology and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
| | - Cheng-Xiong Xu
- Cancer Center, Daping Hospital, Army Medical University, Chongqing 400042, China,School of Medicine, Chongqing University, Chongqing 400030, China,Corresponding author: Cheng-Xiong Xu, School of Medicine, Chongqing University, Chongqing 400030, China.
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Pang J, Li G, Qian H, Wu Y, Chen Y. Secretory PKG II blocks activation of PDGFRβ via Ser254 in gastric cancer cells. Cell Biol Int 2022; 46:747-754. [PMID: 35066967 PMCID: PMC9305209 DOI: 10.1002/cbin.11766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 12/28/2021] [Accepted: 01/08/2022] [Indexed: 11/06/2022]
Affiliation(s)
- Ji Pang
- Department of Physiology, School of Medicine, Jiangsu UniversityZhenjiang CityJiangsu Province212013People's Republic of China
| | - Guorui Li
- Department of Physiology, School of Medicine, Jiangsu UniversityZhenjiang CityJiangsu Province212013People's Republic of China
| | - Hai Qian
- Department of Physiology, School of Medicine, Jiangsu UniversityZhenjiang CityJiangsu Province212013People's Republic of China
| | - Yan Wu
- Department of Physiology, School of Medicine, Jiangsu UniversityZhenjiang CityJiangsu Province212013People's Republic of China
| | - Yongchang Chen
- Department of Physiology, School of Medicine, Jiangsu UniversityZhenjiang CityJiangsu Province212013People's Republic of China
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40
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Melim C, Lauro MR, Pires IM, Oliveira PJ, Cabral C. The Role of Glucosinolates from Cruciferous Vegetables (Brassicaceae) in Gastrointestinal Cancers: From Prevention to Therapeutics. Pharmaceutics 2022; 14:pharmaceutics14010190. [PMID: 35057085 PMCID: PMC8777706 DOI: 10.3390/pharmaceutics14010190] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 12/31/2021] [Accepted: 01/10/2022] [Indexed: 02/04/2023] Open
Abstract
The gastrointestinal (GI) tract is composed of rapidly renewing cells, which increase the likelihood of cancer. Colorectal cancer is one of the most frequently diagnosed GI cancers and currently stands in second place regarding cancer-related mortality. Unfortunately, the treatment of GI is limited, and few developments have occurred in the field over the years. With this in mind, new therapeutic strategies involving biologically active phytocompounds are being evaluated as anti-cancer agents. Vegetables such as broccoli, brussels sprouts, cabbage, cauliflower, and radish, all belonging to the Brassicaceae family, are high in dietary fibre, minerals, vitamins, carotenoids, polyphenols, and glucosinolates. The latter compound is a secondary metabolite characteristic of this family and, when biologically active, has demonstrated anti-cancer properties. This article reviews the literature regarding the potential of Cruciferous vegetables in the prevention and/or treatment of GI cancers and the relevance of appropriate compound formulations for improving the stability and bioaccessibility of the major Cruciferous compounds, with a particular focus on glucosinolates.
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Affiliation(s)
- Catarina Melim
- Faculty of Medicine, Clinic Academic Center of Coimbra (CACC), Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3000-548 Coimbra, Portugal;
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal;
| | - Maria R. Lauro
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 84084 Fisciano, Italy;
| | - Isabel M. Pires
- Department of Biomedical Sciences, Faculty of Health Sciences, University of Hull, Hull HU6 7RX, UK;
| | - Paulo J. Oliveira
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal;
- CNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal
| | - Célia Cabral
- Faculty of Medicine, Clinic Academic Center of Coimbra (CACC), Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3000-548 Coimbra, Portugal;
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal;
- Center for Functional Ecology, Department of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal
- Correspondence: ; Tel.: +351-239-480-066
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41
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Cheng Z, Hong J, Tang N, Liu F, Gu S, Feng Z. Long non-coding RNA p53 upregulated regulator of p53 levels (PURPL) promotes the development of gastric cancer. Bioengineered 2022; 13:1359-1376. [PMID: 35012438 PMCID: PMC8805877 DOI: 10.1080/21655979.2021.2017588] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Gastric cancer (GC), one of the most prevalent malignancies across the world, has an increasing incidence rate. Long non-coding RNA (lncRNA) PURPL (also referred to as LINC01021) has been demonstrated to influence malignant GC behaviors and partake in other cancers. Notwithstanding, reports pertaining to the underlying mechanism of PURPL in GC haven’t been rarely seen. Presently, in-vivo and ex-vivo experiments were implemented to examine the PURPL-miR-137-ZBTB7A-PI3K-AKT-NF-κB regulatory axis in GC. Our statistics revealed that PURPL presented a high expression in GC tissues and cell lines. PURPL overexpression remarkably exacerbated colony formation, migration, and invasion and repressed apoptosis in GC cells (AGS and MNK-45). In-vivo experiments also corroborated that cell growth was boosted by PURPL up-regulation. Mechanistic investigations verified that PURPL interacted with miR-137 and lowered its profile in GC cell lines. miR-137 overexpression or ZBTB7A knockdown upended the oncogenic function mediated by PURPL. PURPL initiated the PI3K/AKT/NF-κB pathway. PI3K and NF-κB inhibition impaired the promoting impact on GC cells elicited by PURPL overexpression and contributed to PURPL down-regulation. These findings disclosed that PURPL serves as an oncogene in the context of GC via miR-137-ZBTB7A-PI3K-AKT-NF-κB axis modulation.
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Affiliation(s)
- Zhonghua Cheng
- Department of Gastroenterology, The Central Hospital of Xuhui District, Xuhui Hospital, Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
| | - Jing Hong
- Department of Gastroenterology, The Central Hospital of Xuhui District, Xuhui Hospital, Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
| | - Nan Tang
- Department of Gastroenterology, The Central Hospital of Xuhui District, Xuhui Hospital, Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
| | - Fenghua Liu
- Department of Gastroenterology, The Central Hospital of Xuhui District, Xuhui Hospital, Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
| | - Shuo Gu
- Department of Gastroenterology, The Central Hospital of Xuhui District, Xuhui Hospital, Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
| | - Zhen Feng
- Department of Gastroenterology, The Central Hospital of Xuhui District, Xuhui Hospital, Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
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Zhu J, Du S, Zhang J, Huang G, Dong L, Ren E, Liu D. microRNA-10a-5p from gastric cancer cell-derived exosomes enhances viability and migration of human umbilical vein endothelial cells by targeting zinc finger MYND-type containing 11. Bioengineered 2022; 13:496-507. [PMID: 34969361 PMCID: PMC8805907 DOI: 10.1080/21655979.2021.2009962] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 11/18/2021] [Indexed: 12/20/2022] Open
Abstract
Tumor-derived exosomes (exo) could modulate the biological behaviors of human umbilical vein endothelial cells (HUVECs). Here, the role of microRNA (miR)-10a-5p-modified gastric cancer (GC) cells-derived exo for HUVECs was studied. GC tissue specimens were collected, and miR-10a-5p and zinc finger MYND-type containing 11 (ZMYND11) levels were determined. HUVECs interfered with ZMYND11 or miR-10a-5p-related oligonucleotides. Exo was extracted from GC cells (HGC-27 exo), and miR-10a-5p mimic-modified HGC-27 exo were co-cultured with HUVECs. HUVECs viability, migration and angiogenesis were evaluated, and miR-10a-5p/ZMYND11 crosstalk was explored. It was observed that GC patients had raised miR-10a-5p and reduced ZMYND11, and miR-10a-5p negatively mediated ZMYND11 expression. Suppression of miR-10a-5p or overexpression of ZMYND11 inhibited viability, migration and tube formation ability of HUVECs. Notably, miR-10a-5p mimic-modified HGC-27 exo enhanced the viability, migration and tube formation ability of HUVECs, but this effect was impaired after up-regulating ZMYND11. In summary, miR-10a-5p from GC cells-derived exo enhances viability and migration of HUVECs by suppressing ZMYND11.
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Affiliation(s)
- Jiaxin Zhu
- Department of Gastrointestinal Surgery, the First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, China
| | - Shasha Du
- Department of Nephrology, the First Affiliated Hospital, And College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, China
| | - Jianfeng Zhang
- Department of Gastrointestinal Surgery, the First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, China
| | - Guangzhao Huang
- Department of Emergency Medicine, the First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, China
| | - Lujia Dong
- Department of Gastrointestinal Surgery, the First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, China
| | - Enbo Ren
- Department of Gastrointestinal Surgery, the First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, China
| | - Dechun Liu
- Department of Gastrointestinal Surgery, the First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, China
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43
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Maharjan U, Kauppila JH. Survival trends in gastric cancer patients between 1987 and 2016: a population-based cohort study in Finland. Gastric Cancer 2022; 25:989-1001. [PMID: 35933683 PMCID: PMC9587955 DOI: 10.1007/s10120-022-01326-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 07/18/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND Gastric cancer is the fourth leading cause of cancer-related deaths globally. There is a paucity of national studies examining gastric cancer mortality in relation to treatment status. This study evaluated the survival trends in gastric adenocarcinoma and all gastric cancers stratified by treatment in Finland during 1987-2016. METHODS This population-based, nationwide, retrospective cohort study included all gastric cancer patients registered in the Finnish Cancer Registry and Patient Registry. The survival rates were calculated for 1, 3, and 5 years, stratified by treatment. Prognostic factors were determined using Cox regression. RESULTS A total of 18,713 non-cardia gastric adenocarcinoma, and 3617 cardia adenocarcinoma patients were included. Surgical treatment decreased for non-cardia adenocarcinoma and remained constant for cardia adenocarcinoma. In non-cardia adenocarcinoma, the 5-year survival declined from 17% to 16% from 1987-1991 to 2012-2016. In surgically treated patients, survival increased from 29% to 38%, while an increase from 4% to 7% in those undergoing chemotherapy and decrease from 6% to 3% in those not receiving any treatment were observed. In cardia adenocarcinoma, the 5-year survival increased from 10% to 18% in all patients, 16% to 40% in surgical patients, 0% to 5% in patients receiving chemotherapy, and from 5% to 9% in patients receiving no treatment. Earlier calendar periods, older age, male sex, and higher comorbidity were risk factors for poor prognosis. CONCLUSIONS Gastric non-cardia adenocarcinoma survival declined, limited to advanced stage patients not receiving any treatment. Gastric cardia cancer survival seems to have improved over time in Finland. This study evaluated survival trends of gastric cancer in Finland during 1987-2016 and established that the 5-year survival is declining in non-cardia adenocarcinoma but improving in all gastric cancers.
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Affiliation(s)
- Urgena Maharjan
- Present Address: Surgery Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
| | - Joonas H. Kauppila
- Present Address: Surgery Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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44
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Tuo JY, Bi JH, Yuan HY, Jiang YF, Ji XW, Li HL, Xiang YB. Trends of stomach cancer survival: A systematic review of survival rates from population-based cancer registration. J Dig Dis 2022; 23:22-32. [PMID: 34821032 DOI: 10.1111/1751-2980.13070] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 09/14/2021] [Accepted: 11/22/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVES We aimed to describe the pattern and time trends of survival from stomach cancer worldwide from population-based cancer registers. METHODS A systematic search of PubMed, Web of Science, EMBASE, SEER and SinoMed for articles published up to 31 December 2020 was conducted. All eligible survival analyses of stomach cancer were collected and evaluated by countries or regions, periods, sex and age groups. RESULTS Our review included 76 articles on stomach cancer survival rates and found that these rates had improved globally with time, although this increase was unremarkable. The highest 5-year survival rate of 72.1% was observed in Japan (2004-2007). The 5-year relative and net survival, rates were relatively high in Korea and Japan, while they were fairly poor in Africa and India. Sex-specific survival rates were higher in women than in men in America, Europe and Oceania, whereas they were relatively low in Asia. The poorest age-specific 5-year relative and net survival rates were observed in patients aged over 75 years. CONCLUSIONS Over the past decades, patient prognosis of stomach cancer has gradually improved worldwide and survival rates in developed regions were higher than those in developing regions. White men and Asian women had a poorer survival than white women and Asian men. Younger patients had better survival rates than those aged over 75 years globally.
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Affiliation(s)
- Jia Yi Tuo
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jing Hao Bi
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Hui Yun Yuan
- Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yu Fei Jiang
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.,Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Xiao Wei Ji
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Hong Lan Li
- State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yong Bing Xiang
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.,Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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45
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Zhang HH, Soyfoo MD, Cao JL, Sang HM, Xu SF, Jiang JX. Histopathological Characteristics and Therapeutic Outcomes of Endoscopic Submucosal Dissection for Gastric High-Grade Intraepithelial Neoplasia. J Laparoendosc Adv Surg Tech A 2021; 32:413-421. [PMID: 34962142 DOI: 10.1089/lap.2020.0035] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Affiliation(s)
- Hai-Han Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Muhammad Djaleel Soyfoo
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jiu-Liang Cao
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Huai-Ming Sang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Shun-Fu Xu
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jian-Xia Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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46
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Zhao Y, Li Y, Luan Z, Ma C, Yang L, Zhang W, Shi C. Establishment of a TaqMan-MGB probe multiplex real-time PCR system for one-step levofloxacin and clarithromycin resistant Helicobacter pylori detection. J Microbiol Methods 2021; 192:106393. [PMID: 34919971 DOI: 10.1016/j.mimet.2021.106393] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 12/10/2021] [Accepted: 12/10/2021] [Indexed: 12/16/2022]
Abstract
Due to the abuse of antibiotics, the prevalence of antibiotic resistant Helicobacter pylori strains continues to increase. Therefore, antibiotic resistance assessment is now essential in addition to general H. pylori diagnosis in medical institutions to fulfill clinicians administering effective antibiotic regimens. However, the conventional antibiotic resistance assessment methods, such as in vitro antibiotic susceptibility test and E-test, are skilled-staff dependent and time-consuming. The aim of this study was to establish an easy-operating TaqMan-MGB probe multiplex real-time PCR system for one-step detection of levofloxacin and clarithromycin resistance mutations with concurrent H. pylori infection diagnosis. Through the optimization of primers, probes and reaction buffers, this proposed system could accurately distinguish the recombinant plasmids with different mutation markers. More importantly, the diagnosis results of this detection system exhibited excellent consistence with the gold standard of gastric biopsy and Sanger sequencing on the detection of H. pylori infection and relevant antibiotic resistant strains, the Kappa values of which all exceeded 0.90. In addition, the results of this detection system could also be applied for the prevalence statistics of antibiotic resistance patterns for patients by age, gender and geographical location. This simple and rapid system should be beneficial for clinicians issuing personalized treatments according to the patient's H. pylori strains and avoid the abuse of antibiotics.
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Affiliation(s)
- Yan Zhao
- Qingdao Nucleic Acid Rapid Testing International Science and Technology Cooperation Base, College of Life Sciences, Department of Pathogenic Biology, School of Basic Medicine, and Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, PR China
| | - Yang Li
- Qingdao Nucleic Acid Rapid Testing International Science and Technology Cooperation Base, College of Life Sciences, Department of Pathogenic Biology, School of Basic Medicine, and Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, PR China
| | - Zhixian Luan
- Qingdao Nucleic Acid Rapid Testing International Science and Technology Cooperation Base, College of Life Sciences, Department of Pathogenic Biology, School of Basic Medicine, and Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, PR China
| | - Cuiping Ma
- Shandong Provincial Key Laboratory of Biochemical Engineering, Qingdao Nucleic Acid Rapid Detection Engineering Research Center, College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao 266042, PR China
| | - Lin Yang
- Department of Gastroenterology, the Affiliated Hospital of Qingdao University, Qingdao, China
| | - Wang Zhang
- Department of Gastroenterology, the Affiliated Hospital of Qingdao University, Qingdao, China
| | - Chao Shi
- Qingdao Nucleic Acid Rapid Testing International Science and Technology Cooperation Base, College of Life Sciences, Department of Pathogenic Biology, School of Basic Medicine, and Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, PR China.
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Deng T, Jiang X, He Z, Cai M, Chen C, Xu Z. Centromere protein U (CENPU) promotes gastric cancer cell proliferation and glycolysis by regulating high mobility group box 2 (HMGB2). Bioengineered 2021; 12:10194-10202. [PMID: 34872447 PMCID: PMC8810026 DOI: 10.1080/21655979.2021.2002018] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Gastric cancer is one of the most common malignancy with a leading mortality rate worldwide. Despite the progress in the diagnosis and therapeutic strategy, the associated mortality is still growing. It is of great significance to understand molecular mechanisms of the development of gastric cancer. Glycolysis is a main source of ATP provision for cancer cells including gastric cancer, and targeting glycolysis is a promising therapeutic strategy. Centromere protein U (CENPU) has been found to be overexpressed in many types of cancer. Downregulation of CENPU suppresses the proliferation and invasion of cancer cells. High mobility group box 2 (HMGB2) is identified as a biomarker to diagnose of gastric cancer. Knockdown of HMGB2 inhibits proliferation and glycolysis in gastric cancer cells. In this work, we identified that CENPU was upregulated in gastric cancer. Knockdown of CENPU was able to suppress the proliferation and glycolysis of gastric cancer cells. Further the results showed that the anti-cancer effect of CENPU was HMGB2-dependent. Taken together, CENPU is an upstream factor of HMGB2, which regulates proliferation and glycolysis of gastric cancer.
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Affiliation(s)
- Taozhi Deng
- Department of Gastroenterology, Hainan Cancer Hospital, Haikou, Hainan Province, China
| | - Xuemei Jiang
- Department of Gastroenterology, Hainan General Hospital, Haikou, Hainan Province, China
| | - Zhoutao He
- Department of Gastroenterology, Hainan General Hospital, Haikou, Hainan Province, China
| | - Manni Cai
- Department of Gastroenterology, Hainan General Hospital, Haikou, Hainan Province, China
| | - Chaochao Chen
- Department of Gastroenterology, Hainan General Hospital, Haikou, Hainan Province, China
| | - Zewen Xu
- Department of Gastroenterology, Hainan General Hospital, Haikou, Hainan Province, China
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48
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Wang Y, Liu X, Wang L, Zhang Z, Li Z, Li M. Circ_PGPEP1 Serves as a Sponge of miR-1297 to Promote Gastric Cancer Progression via Regulating E2F3. Dig Dis Sci 2021; 66:4302-4313. [PMID: 33386518 DOI: 10.1007/s10620-020-06783-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 12/11/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND Circular RNA (circRNA) is a special kind of noncoding RNA that plays a vital function in the progression of gastric cancer (GC). However, the role of a new circRNA, circ_PGPEP1, in GC is unclear. AIMS Exploring the role and mechanism of circ_PGPEP1 in GC progression. METHODS The expression levels of circ_PGPEP1, miR-1297, and E2F transcription factor 3 (E2F3) were determined using quantitative real-time PCR. Flow cytometry, colony formation assay, MTT assay, and transwell assay were used to evaluate cell cycle, apoptosis, proliferation, migration, and invasion. The protein levels of apoptosis-related markers and E2F3 were measured by western blot analysis. The interaction between circ_PGPEP1 and miR-1297 or miR-1297 and E2F3 was confirmed by dual-luciferase reporter assay. In addition, animal experiments were performed to assess the effect of circ_PGPEP1 on GC tumor growth in vivo. RESULTS Circ_PGPEP1 was a highly expressed circRNA in GC. Loss-of-function experiment indicated that circ_PGPEP1 silencing could induce cell cycle arrest and apoptosis, while inhibit proliferation, migration, and invasion in GC cells. MiR-1297 could be sponged by circ_PGPEP1, and its expression was downregulated in GC. MiR-1297 inhibitor could reverse the negatively regulation of circ_PGPEP1 knockdown on GC progression. Furthermore, we also found that E2F3 could be targeted by miR-1297, and its expression was positively regulated by circ_PGPEP1. Overexpression of E2F3 could invert the inhibitory effect of miR-1297 on GC progression. Animal experiments suggested that silenced circ_PGPEP1 could reduce GC tumor growth. CONCLUSION Our research showed that circ_PGPEP1 might serve as a potential biomarker for GC.
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Affiliation(s)
- Yingxin Wang
- Department of General Surgery, Shijiazhuang People's Hospital, No. 365 Jianhuanan Street, Shijiazhuang, 050031, Hebei, China
| | - Xia Liu
- Department of Forensic Pathology, Hebei Medical University, Shijiazhuang, 050017, Hebei, China
| | - Liwei Wang
- Department of General Surgery, Shijiazhuang People's Hospital, No. 365 Jianhuanan Street, Shijiazhuang, 050031, Hebei, China
| | - Zhenduo Zhang
- Department of General Surgery, Shijiazhuang People's Hospital, No. 365 Jianhuanan Street, Shijiazhuang, 050031, Hebei, China
| | - Zhong Li
- Department of General Surgery, Shijiazhuang People's Hospital, No. 365 Jianhuanan Street, Shijiazhuang, 050031, Hebei, China
| | - Ming Li
- Department of General Surgery, Shijiazhuang People's Hospital, No. 365 Jianhuanan Street, Shijiazhuang, 050031, Hebei, China.
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Han X, Wang DZ, Yuan M, Bai WJ. Lemur tyrosine kinase 2 silencing inhibits the proliferation of gastric cancer cells by regulating GSK-3β phosphorylation and β-catenin nuclear translocation. Bioengineered 2021; 13:6231-6243. [PMID: 34719320 PMCID: PMC8982461 DOI: 10.1080/21655979.2021.1999375] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Previous studies on the mechanism of proliferation and cell cycle progression of gastric cancer cells have shown promising perspectives for the prevention and treatment of gastric cancer. The aim of the present study was to investigate the role of lemur tyrosine kinase 2 (LMTK2) in gastric cancer cell proliferation and cell cycle progression, as well as in tumor-bearing nude mouse models. The expression levels of LMTK2 were determined in gastric cancer cell lines. In addition, the effects of LMTK2 silencing or overexpression on cell proliferation were measured using Cell Counting Kit-8, BrdU and colony formation assays. Cell cycle progression was analyzed using flow cytometry and western blotting. The expression levels of proteins associated with the β-catenin pathway were assessed using western blot analysis. A tumor-bearing nude mouse model was established by injecting gastric cancer cells, and the effect of LMTK2 knockdown or overexpression on tumor growth was examined. The expression levels of LMTK2 were found to be upregulated in all gastric cancer cell lines. Moreover, LMTK2 knockdown inhibited cell proliferation, colony formation and cell cycle progression. LMTK2 knockdown also inhibited the activation of GSK-3β/β-catenin signaling, as evidenced by reduced GSK-3β phosphorylation and nuclear β-catenin levels. LMTK2 knockdown also suppressed tumor growth, whereas overexpression accelerated this process. In conclusion, LMTK2 silencing can inhibit the proliferation of gastric cancer cells in vitro and tumor growth in vivo by regulating GSK-3β phosphorylation and β-catenin nuclear translocation.
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Affiliation(s)
- Xin Han
- Department of Thoracic Cancer, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China
| | - Da-Zhong Wang
- Department of Thoracic Cancer, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China
| | - Meng Yuan
- Department of Thoracic Cancer, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China
| | - Wei-Jun Bai
- Department of Thoracic Cancer, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China
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SLCO4A1-AS1 Facilitates the Malignant Phenotype via miR-149-5p/STAT3 Axis in Gastric Cancer Cells. JOURNAL OF ONCOLOGY 2021; 2021:1698771. [PMID: 34712324 PMCID: PMC8548156 DOI: 10.1155/2021/1698771] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 07/13/2021] [Accepted: 08/10/2021] [Indexed: 12/29/2022]
Abstract
Solute carrier organic anion transporter family member 4A1 (SLCO4A1-AS1), a newly discovered lncRNA, may exert effects in tumors. Since its role in gastric cancer remains obscure, we sought to explore the mechanism of SLCO4A1-AS1 in gastric cancer. The relationship among SLCO4A1-AS1, miR-149-5p, and STAT3 was detected by bioinformatics, dual luciferase analysis, and Pearson's test, and the expressions of these genes were determined by quantitative real-time PCR and Western blot. Moreover, CCK-8, flow cytometry, wound healing assay, and Transwell analysis were performed to verify the function of SLCO4A1-AS1 in gastric cancer. Rescue experiments were used to detect the role of miR-149-5p. The expressions of SLCO4A1-AS1 and STAT3 were increased, while the expression of miR-149-5p was suppressed in gastric cancer tissues and cell lines. In addition, STAT3 expression was negatively correlated with miR-149-5p expression but was positively correlated with SLCO4A1-AS1 expression. Overexpression of SLCO4A1-AS1 promoted cell viability, migration, invasion, and STAT3 expression but suppressed apoptosis, while knockdown of SLCO4A1-AS1 had the opposite effect. SLCO4A1-AS1 bound to miR-149-5p and targeted STAT3. Moreover, miR-149-5p mimic inhibited the malignant development of gastric cancer cells and obviously reversed the function of SLCO4A1-AS1 overexpression. Our research reveals that abnormally increased SLCO4A1-AS1 expression may be an important molecular mechanism in the development of gastric cancer.
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