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Song L, Wang G, Chen Z, Wang G. Research status of risk factors and prevention of pancreatic cancer: A bibliometric and visual analysis. Medicine (Baltimore) 2025; 104:e41831. [PMID: 40101086 PMCID: PMC11922469 DOI: 10.1097/md.0000000000041831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/20/2025] Open
Abstract
One of the biggest public health issues facing the globe today is pancreatic cancer (PC). To serve as a guide for clinically identifying existing research hotspots and conducting related studies in the future, bibliometric and visualization analyses of the literature on risk factors and PC prevention were carried out in this work. Results of published research from 2004 to 2024 were retrieved using the Web of Science database as a search platform. CiteSpace and VOSviewer were used for bibliometric and visual analysis. Based on the exclusion criteria, 868 articles in all were screened. Between 2004 and 2024, the quantity of articles published varied. Between 2017 and 2023, there was a consistent upward trend in the quantity of published literature. Cancer epidemiology biomarkers and prevention, cancers, and the Asian Pacific Journal of Cancer Prevention were the 3 journals with the most publications. The 2 nations with the most publications are China and the United States. The 2 nations with the most publications are China and the United States. The top 3 most published universities are Harvard University, the National Institutes of Health (NIH), and the National Cancer Institute (NCI). Buzzwords include body mass index, obesity, diabetes, smoking, and exercise.
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Affiliation(s)
- Lichen Song
- School of Clinical Medicine, Dali University, Dali, China
| | - Guihua Wang
- Respiratory and Critical Care Medicine Department, The First Affiliated Hospital of Dali University, Dali, China
| | - Ziyi Chen
- School of Clinical Medicine, Dali University, Dali, China
| | - Guangming Wang
- Center of Genetic Testing, The First Affiliated Hospital of Dali University, Dali, China
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Ouyang Y, Zhou B, Chu L, Chen X, Hao Q, Lei J. Causal associations of tea consumption on risk of pancreatic adenocarcinoma and the mediating role of vascular endothelial growth factor D levels. Br J Nutr 2024; 132:1503-1512. [PMID: 39501829 DOI: 10.1017/s0007114524002393] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2024]
Abstract
Tea is one of the most widely consumed beverages in the world. However, the association between tea and risk of pancreatic adenocarcinoma remains controversial. This study aimed to investigate the causal relationship between tea consumption and risk of pancreatic adenocarcinoma and to explore their mediating effects. The two-sample Mendelian randomisation (MR) analysis showed an inverse causal relationship between tea intake and pancreatic adenocarcinoma (OR: 0·111 (0·02, 0·85), P < 0·04). To examine the mediating effects, we explored the potential mechanisms by which tea intake reduces the risk of pancreatic adenocarcinoma. Based on the oral bioavailability and drug-like properties in Traditional Chinese Medicine Systems Pharmacology database, we selected the main active ingredients of tea. We screened out the fifteen representative targeted genes by Pharmmapper database, and the gene ontology enrichment analysis showed that these targeted genes were related to vascular endothelial growth factor (VEGF) pathway. The two-step MR analysis of results showed that only VEGF-D played a mediating role, with a mediation ratio of 0·230 (0·066, 0·394). In conclusion, the findings suggest that VEGF-D mediates the effect of tea intake on the risk of pancreatic adenocarcinoma.
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Affiliation(s)
- Yonghao Ouyang
- Research Institute of General Surgery, Jinling Hospital, Nanjing210000, People's Republic of China
| | - Beini Zhou
- Jiangxi Modern polytechnic college, Nanchang330000, People's Republic of China
| | - Lihua Chu
- Jinggangshan University, Ji'an3343000, People's Republic of China
| | - Xin Chen
- Jiangxi University Of Traditional Chinese Medicine, Nanchang330000, People's Republic of China
| | - Qiang Hao
- Research Institute of General Surgery, Jinling Hospital, Nanjing210000, People's Republic of China
| | - Jiajia Lei
- College of Food Science & Project Engineering, Wuhan Polytechnic University, Wuhan430023, People's Republic of China
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Khan MA, Sherwani M, Ahmed KS, Ali M, Kumar PA, Tariq J, Christensen L, Bogale N, Schwartz PB, Zafar SN. Morbidity and Mortality Following Surgery for Pancreatic Cancer in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis. J Surg Oncol 2024. [PMID: 39444276 DOI: 10.1002/jso.27946] [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: 06/02/2024] [Revised: 09/11/2024] [Accepted: 09/29/2024] [Indexed: 10/25/2024]
Abstract
BACKGROUND AND OBJECTIVES Measuring postoperative outcomes after complex cancer operations such as pancreatectomy is vital to improve cancer surgery in low- and middle-income countries (LMICs); however, such data is often limited. This study aimed to review existing research and obtain baseline estimates for postoperative mortality and morbidity after pancreatic cancer surgery in LMICs. METHODS PubMed, Embase, Web of Science Core Collection, and Global Index Medicus were systematically searched for original articles published between January 2005 and May 2022. LMICs based studies reporting postoperative mortality, morbidity, and/or length of stay of patients with primary pancreatic tumors undergoing pancreaticoduodenectomy and/or distal pancreatectomy were included. RESULTS Of 18 344 unique titles and abstracts retrieved, 114 studies met the inclusion criteria. Of these, 51 "good" quality studies comprising 7528 patients were included in the meta-analyses. Pooled estimates for pancreatic fistula were 16.6% (95% CI 14.0-19.7, p < 0.001); 16.0% (95% CI 11.1-22.5, p < 0.001) for Clavien-Dindo grade 3 and 4 complications; 13.4% (95% CI 9.8-17.9, p < 0.001) for wound infection; and 4.4% (95% CI 3.3-5.7, p < 0.001) for postoperative mortality. CONCLUSION This is the first systematic review and meta-analysis examining surgical complications after pancreatic surgery in LMICs. We highlight a lack of data and the need to further evaluate surgical outcomes in LMICs.
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Affiliation(s)
- Mustafa Ali Khan
- Medical College, Aga Khan University, Karachi, Pakistan
- Department of Surgery, Houston Methodist Hospital, Houston, Texas, USA
| | | | - Kaleem S Ahmed
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Mubeen Ali
- Medical College, Aga Khan University, Karachi, Pakistan
| | | | - Javeria Tariq
- Medical College, Aga Khan University, Karachi, Pakistan
| | - Leslie Christensen
- Ebling Library, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Netsanet Bogale
- Hawassa University Comprehensive Specialized Hospital-Cancer Treatment Center, Hawassa, Ethiopia
| | - Patrick B Schwartz
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Syed Nabeel Zafar
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
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Zhang X, Li F, Yang H, Xu H, Wang A, Jia Q, Zhang L, Liu L. A novel simple suture method for establishing an orthotopic pancreatic cancer mouse model: a comparative study with two conventional methods. Am J Transl Res 2024; 16:4422-4435. [PMID: 39398607 PMCID: PMC11470369 DOI: 10.62347/judx2512] [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: 12/26/2023] [Accepted: 08/12/2024] [Indexed: 10/15/2024]
Abstract
OBJECTIVE This study aims to evaluate the efficacy of a novel simple suture method in establishing an optimal animal model for preclinical research in pancreatic cancer. METHODS To establish a novel simple suture method, the tumor fragment was placed on the tail of the pancreas and securely wrapped into the pancreas, and compared with two conventional methods: the cell injection method and the tumor fragment embedding method. Subsequently, emission tomography/computed tomography scanning, gross anatomy observation, hematoxylin and eosin staining, and immunohistochemistry staining were performed to assess the effectiveness of these methods. RESULTS The emission tomography/computed tomography scanning and anatomical examinations confirmed the successful construction of orthotopic pancreatic cancer models using all three methods. Histopathological analysis of the orthotopic masses and metastatic lesions revealed malignant transformation with tumor infiltration into normal tissue. Comparative analysis demonstrated that the cell injection method was easy to perform but resulted in poor uniformity of tumor size and had high costs. The tumor fragment embedding method exhibited excellent uniformity of tumor size, with the highest tumor growth rates and a greater pancreatic impairment. In contrast, the novel simple suture method featured a relatively simple surgical procedure, slower growth rates, good uniformity of tumor size, and minimal pancreatic impairment. CONCLUSION The novel simple suture method is the optimal protocol for establishing an orthotopic pancreatic cancer mouse model, providing a robust foundation for preclinical studies on pancreatic cancer.
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Affiliation(s)
- Xiaotong Zhang
- Department of Immunology, Chengde Medical UniversityChengde 067000, Hebei, P. R. China
| | - Fan Li
- Department of Immunology, Chengde Medical UniversityChengde 067000, Hebei, P. R. China
| | - Hongbin Yang
- Department of Immunology, Chengde Medical UniversityChengde 067000, Hebei, P. R. China
| | - Hailan Xu
- Department of Oncology, The Affiliated Hospital of Chengde Medical UniversityChengde 067000, Hebei, P. R. China
| | - Aihui Wang
- Department of Nuclear Medicine, The Affiliated Hospital of Chengde Medical UniversityChengde 067000, Hebei, P. R. China
| | - Qichen Jia
- Department of Nuclear Medicine, The Affiliated Hospital of Chengde Medical UniversityChengde 067000, Hebei, P. R. China
| | - Li Zhang
- Department of Oncology, The Affiliated Hospital of Chengde Medical UniversityChengde 067000, Hebei, P. R. China
| | - Lei Liu
- Department of Immunology, Chengde Medical UniversityChengde 067000, Hebei, P. R. China
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Xu Y, Yang F, Fu D. Prognostic value of para-aortic lymph node metastasis and dissection for pancreatic head ductal adenocarcinoma: a retrospective cohort study. JOURNAL OF PANCREATOLOGY 2024; 7:199-206. [DOI: 10.1097/jp9.0000000000000159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2025] Open
Abstract
Background:
Para-aortic lymph node (PALN) metastasis affects approximately 20% of patients with pancreatic ductal adenocarcinoma (PDAC). However, the prognostic significance of PALN metastases and dissection remains unclear.
Methods:
This retrospective cohort study included patients with PDAC of the pancreatic head who had undergone pancreaticoduodenectomy (PD) at our center between January 2017 and December 2020.
Results:
A total of 234 patients were included in the study. PALN dissection improved the median overall survival (OS) without statistical significance (24.1 vs 18.1 months, P = .156). The median recurrence-free survival was significantly longer in the PALN-dissection group than the group without PALN dissection (18.2 vs 11.6 months, P = .040). Conversely, there were no significant differences in the long-term prognosis between the PALN-positive and PALN-negative subgroups in the PALN-dissection group. Multivariate analysis showed that PALN metastasis was not an independent risk factor for OS (hazard ratio: 0.831, 95% confidence interval: 0.538–1.285, P = .406).
Conclusions:
For patients with pancreatic head ductal adenocarcinoma, PD with PALN dissection may achieve survival prolongation and bridge the survival gap between patients with and without PALN metastasis without significantly increasing the perioperative risks.
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Affiliation(s)
- Yecheng Xu
- Department of Pancreatic Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Feng Yang
- Department of Pancreatic Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Deliang Fu
- Department of Pancreatic Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
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Zhao H, Zhang Y, Liu H, Wang Y, Song Z. Age-period-cohort analysis of global, regional, and national pancreatic cancer incidence, mortality, and disability-adjusted life years, 1990-2019. BMC Cancer 2024; 24:1063. [PMID: 39198814 PMCID: PMC11350939 DOI: 10.1186/s12885-024-12835-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 08/20/2024] [Indexed: 09/01/2024] Open
Abstract
BACKGROUND Pancreatic cancer is one of the deadliest cancers in the world. In recent years, the incidence and mortality rates of pancreatic cancer have shown an increasing trend year by year. This study investigates the independent effects of age, period, and cohort on the global incidence, mortality, and disability-adjusted life years (DALYs) of pancreatic cancer from 1990 to 2019, and evaluates the differences in the burden of pancreatic cancer across regions with different Sociodemographic Index (SDI) levels. METHODS Estimating the impact of age, period, and cohort on pancreatic cancer disease burden in different SDI regions using age-period-cohort modeling with data (with 95% uncertainty intervals [UI]) from the Global Burden of Disease (GBD) Study 2019 and net drift of age-standardized incidence rates (ASIR), age-standardized mortality rates (ASMR), and age-standardized DALY rates (ASDR) for pancreatic cancer in 120 countries. RESULTS The number of new cases of pancreatic cancer worldwide increased from 197,348 (95% UI: 188,604,203,971) in 1990 to 530,297 (486,175,573,635) in 2019, the number of deaths increased from 198,051 (189,329 to 204,763) in 1990 to 531,107 (491,948 to 566,537) in 2019, and the number of DALY increased from 4,647,207 (4,465,440 to 4,812,129) in 1990 to 11,549,016 (10,777,405 to 1,238,912) in 2019. The ASIR of the average levels in global pancreatic cancer increased from 5.22 (4.97 to 5.40) per 100,000 population to 6.57 (6.00 to 7.09) per 100,000 population, the ASMR increased from 5.34 (5.07 to 5.52) per 100,000 population to 6.62 (6.11 to 7.06) per 100,000 population, and the ASDR increased from 115.47 (110.82 to 119.60) per 100,000 population to 139.61 (130.18 to 149.14) per 100,000 population. The incidence, mortality, and DALY rates of pancreatic cancer increase with age globally and across all SDI regions, peaking in the 85-89 age group. In high and high-middle SDI regions, the growth rate for males is higher than for females before the age of 85, while females have a higher growth rate after 85. The 75-79 age group exhibits the highest DALY rate in high and high-middle SDI regions, significantly higher than the global and other SDI regions. From 1990 to 2019, the period effects of pancreatic cancer incidence, mortality, and DALY rates have increased significantly worldwide, while remaining almost unchanged in high and high-middle SDI regions. In contrast, period effects have significantly increased in middle, low-middle, and low SDI regions. Cohort effects are more pronounced in middle, low-middle, and low SDI regions. CONCLUSIONS With the aggravation of population aging, the incidence and mortality rates of pancreatic cancer in the world are increasing, and effective prevention and control measures can be achieved by reducing the exposure of risk factors. The APC model used in our analysis provides a novel approach to understanding the complex trends in the incidence, mortality, and disability-adjusted life years of pancreatic cancer. It can inform the development of targeted interventions to reduce the severe disease burden caused by pancreatic cancer.
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Affiliation(s)
- Haoran Zhao
- Department of Hepatobiliary and Pancreatic Surgery, Harbin Medical University Cancer Hospital, Harbin City, Heilongjiang Province, People's Republic of China
| | - Yubao Zhang
- Department of Hepatobiliary and Pancreatic Surgery, Harbin Medical University Cancer Hospital, Harbin City, Heilongjiang Province, People's Republic of China
| | - Haishi Liu
- Department of Hepatobiliary and Pancreatic Surgery, Harbin Medical University Cancer Hospital, Harbin City, Heilongjiang Province, People's Republic of China
| | - Yunfeng Wang
- Department of Hepatobiliary and Pancreatic Surgery, Harbin Medical University Cancer Hospital, Harbin City, Heilongjiang Province, People's Republic of China
| | - Zengfu Song
- Department of Hepatobiliary and Pancreatic Surgery, Harbin Medical University Cancer Hospital, Harbin City, Heilongjiang Province, People's Republic of China.
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Wang X, Yu Q, Bai X, Li X, Sun Y, Peng X, Zhao R. The role of the purinergic ligand-gated ion channel 7 receptor in common digestive system cancers. Eur J Cancer Prev 2024; 33:271-281. [PMID: 37942897 DOI: 10.1097/cej.0000000000000851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2023]
Abstract
The incidence of digestive malignancies has increased in recent years, including colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pancreatic cancer. Advanced stages of these cancers are prone to metastasis, which seriously reduce the standard of living of patients and lead to decline in the survival rate of patients. So far there are no good specific drugs to stop this phenomenon. It is very important and urgent to find new biomarkers and therapeutic targets. Purinergic ligand-gated ion channel 7 receptor (P2X7R) is ATP-gated and nonselective ion channel receptor involved in many inflammatory processes and cancer progression. P2X7R is present in many cancer cells and promotes or inhibits cancer development through signal transduction. Studies have presented that P2X7R plays a role in the proliferation and migration of digestive system cancers, such as CRC, HCC and pancreatic cancer. Therefore, P2X7R may serve as a biomarker or therapeutic target for digestive system cancers. This paper describes the structure and function of P2X7R, and mainly reviews the research progress on the role of P2X7R in CRC, HCC and pancreatic cancer.
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Affiliation(s)
- Xin Wang
- School of Medical Laboratory, Weifang Medical University
- Institutional Key Laboratory of Clinical Laboratory Diagnostics, 12th 5-Year project of Shandong Province, Weifang Medical University, Weifang, Shandong, China
| | - Qingqing Yu
- School of Medical Laboratory, Weifang Medical University
- Institutional Key Laboratory of Clinical Laboratory Diagnostics, 12th 5-Year project of Shandong Province, Weifang Medical University, Weifang, Shandong, China
| | - Xue Bai
- School of Medical Laboratory, Weifang Medical University
- Institutional Key Laboratory of Clinical Laboratory Diagnostics, 12th 5-Year project of Shandong Province, Weifang Medical University, Weifang, Shandong, China
| | - Xinyu Li
- School of Medical Laboratory, Weifang Medical University
- Institutional Key Laboratory of Clinical Laboratory Diagnostics, 12th 5-Year project of Shandong Province, Weifang Medical University, Weifang, Shandong, China
| | - Yanli Sun
- School of Medical Laboratory, Weifang Medical University
- Institutional Key Laboratory of Clinical Laboratory Diagnostics, 12th 5-Year project of Shandong Province, Weifang Medical University, Weifang, Shandong, China
| | - Xiaoxiang Peng
- School of Medical Laboratory, Weifang Medical University
- Institutional Key Laboratory of Clinical Laboratory Diagnostics, 12th 5-Year project of Shandong Province, Weifang Medical University, Weifang, Shandong, China
| | - Ronglan Zhao
- School of Medical Laboratory, Weifang Medical University
- Institutional Key Laboratory of Clinical Laboratory Diagnostics, 12th 5-Year project of Shandong Province, Weifang Medical University, Weifang, Shandong, China
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Xu M, Tang J, Sun Q, Meng J, Chen G, Chang Y, Yao Y, Ji J, Luo H, Chen L, Lu M, Shi W. CENPN contributes to pancreatic carcinoma progression through the MDM2-mediated p53 signaling pathway. Arch Med Sci 2024; 20:1655-1671. [PMID: 39649279 PMCID: PMC11623148 DOI: 10.5114/aoms/171956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 09/06/2023] [Indexed: 12/10/2024] Open
Abstract
Introduction We undertook an in-depth investigation of the data pertaining to pancreatic adenocarcinoma (PAAD) to identify potential targets for the development of precision therapies. Material and methods The construction of a protein-protein interaction (PPI) network was based on overlapping differentially expressed genes (DEGs) identified in the GSE16515, GSE32676, and GSE125158 datasets. A subsequent bioinformatic analysis was performed on the interconnected genes within the PPI network, leading to the identification of the central gene, CENPN. In vitro experimentation such as CCK8 and Transwell experiments was employed to elucidate the impact of CENPN expression patterns on PAAD cell proliferation, migration, and invasion. Furthermore, the investigation revealed through comprehensive enrichment analysis that the pivotal signaling pathway associated with CENPN is the p53 signaling pathway. Results Following a comprehensive bioinformatic analysis of 161 concordant differentially expressed genes (DEGs) across three microarray datasets, CENPN emerged as the central gene under investigation. Overexpression of CENPN in pancreatic adenocarcinoma (PAAD) was associated with unfavorable patient outcomes and heightened sensitivity to four PAAD therapies: gemcitabine, docetaxel, paclitaxel, and sunitinib. Reduced CENPN expression impeded PAAD cell proliferation, migration, and invasion; however, these effects were counteracted upon upregulation of CENPN expression. Additionally, CENPN interacted with MDM2, promoting PAAD progression by targeting the p53 signaling pathway. Conclusions The findings of our study substantiate that CENPN is associated with the pathogenesis of PAAD. Consequently, CENPN appears to be a promising candidate for targeted precision therapy in clinical applications.
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Affiliation(s)
- Ming Xu
- Department of Gastroenterology, Shanghai Pudong New Area People’s Hospital, Shanghai, China
| | - Jie Tang
- Department of Gastroenterology, Shanghai Pudong New Area People’s Hospital, Shanghai, China
| | - Qiong Sun
- Department of Oncology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Jing Meng
- Department of Oncology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Guoyu Chen
- Department of Gastroenterology, Shanghai Pudong New Area People’s Hospital, Shanghai, China
| | - Yunli Chang
- Department of Gastroenterology, Shanghai Pudong New Area People’s Hospital, Shanghai, China
| | - Yao Yao
- Department of Gastroenterology, Shanghai Pudong New Area People’s Hospital, Shanghai, China
| | - Jieru Ji
- Department of Gastroenterology, Shanghai Pudong New Area People’s Hospital, Shanghai, China
| | - Hao Luo
- Department of Gastroenterology, Shanghai Pudong New Area People’s Hospital, Shanghai, China
| | - Lingling Chen
- Department of Gastroenterology, Shanghai Pudong New Area People’s Hospital, Shanghai, China
| | - Minxue Lu
- Department of Gastroenterology, Huzhou College Affiliated Nantaihu Hospital, Huzhou, Zhejiang, China
| | - Weiwei Shi
- Department of Oncology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
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Ramai D, Smith ER, Wang Y, Huang Y, Obaitan I, Chandan S, Dhindsa B, Papaefthymiou A, Morris JD. Epidemiology and Socioeconomic Impact of Pancreatic Cancer: An Analysis of the Global Burden of Disease Study 1990-2019. Dig Dis Sci 2024; 69:1135-1142. [PMID: 38383939 DOI: 10.1007/s10620-024-08292-1] [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: 09/09/2023] [Accepted: 01/10/2024] [Indexed: 02/23/2024]
Abstract
INTRODUCTION The aim of this study is to estimate the global burden of pancreatic cancer from 1990 to 2019. METHODS We reconstructed the Global Burden of Diseases (GBD) study results for pancreatic cancer across 204 countries and territories. Our study generated estimates for key disease burden indicators, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs), and cost. Linear regression analysis of the natural logarithm of age-standardized outcomes was used to calculate annual percent change. RESULTS In 2019, there were a total of 530,296 incident and 442,101 prevalent cases of pancreatic cancer, resulting in 531,107 deaths and 11.5 million DALYs lost. The age-standardized incidence and prevalence of pancreatic cancer has increased from 5.22 (95% CI 4.97-5.40) to 6.57 (CI 6.00-7.09) per 100,000 people per year, and 4.1 (95% CI 3.95-4.26) to 5.4 (CI 4.96-5.87), respectively. This equated to 10 million (95% CI 9.5 to 10.4 million) incident cases of pancreatic cancer. The number of DALYs lost as a result of pancreatic cancer was 225 million years (95% CI 216-234 million years). Mortality from pancreatic cancer increased over the study period from 3.7 (95% CI 3.54-3.83) to 6.9 (95% CI 6.36-7.32). Incidence, prevalence, DALYs, and mortality were higher in countries with a higher socio-demographic index. CONCLUSIONS Pancreatic cancer is rising around the world and is associated with a high economic burden. Programs aimed at reducing modifiable risk factors are needed.
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Affiliation(s)
- Daryl Ramai
- Division of Gastroenterology, Hepatology, and Nutrition, University of Utah Health, Salt Lake City, UT, USA.
| | - Eric R Smith
- Department of Medicine, Baylor Scott & White Health, Round Rock, TX, USA
| | - Yichen Wang
- Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Yuting Huang
- Division of Gastroenterology and Hepatology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Itegbemie Obaitan
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Saurabh Chandan
- Division of Gastroenterology, Creighton University School of Medicine, Creighton University, Omaha, NE, USA
| | - Banreet Dhindsa
- Division of Gastroenterology and Hepatology, NYU Langone, New York, NY, USA
| | | | - John D Morris
- Division of Gastroenterology, Hepatology, and Nutrition, University of Utah Health, Salt Lake City, UT, USA
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Luo C, Yu Y, Zhu J, Chen L, Li D, Peng X, Liu Z, Li Q, Cao Q, Huang K, Yuan R. Deubiquitinase PSMD7 facilitates pancreatic cancer progression through activating Nocth1 pathway via modifying SOX2 degradation. Cell Biosci 2024; 14:35. [PMID: 38494478 PMCID: PMC10944620 DOI: 10.1186/s13578-024-01213-9] [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: 11/02/2023] [Accepted: 02/27/2024] [Indexed: 03/19/2024] Open
Abstract
BACKGROUND Ubiquitination is a critical post-translational modification which can be reversed with an enzyme family known as deubiquitinating enzymes (DUBs). It has been reported that dysregulation of deubiquitination leads to carcinogenesis. As a member of the DUBs family, proteasome 26 S subunit non-ATPase 7 (PSMD7) serves as an underlying tumour-promoting factor in multiple cancers. However, the clinical significance and biological functions of PSMD7 in pancreatic cancer (PC) remain unclear. RESULTS In this study, we first reported frequent overexpression of PSMD7 in PC tissues, and high levels of PSMD7 were markedly linked to shorter survival and a malignant phenotype in PC patients. An array of in vitro and in vivo gain/loss-of-function tests revealed that PSMD7 facilitates the progression of PC cells. Additionally, we found that PSMD7 promotes PC cell progression by activating the Notch homolog 1 (Notch1) signalling. Interestingly, in PC cells, the inhibitory effect of PSMD7 knockdown on cellular processes was comparable to that observed upon Notch1 knockdown. Mechanistically, PSMD7 deubiquitinated and stabilised sex determining region Y (SRY)-box 2 (SOX2), a key mediator of Notch1 signalling. The stabilisation of SOX2, mediated by PSMD7, dramatically increased SOX2 protein levels, subsequently activating the Notch1 pathway. Finally, restoration of SOX2 expression abrogated the PSMD7-silenced antitumour effect. CONCLUSIONS Taken together, our work identifies and validates PSMD7 as a promoter of PC progression through augmentation of the Notch1 signalling pathway mediated by SOX2. This finding suggests that PSMD7 holds promise as a potential therapeutic target for the management of this refractory disease.
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Affiliation(s)
- Chen Luo
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330006, China
- Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, 330006, China
| | - Yi Yu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330006, China
- Department of Urology Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330006, China
| | - Jinfeng Zhu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330006, China
- Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, Hunan Province, 410219, China
| | - Leifeng Chen
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330006, China
| | - Dan Li
- Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330006, China
| | - Xingyu Peng
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330006, China
| | - Zitao Liu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330006, China
| | - Qing Li
- Department of Pathology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330006, China
| | - Qing Cao
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330006, China
| | - Kai Huang
- Department of General Surgery, Jiangxi Provincial Cancer Hospital, Nanchang, Jiangxi Province, 330029, China
| | - Rongfa Yuan
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330006, China.
- Jiangxi Provincial Clinical Research Center for General Surgery Disease, Nanchang, Jiangxi Province, 330006, China.
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11
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Saraswat SK, Mahmood BS, Ajila F, Kareem DS, Alwan M, Athab ZH, Shaier JB, Hosseinifard SR. Deciphering the oncogenic landscape: Unveiling the molecular machinery and clinical significance of LncRNA TMPO-AS1 in human cancers. Pathol Res Pract 2024; 255:155190. [PMID: 38330619 DOI: 10.1016/j.prp.2024.155190] [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: 01/14/2024] [Revised: 01/30/2024] [Accepted: 01/31/2024] [Indexed: 02/10/2024]
Abstract
The in-depth exploration of long non-coding RNAs (lncRNAs) reveals their pivotal and diverse roles in various disorders, particularly cancer. Within this intricate landscape, thymopoietin-antisense RNA-1 (TMPO-AS1) emerges as a noteworthy instigator of oncogenesis in humans. This exhaustive review seeks to intricately unravel the present understanding of TMPO-AS1, emphasizing its molecular foundations and highlighting its clinical applications in the realm of cancer research. TMPO-AS1 consistently exhibits heightened expression across a spectrum of cancer types, encompassing lung, colorectal, breast, cervical, bladder, pancreatic, hepatocellular, gastric, ovarian, and osteosarcoma. Elevated levels of TMPO-AS1 are intricately linked to unfavorable prognoses, accompanied by distinctive clinical and pathological characteristics. Functionally, TMPO-AS1 showcases its prowess in enhancing cancer cell migration, invasion, proliferation, and orchestrating epithelial-mesenchymal transition (EMT) through a myriad of molecular mechanisms. These mechanisms entail intricate interactions with proteins, microRNAs, and intricate signaling pathways. Furthermore, TMPO-AS1 is intricately involved in regulating critical cellular processes, including apoptosis and the cell cycle. The mounting evidence converges towards the potential of TMPO-AS1 serving as a diagnostic and prognostic biomarker, further entwined with its potential role in influencing chemoresistance in cancer. This potential is underscored by its consistent associations with clinical outcomes and treatment responses. This comprehensive investigation not only consolidates our existing knowledge of TMPO-AS1's multifaceted roles but also sheds illuminating insights on its profound significance in the intricate landscape of cancer biology, paving the way for potential applications in clinical practice.
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Affiliation(s)
| | | | - Freddy Ajila
- Facultad de Informática y Electrónica, Escuela Superior Politécnica de Chimborazo (ESPOCH), Sede Orellana, El Coca 220001, Ecuador.
| | | | - Mariem Alwan
- Medical Technical College, Al-Farahidi University, Iraq
| | - Zainab H Athab
- Department of Pharmacy, Al-Zahrawi University College, Karbala, Iraq
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12
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Bao Y, Zhang M, Wu P, Wang Y, Wan B, Li X, Ding H. Cost-effectiveness of open pancreaticoduodenectomy with or without Heidelberg TRIANGLE operation for pancreatic cancer in China. J Cancer Res Clin Oncol 2023; 149:16705-16715. [PMID: 37726557 DOI: 10.1007/s00432-023-05406-6] [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: 07/07/2023] [Accepted: 09/04/2023] [Indexed: 09/21/2023]
Abstract
OBJECTIVE Pancreatic cancer is a digestive malignancy with dismal prognosis. The advent of Heidelberg TRIANGLE dissection technique brings a turning point to improve the chance of survival. Our study aimed to evaluated the cost-effectiveness of open pancreaticoduodenectomy (OPD) versus OPD combined with TRIANGLE operation (OPD-TRIANGLE) for patients with pancreatic cancer from the perspective of healthcare system in China. METHODS Two hundred forty-six patients with pancreatic cancer who underwent OPD or OPD-TRIANGLE from January to September 2022 were enrolled in this study. We performed a decision tree model to assess clinical and economic implications of different surgical strategies. Estimation of health utilities was based on published literature, while costs were acquired from the hospitals, clinical expert consultations, and other local charge. The incremental cost-effectiveness ratio (ICER) was regarded as the primary outcome. Uncertainty of the findings was addressed via sensitivity analyses and scenario analyses. RESULTS The results indicated that OPD-TRIANGLE group yielded additional 0.0402 QALYs at an incremental cost of US$1501.83 compared with OPD group, and the corresponding ICER was US$37,358.96 per QALY. The probabilities of OPD-TRIANGLE as the prior option were 52.8% at the WTP threshold of 60,000 US$/QALY. The main factors lined with costs incorporating total medical costs and operation-related costs. With 5-20% price reduction of OPD-TRIANGLE, the outcomes were also economically attractive. CONCLUSION The findings of this population-based study suggested that OPD-TRIANGLE was likely to be cost-effective for patients with pancreatic cancer when compared against OPD. Further in-depth studies should be conducted to provide more comprehensive evidence.
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Affiliation(s)
- Yuwen Bao
- School of Health Policy and Management, Nanjing Medical University, No. 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China
| | - Mengdie Zhang
- School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China
| | - Pengfei Wu
- Pancreas Center, The First Affiliated Hospital with Nanjing Medical University (Jiangsu Province Hospital) Pancreas Institute of Nanjing Medical University, Nanjing, 210029, China
| | - Yingpeng Wang
- Department of Health Insurance Management, The First Affiliated Hospital with Nanjing Medical University (Jiangsu Province Hospital), 300 Guangzhou Road, Gulou District, Nanjing, 210029, China
| | - Bin Wan
- Department of Health Insurance Management, The First Affiliated Hospital with Nanjing Medical University (Jiangsu Province Hospital), 300 Guangzhou Road, Gulou District, Nanjing, 210029, China
| | - Xin Li
- School of Health Policy and Management, Nanjing Medical University, No. 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China.
- School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
| | - Haixia Ding
- Department of Health Insurance Management, The First Affiliated Hospital with Nanjing Medical University (Jiangsu Province Hospital), 300 Guangzhou Road, Gulou District, Nanjing, 210029, China.
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Liang J, Cao H, Wang G, Wei L, Dong L, Chen G, Li Q, Zhu D. TMPOP2 Inhibition Suppresses Pancreatic Cancer Cell Migration and Development by Repressing The JNK/STAT3 Pathway. Adv Biol (Weinh) 2023; 7:e2300113. [PMID: 37469237 DOI: 10.1002/adbi.202300113] [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: 03/19/2023] [Revised: 06/18/2023] [Indexed: 07/21/2023]
Abstract
Pancreatic cancer is a malignancy with a poor prognosis and high mortality. The lincRNA TMPOP2 is highly expressed in gynecological cancers and may exhibit tumor-promoting functions. However, the function of TMPOP2 in pancreatic cancer is limited. TMPOP2 expression in pancreatic cancer and adjacent tissues is analyzed from The Cancer Genome Atlas (TCGA) and GTEx database. It shows the high expression of TMPOP2 in pancreatic cancer tissues. Similar results are observed in resected pancreatic adenocarcinoma tumors and adjacent tissues from 20 patients and the relative cell lines. When the pancreatic cell lines are transfected with si-TMPOP2, it shows that TMPOP2 downregulation inhibits the cells migration and EMT. Furthermore, the potential mechanism is explored by detecting the expression of c-Jun N-terminal kinase (JNK), phosphorylated JNK, signal transducer and activator of transcription 3 (STAT3), and phosphorylated STAT3. It suggests that TMPOP2 knockdown inactivates JNK and STAT3 phosphorylation. When a JNK activator (anisomycin) is added to the cells with si-NC or si-TMPOP2, it can partially reverse the migration and EMT inhibition of the cells with inhibited TMPOP2. TMPOP2 inhibition suppresses the migration and EMT of pancreatic cancer by repressing the JNK/STAT3 pathway. Thus, this may be a novel target for pancreatic cancer therapy.
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Affiliation(s)
- Jun Liang
- Department of Oncology Medicine Center, Shanghai East Hospital, School of Medicine,Tongji University, Shanghai, 200092, China
| | - Huangming Cao
- Department of Oncology, East Hospital, Tongji University School of Medicine, 1800 Yuntai Road, Shanghai, 200123, China
| | - Guangxue Wang
- Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China
| | - Liang Wei
- Department of Neurosurgery, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China
| | - Lin Dong
- Department of Cardiothoracic Surgery, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China
| | - Guohan Chen
- Department of Cardiothoracic Surgery, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China
| | - Qinchuan Li
- Department of Cardiothoracic Surgery, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China
| | - Dongyi Zhu
- Department of Respiratory Medicine, East Hospital, Tongji University School of Medicine, 1800 Yuntai Road, Shanghai, 200123, China
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Cao F, Li F, Shi L, Zhang G, Zhang L, Ma T, Zhang K. Spatial and Temporal Trends in Pancreatic Cancer Burden Attributable to High Body Mass Index at the Global and National Levels. J Epidemiol Glob Health 2023; 13:831-841. [PMID: 37796406 PMCID: PMC10686914 DOI: 10.1007/s44197-023-00155-8] [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: 05/30/2023] [Accepted: 09/14/2023] [Indexed: 10/06/2023] Open
Abstract
OBJECTIVES To examine the spatiotemporal trends in pancreatic cancer (PC) disability-adjusted life years (DALYs) and mortality attributable to high body-mass index (BMI) by age, gender, and countries from 1990 to 2019. METHODS Data were extracted from the Global Burden of Disease Study 2019 results. We presented the annual number of PC DALYs and mortality, and corresponding age-standardized rates (ASDR and ASMR), which were further stratified by age, gender, and countries. The estimated annual percentage change (EAPC) was computed to assess the longitudinal trends in ASRs. RESULTS In 2019, 0.7 million DALYs and 31.9 thousand deaths worldwide were caused by PC attributable to high BMI, with the largest amount reported in high-income North America, Western Europe, and East Asia. The corresponding ASDR and ASMR were highest in females and in high SDI regions, while quite varied across countries. The global EAPC in ASDR and ASMR was 1.45 (95% uncertainty interval [UI]: 1.40, 1.50) and 1.44 (95% UI: 1.39, 1.49), respectively. Almost all involved countries demonstrated significant uptrends in ASRs from 1990 to 2019. CONCLUSIONS More productive efforts to reduce the impact of modifiable risk factors, such as overweight, should be undertaken, and thus effectively curb the rise of PC burden.
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Affiliation(s)
- Fei Cao
- Department of Oncology, Luohe Central Hospital, People's East Road 54, Luohe City, 462000, Henan Province, China
| | - Feng Li
- Department of General Surgery, Shaoling District People's Hospital of Luohe, Luohe City, 462000, Henan Province, China
| | - Lei Shi
- Department of Oncology, Luohe Central Hospital, People's East Road 54, Luohe City, 462000, Henan Province, China
| | - Guoyao Zhang
- Department of Oncology, Luohe Central Hospital, People's East Road 54, Luohe City, 462000, Henan Province, China
| | - Lei Zhang
- Department of Oncology, Luohe Central Hospital, People's East Road 54, Luohe City, 462000, Henan Province, China
| | - Tianjiang Ma
- Department of Oncology, Luohe Central Hospital, People's East Road 54, Luohe City, 462000, Henan Province, China
| | - Kexun Zhang
- Department of Infectious Disease Control, Kunshan Centers for Disease Control and Prevention, Tongcheng South Road 567, Kunshan, 215300, Jiangsu, China.
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15
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Zhang ZH, Bao YW, Zhao YJ, Wang JQ, Guo JT, Sun SY. Circulating tumor cells as potential prognostic biomarkers for early-stage pancreatic cancer: A systematic review and meta-analysis. World J Clin Oncol 2023; 14:504-517. [PMID: 38059182 PMCID: PMC10696218 DOI: 10.5306/wjco.v14.i11.504] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 09/14/2023] [Accepted: 10/26/2023] [Indexed: 11/22/2023] Open
Abstract
BACKGROUND Pancreatic cancer is difficult to be diagnosed early clinically, while often leads to poor prognosis. If optimal personalized treatment plan can be provided to pancreatic cancer patient at an earlier stage, this can greatly improve overall survival (OS). Circulating tumor cells (CTCs) are a collective term for various types of tumor cells present in the peripheral blood (PB), which are formed by detachment during the development of solid tumor lesions. Most CTCs undergo apoptosis or are phagocytosed after entering the PB, whereas a few can escape and anchor at distal sites to develop metastasis, increasing the risk of death for patients with malignant tumors. AIM To investigate the significance of CTCs in predicting the prognosis of early pancreatic cancer patients. METHODS The PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine, and ChinaInfo databases were searched for articles published through December 2022. Studies were considered qualified if they included patients with early pancreatic cancer, analyzed the prognostic value of CTCs, and were full papers reported in English or Chinese. Researches were selected and assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol and the Newcastle-Ottawa Scale criteria. We used a funnel plot to assess publication bias. RESULTS From 1595 publications, we identified eight eligible studies that collectively enrolled 355 patients with pancreatic cancer. Among these original studies, two were carried out in China; three in the United States; and one each in Italy, Spain, and Norway. All eight studies analyzed the relevance between CTCs and the prognosis of patients with early-stage pancreatic cancer after surgery. A meta-analysis showed that the patients that were positive pre-treatment or post-treatment for CTCs were associated with decreased OS [hazard ratio (HR) = 1.93, 95% confidence interval (CI): 1.197-3.126, P = 0.007] and decreased relapse-free/disease-free/progression-free survival (HR = 1.27, 95%CI: 1.137-1.419, P < 0.001) in early-stage pancreatic cancer. Additionally, the results suggest no statistically noticeable publication bias for overall, disease-free, progression-free, and recurrence-free survival. CONCLUSION This pooled meta-analysis shows that CTCs, as biomarkers, can afford reliable prognostic information for patients with early-stage pancreatic cancer and help develop individualized treatment plans.
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Affiliation(s)
- Zi-Han Zhang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Yi-Wen Bao
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Ya-Jun Zhao
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Jian-Quan Wang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Jin-Tao Guo
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Si-Yu Sun
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
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Zhang Y, Zheng F, Wang F, Liu X, Xiang C, Fu S, Shen K, Liu G. The Expression of Two Distinct Sets of Glycolytic Enzymes Reveals Differential Effects of Glycolytic Reprogramming on Pancreatic Ductal Tumorigenesis in Mice. Biomedicines 2023; 11:2962. [PMID: 38001963 PMCID: PMC10669313 DOI: 10.3390/biomedicines11112962] [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: 09/04/2023] [Revised: 10/17/2023] [Accepted: 10/31/2023] [Indexed: 11/26/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is associated with enhanced aerobic glycolysis through elevated glucose uptake and the upregulated expression of genes encoding rate-limiting glycolytic enzymes. However, the direct impact of altered glycolytic pathways on pancreatic tumor progression has not been thoroughly investigated. Here, we utilized two strains of BAC transgenic mice with pancreatic expression of two distinct sets of glycolytic genes each arranged in a polycistronic fashion (PFKFB3-HK2-GLUT1 and LDHA-PDK1, respectively) to investigate the role of altered glycolysis on the development of pancreatic ductal tumor development in the Pdx1-Cre; LSL-KrasG12D mice. The overexpression of the two sets of glycolytic genes exhibited no significant effects on tumor development in the 4-5-month-old mice (the PanIN2 lesions stage). In the 9-10-month-old mice, the overexpression of PFKFB3-HK2-GLUT1 significantly accelerated PanIN3 progression, exhibiting elevated levels of ductal cell marker CK19 and tumor fibrosis. Surprisingly, the overexpression of LDHA-PDK1 significantly attenuated the progression of PanIN3 in the 9-10-month-old mice with significantly downregulated levels of CK19 and fibrosis. Therefore, distinct set of glycolytic enzymes that are involved in different glycolytic routes exhibited contrasting effects on pancreatic ductal tumor development depending on the tumor stages, providing novel insights into the complexity of the glycolytic pathway in the perspective of PDAC development and therapy.
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Affiliation(s)
| | | | | | | | | | | | | | - Geng Liu
- State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, 12 Xuefu Road, Pukou High-Tech District, Nanjing 210061, China; (Y.Z.); (F.Z.); (F.W.); (X.L.); (C.X.); (S.F.); (K.S.)
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Lu J, Yang Y, Liu X, Chen X, Song W, Liu Z. FTO-mediated LINC01134 stabilization to promote chemoresistance through miR-140-3p/WNT5A/WNT pathway in PDAC. Cell Death Dis 2023; 14:713. [PMID: 37914721 PMCID: PMC10620239 DOI: 10.1038/s41419-023-06244-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 10/13/2023] [Accepted: 10/23/2023] [Indexed: 11/03/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer most frequently detected at an advanced stage that limits treatment options to systemic chemotherapy, which has provided only marginal positive clinical outcomes. Currently, the first-line chemotherapeutic agent for PDAC is gemcitabine (GEM). However, the chemotherapy resistance to GEM is often overlooked in the clinical treatment of PDAC due to the lack of effective biological markers. Therefore, it is crucial to find new prognostic markers and therapeutic targets for patients with PDAC. In this study, we identified a novel regulatory mechanism in the development of resistance to GEM in PDAC. Here, we report that LINC01134 was significantly upregulated in primary tumors from PDAC patients. In vitro and in vivo functional studies revealed that LINC01134 promotes PDAC resistance to GEM through facilitating stem cell features and modulating the cell cycle. Mechanistically, LINC01134 interactes with tumor suppressor miR-497-5p in PDAC cells. Increased LINC01134 downregulates miR-140-3p to promotes the oncogenic WNT5A expression. Moreover, m6A demethylase FTO participated in the upregulation of LINC01134 by maintaining LINC01134 mRNA stability through YTHDF2. Taken together, the present study suggested FTO-mediated LINC01134 stabilization to promote chemotherapy resistance to GEM through miR-140-3p/WNT5A/WNT pathway in PDAC. Our study identified new prognostic markers and new therapeutic targets for patients with PDAC.
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Affiliation(s)
- Jin Lu
- Cancer Center, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, China
| | - Yongsheng Yang
- Department of Hepatobiliary Pancreatic Surgery, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun, 130041, China
| | - Xiangliang Liu
- Cancer Center, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, China
| | - Xiao Chen
- Cancer Center, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, China
| | - Wei Song
- Cancer Center, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, China
| | - Zefeng Liu
- Department of Hepatobiliary Pancreatic Surgery, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun, 130041, China.
- Jilin Engineering Laboratory for Translational Medicine of Hepatobiliary and Pancreatic Diseases, Changchun, 130041, China.
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Wang H, Li Y, Huang J, Ma Y, Lyu S, Lang R. Prognostic value of perioperative serum low-density lipoprotein cholesterol level for postoperative prognosis of pancreatic cancer: a retrospective study. Lipids Health Dis 2023; 22:88. [PMID: 37391827 DOI: 10.1186/s12944-023-01851-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 06/16/2023] [Indexed: 07/02/2023] Open
Abstract
BACKGROUND As a common malignant tumour, pancreatic cancer (PC) has the worst clinical outcome. Early evaluation of the postoperative prognosis has certain clinical value. Low-density lipoprotein cholesterol (LDL-c), which is mainly composed of cholesteryl esters, phospholipids, and proteins, plays an important role in transporting cholesterol into peripheral tissues. LDL-c has also been reported to be correlated with the occurrence and progression of malignant tumours and can predict postoperative prognosis in various tumours. AIMS To determine correlation between serum LDL-c level and clinical outcome in PC patients after surgery. METHODS Data of PC patients that received surgery at our department from January 2015 to December 2021 were retrospectively analysed. Receiver operating characteristic (ROC) curves between perioperative serum LDL-c at different timepoints and survival rate at postoperative 1-year were drawn, and the optimal cut-off value was calculated. Patients were categorized into low and high LDL-c groups, and their clinical data and outcome were compared. Univariate and multivariate analyses were applied to screen out risk markers for poor prognosis of PC patients after surgery. RESULTS The area under the ROC curve of serum LDL-c at 4 weeks after surgery and prognosis was 0.669 (95% CI: 0.581-0.757), and the optimal cut-off value was 1.515 mmol/L. The median disease-free survival (DFS) rates of low and high LDL-c groups were 9 months and 16 months, respectively, and the 1-, 2- and 3-year DFS rates were 42.6%, 21.1% and 11.7% in low LDL-c group, respectively, and, 60.2%, 35.3% and 26.2% in high LDL-c group, respectively (P = 0.005). The median overall survival (OS) rates of low and high LDL-c groups were 12 months and 22 months, respectively, and the 1-, 2- and 3-year OS rates were 46.8%, 22.6% and 15.8% in low LDL-c group, respectively, and 77.9%, 46.8% and 30.4% in high LDL-c group, respectively (P = 0.004). Multivariate analysis confirmed low postoperative 4-week serum LDL-c as independent risk marker for early tumour recrudesce and poor clinical outcome in PC patients. CONCLUSION High postoperative 4-week serum LDL-c is a prognostic marker for prolonged DFS and OS time in PC patients.
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Affiliation(s)
- Hanxuan Wang
- Hepatobiliary Surgery Department, Beijing Chao-Yang Hospital, Beijing, No. 8 Gongti South Road, Chao-Yang District, 100020, China
| | - Yulin Li
- Hepatobiliary Surgery Department, Beijing Chao-Yang Hospital, Beijing, No. 8 Gongti South Road, Chao-Yang District, 100020, China
| | - Jincan Huang
- Hepatobiliary Surgery Department, Beijing Chao-Yang Hospital, Beijing, No. 8 Gongti South Road, Chao-Yang District, 100020, China
| | - Youwei Ma
- Hepatobiliary Surgery Department, Beijing Chao-Yang Hospital, Beijing, No. 8 Gongti South Road, Chao-Yang District, 100020, China
| | - Shaocheng Lyu
- Hepatobiliary Surgery Department, Beijing Chao-Yang Hospital, Beijing, No. 8 Gongti South Road, Chao-Yang District, 100020, China.
| | - Ren Lang
- Hepatobiliary Surgery Department, Beijing Chao-Yang Hospital, Beijing, No. 8 Gongti South Road, Chao-Yang District, 100020, China.
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Huang X, Zhao C, Han Y, Li S. Establishment and validation of a prognostic signature for pancreatic ductal adenocarcinoma based on lactate metabolism-related genes. Front Mol Biosci 2023; 10:1143073. [PMID: 37363401 PMCID: PMC10288859 DOI: 10.3389/fmolb.2023.1143073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 06/01/2023] [Indexed: 06/28/2023] Open
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancy with poor prognosis. To improve patient outcomes, it is necessary to gain a better understanding of the oncogenesis and progression of this disease. Metabolic reprogramming, particularly the regulation of lactate metabolism, is known to have a significant impact on tumor microenvironment and could provide valuable insights for the management of PDAC patients. In this study, we aimed to investigate the prognostic potential of lactate metabolism-related genes (LMRGs). Methods: Transcriptomic data of patients with PDAC along with the clinical outcomes were retrieved from The Cancer Genome Atlas database, and the expression data in normal pancreas from Genotype-Tissue Expression dataset were adopted as the normal control. By using Cox and LASSO regression models, we identified key genes that are differentially expressed in cancerous tissues and related to prognosis. To determine the prognostic value of LMRGs in PDAC, we evaluated their clinical significance and model performance using both the area under the receiver operator characteristic curve (AUC) and calibration curves. In addition, we evaluated the drug sensitivity prediction and immune infiltration by using oncoPredict algorithm, single sample gene set enrichment analysis and Tumor Immune Estimation Resource. Results: A total of 123 LMRGs were identified through differential gene screening analysis, among which 7 LMRGs were identified to comprise a LMRGs signature that independently predict overall survival of these PDAC patient. The AUC values for the LMRGs signature were 0.786, 0.820, 0.837, and 0.816 for predicting 1-, 2-, 3- and 5-year overall survival respectively. Furthermore, this prognostic signature was used to stratify patients into high-risk and low-risk groups, with the former having worse clinical outcomes. This observation was further validated through analysis of the International Cancer Genome Consortium database. In addition, lower sensitivity to gemcitabine and infiltration of immune effector cells were observed in the cancer tissue of patients in the high-risk group. Conclusion: In conclusion, our data suggests that a genomic signature comprised of these LMRGs may be a novel predictor of overall clinical outcomes and present therapeutic potential for PDAC patients.
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Affiliation(s)
- Xin Huang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
- Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China
- Department of Pancreatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Chongyu Zhao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
- Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China
- Department of Pancreatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yuanxia Han
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
- Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China
- Department of Pancreatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Shengping Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
- Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China
- Department of Pancreatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
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Wang K, Chen Z, Qiao X, Zheng J. LncRNA NORAD regulates the mechanism of the miR-532-3p/Nectin-4 axis in pancreatic cancer cell proliferation and angiogenesis. Toxicol Res (Camb) 2023; 12:425-432. [PMID: 37397924 PMCID: PMC10311138 DOI: 10.1093/toxres/tfad026] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 02/15/2023] [Accepted: 03/30/2023] [Indexed: 07/04/2023] Open
Abstract
Backgound Pancreatic cancer (PC) is one of the deadliest cancers worldwide, and cell proliferation and angiogenesis play an important role in its occurrence and development. High levels of lncRNANORAD have been detected in many tumors, including PC, yet the effect and mechanism of lncRNA NORAD on PC cell angiogenesis are unexplored. Methods qRT.PCR was applied to quantify lncRNA NORAD and miR-532-3p expression in PC cells, and a dual luciferase reporter gene was used to verify the targeting effects of NORAD, miR-532-3p and Nectin-4. Then, we regulated NORAD and miR-532-3p expression in PC cells and detected their effects on PC cell proliferation and angiogenesis using cloning experiments and HUVEC tube formation experiments. Results LncRNA NORAD was upregulated and miR-532-3p was downregulated in PC cells compared with normal cells. Knockdown of NORAD inhibited PC cell proliferation and angiogenesis. LncRNA NORAD and miR-532-3p competitively bound to promote the expression of the miR-532-3p target gene Nectin-4, thereby promoting proliferation and angiogenesis of PC cells in vitro. Conclusion LncRNA NORAD promotes the proliferation and angiogenesis of PC cells by regulating the miR-532-3p/Nectin-4 axis, which may be a potential biological target in the diagnosis and treatment of clinical PC.
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Affiliation(s)
- Kaiqiong Wang
- Department of Hepatobiliary Surgery, Hainan Provincial People's Hospital, No.19, Xiuhua Road, Haikou, Hainan Province 570311, China
| | - Zhiju Chen
- Department of Gastrointestinal Surgery, Hainan Provincial People’s Hospital, No.19, Xiuhua Road, Haikou, Hainan Province 570311, China
| | - Xin Qiao
- Department of Hepatobiliary Surgery, Hainan Provincial People's Hospital, No.19, Xiuhua Road, Haikou, Hainan Province 570311, China
| | - Jinfang Zheng
- Department of Hepatobiliary Surgery, Hainan Provincial People's Hospital, No.19, Xiuhua Road, Haikou, Hainan Province 570311, China
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21
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Chen Y, Chen T, Fang JY. Burden of gastrointestinal cancers in China from 1990 to 2019 and projection through 2029. Cancer Lett 2023; 560:216127. [PMID: 36933779 DOI: 10.1016/j.canlet.2023.216127] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 03/10/2023] [Accepted: 03/13/2023] [Indexed: 03/18/2023]
Abstract
Although gastrointestinal (GI) cancers pose a great challenge to public health, data are scant for understanding the burden of GI cancers in China. We aimed to provide an updated estimate of the burden of major GI cancers in China over three decades. According to the GLOBOCAN 2020 database, 1,922,362 GI cancer cases were newly diagnosed and 1,497,388 deaths occurred in China in 2020, with the highest incidence in colorectal cancer (555,480 new cases; 23.90/100,000 age-standardized incidence rate [ASIR]) and the highest mortality in liver cancer (391,150 deaths; 17.20/100,000 age-standardized mortality rate [ASMR]). The age-standardized rates (ASRs) in incidence, mortality, and disability-adjusted life year (DALY) rates for esophageal, gastric, and liver cancers have declined overall (1990-2019, average annual perventage change [AAPC] < 0%, p < 0.001) but have become flattened or reversed in recent years, alarmingly. The spectrum of GI cancers in China will continue transitioning in the next decade, characterized by rapid increases in colorectal and pancreatic cancers in addition to a high burden of esophageal, gastric, and liver cancers. High body-mass index was found to be the fastest-growing risk factor for GI cancers (estimated annual perventage change [EAPC]: 2.35%-3.20%, all p < 0.001), whereas smoking and alcohol consumption remained the top contributors to GI cancer-related deaths in men. In conclusion, GI cancers in China are challenging the healthcare system with a growing burden and a transitioning pattern. Comprehensive strategies are needed to reach the Healthy China 2030 target.
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Affiliation(s)
- Youli Chen
- State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200001, China
| | - Tianhui Chen
- Department of Cancer Prevention, Zhejiang Cancer Hospital, Hangzhou, 310022, China; Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou, 310022, China.
| | - Jing-Yuan Fang
- State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200001, China.
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22
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Extracellular Vesicle-Loaded Oncogenic lncRNA NEAT1 from Adipose-Derived Mesenchymal Stem Cells Confers Gemcitabine Resistance in Pancreatic Cancer via miR-491-5p/Snail/SOCS3 Axis. Stem Cells Int 2023; 2023:6510571. [PMID: 36762032 PMCID: PMC9902843 DOI: 10.1155/2023/6510571] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 12/07/2022] [Accepted: 12/22/2022] [Indexed: 02/01/2023] Open
Abstract
It is becoming increasingly evident that key mechanisms of mesenchymal stem cell (MSC) efficacy appear to associate with paracrine activities, and the delivery of cargos through extracellular vesicles (EVs) controls the mechanistic actions of MSCs. Thus, this study clarified a possible mechanism by which EV-encapsulated NEAT1 from adipose-derived mesenchymal stem cells (ADSCs) might mediate gemcitabine resistance in pancreatic cancer (PCa). Microarray profile suggested a differentially expressed lncRNA NEAT1 in PCa, and we determined its expression in PCa cells. NEAT1 was found to be upregulated in PCa. The binding affinity among NEAT1, miR-491-5p, and Snail was identified through bioinformatic analysis and experimental validation. NEAT1 competitively bound to miR-491-5p to elevate Snail expression and diminish SOCS3 expression. PCa cells were cocultured with EVs extracted from ADSCs, followed by assessment of malignant phenotypes, tumorigenesis, and gemcitabine resistance of PCa cells using gain- or loss-of-function experiments. ADSC-derived EVs carrying NEAT1 promoted PCa cell proliferation, migration, and gemcitabine resistance in vitro and enhanced tumorigenicity in vivo by inhibiting miR-491-5p and SOCS3 and upregulating Snail. Collectively, the findings from our study found a new potential strategy for gemcitabine resistance in PCa by illustrating the mechanistic insights of oncogenic ADSC-derived EVs-loaded NEAT1 via regulating the miR-491-5p/Snail/SOCS3 axis.
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23
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Zhang T, Wang H, Cai Z, Zhang S, Jiang C. RET rearrangement-positive pancreatic cancer has remarkable response to pralsetinib: a case report. Front Oncol 2023; 13:1078076. [PMID: 37139148 PMCID: PMC10149926 DOI: 10.3389/fonc.2023.1078076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 03/30/2023] [Indexed: 05/05/2023] Open
Abstract
Patients with metastatic pancreatic cancer have limited treatment options and a dismal prognosis. While RET fusion is rare (0.6%) in pancreatic cancer, the efficacy of RET-targeted treatment in patients with TRIM33-RET fusion has not been previously reported. Herein, we presented a case of a 68-year-old man with pancreatic cancer harboring TRIM33-RET fusion who responded remarkably to pralsetinib despite being intolerant to chemotherapy. To our knowledge, this is the first report on the clinical value of a single TRIM33-RET fusion in pancreatic cancer, which may benefit from the targeted therapy.
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Affiliation(s)
- Tongyi Zhang
- Department of General Surgery, Huadong Hospital, Fudan University, Shanghai, China
| | - Hongwei Wang
- Department of Hepato-Biliary-Pancreatic Surgery, Huadong Hospital, Fudan University, Shanghai, China
| | - Zhiwei Cai
- Department of Hepato-Biliary-Pancreatic Surgery, Huadong Hospital, Fudan University, Shanghai, China
| | - Siqi Zhang
- The Medical Department, 3D Medicines Inc., Shanghai, China
| | - Chongyi Jiang
- Department of General Surgery, Huadong Hospital, Fudan University, Shanghai, China
- Department of Hepato-Biliary-Pancreatic Surgery, Huadong Hospital, Fudan University, Shanghai, China
- *Correspondence: Chongyi Jiang,
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24
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Ji K, Dou W, Zhang N, Wen B, Zhong M, Zhang Q, Xu S, Zhou J, Liu J. Retinoic acid receptor gamma is required for proliferation of pancreatic cancer cells. Cell Biol Int 2023; 47:144-155. [PMID: 36183362 DOI: 10.1002/cbin.11917] [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: 08/05/2022] [Revised: 09/06/2022] [Accepted: 09/13/2022] [Indexed: 01/19/2023]
Abstract
Despite the expectation that retinoic acid receptor could be the potential therapeutic targets for pancreatic cancers, there has been the lack of information about the role and the impact of retinoic acid receptor gamma (RARγ, RARG) on pancreatic cancer, unlike other two RARs. Herein, we applied TCGA and GEO database to show that the expression and prognosis of RARG is closely related to pancreatic cancer, which demonstrates that RARG is commonly overexpressed in human pancreatic cancer and is an independent diagnostic marker predicting the poor prognosis of pancreatic cancer patients. In addition, we demonstrated that the reduction in the expression of RARG in human pancreatic cancer cells dramatically suppress their proliferation and tumor growth in vivo, partially attributable to the downregulation of tumor-supporting biological processes such as cell proliferation, antiapoptosis and metabolism and the decreased expression of various oncogenes like MYC and STAT3. Mechanistically, RARG binds on the promoters of MYC, STAT3, and SLC2A1 which is distinguished from well-known conventional Retinotic acid response elements (RAREs) and that the binding is likely to be responsible for the epigenetic activation in the level of chromatin, assessed by the measurement of deposition of the gene activation marker histone H3 K27 acetylation (H3K27ac) using ChIP-qPCR. In this study, we reveal that RARG plays important role in the tumorigenesis of pancreatic cancer and represents new therapeutic targets for human pancreatic cancer.
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Affiliation(s)
- Kaiyuan Ji
- Guangzhou Key Laboratory of Maternal-Fetal Medicine, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.,Medical Research Center, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Wenlong Dou
- Guangzhou Key Laboratory of Maternal-Fetal Medicine, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.,School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
| | - Ningfang Zhang
- Medical Research Center, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Bolun Wen
- Guangzhou Key Laboratory of Maternal-Fetal Medicine, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Mingyan Zhong
- School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
| | - Qianbing Zhang
- School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
| | - Shuxiang Xu
- School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
| | - Jianlong Zhou
- Department of Oncology, Guangxi International Zhuang Medicine Hospital, Nanning, Guangxi, China
| | - Jingfeng Liu
- School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.,Department of Hematology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China.,Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, Guangdong, China
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25
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Conde D, Rey C, Pardo M, Recaman A, Sabogal Olarte JC. Hepatic artery lymph node relevance in periampullary tumors: A retrospective analysis of survival outcomes. Front Surg 2022; 9:963855. [PMID: 36561573 PMCID: PMC9763566 DOI: 10.3389/fsurg.2022.963855] [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: 06/08/2022] [Accepted: 11/18/2022] [Indexed: 12/12/2022] Open
Abstract
Background The Periampullary area comprehends a heterogeneous and complex structure with different histological tissues. Surgical standards include the peripancreatic regional lymphadenectomy, and during pancreatoduodenectomy (PD) the hepatic artery lymph node HALN(8a) is dissected. We aimed to describe the prognostic significance of the HALN(8a) lymph node metastasis in terms of disease-free survival (DFS) and overall survival (OS) in a specific cohort of patients in limited economic and social conditions. Methods A retrospective study was conducted based on a prospective database from the HPB department of patients who underwent pancreaticoduodenectomy (PD) due to periampullary tumors during 2014-2021. Overall survival (OS) and disease-free survival (DFS) were estimated to be associated with positive HALN(8a) using Kaplan-Meier analysis. Log Rank test and Cox proportional hazards regression analysis was used. Results 111 patients were included, 55,4% female. The most frequent pathology was ductal adenocarcinoma (60.3%). The positive rate of the HALN(8a) node was 21.62%. The Median OS time was 25.5 months, and the median DFS time was 13,8 months. Positive HLAN(8a) node, the cutoff of lymph node ratio resection (LNRR), and vascular invasion showed a strong association with OS. (CoxRegression p = 0.03 HR 0.5, p 0.003 HR = 1.8, p = 0.02 HR 0.4 CI 95%). In terms of DFS, lymph node ratio cutoff, tumoral size, and vascular invasion showed a statistically significant association with the outcome (p = 0.008, HR = 1.5; p = 0.04 HR = 2.1; p = 0.02 HR = 0.4 CI 95%). Conclusion In this series of PD, OS was reduced in patients with HALN(8a) compromise in patients with pancreatic cancer, however without statistical significance in DFS. In multivariate analysis, lymph node status remains an independent predictor of OS and DFS. Further studies are needed.
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Affiliation(s)
- Danny Conde
- Department of Hepatobiliary and Pancreatic Surgery, Hospital Universitario Mayor Méderi, Bogotá, Colombia
| | - Carlos Rey
- School of Medicine, Universidad el Rosario, Bogotá, Colombia
| | - Manuel Pardo
- School of Medicine, Universidad el Rosario, Bogotá, Colombia
| | - Andrea Recaman
- School of Medicine, Universidad el Rosario, Bogotá, Colombia
| | - Juan Carlos Sabogal Olarte
- Chief and Chairman of Hepatobiliary and Pancreatic Surgery Department, Hospital Universitario Mayor Méderi, Bogotá, Colombia
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26
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Cui J, Jiao F, Li Q, Wang Z, Fu D, Liang J, Liang H, Xia T, Zhang T, Zhang Y, Dai G, Zhang Z, Wang J, Bai Y, Bai Y, Bi F, Chen D, Cao D, Chen J, Fang W, Gao Y, Guo J, Hao J, Hua H, Huang X, Liu W, Liu X, Li D, Li J, Li E, Li Z, Pan H, Shen L, Sun Y, Tao M, Wang C, Wang F, Xiong J, Zhang T, Zhang X, Zhan X, Zheng L, Ren G, Zhang T, Zhou J, Ma Q, Qin S, Hao C, Wang L. Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of pancreatic cancer. JOURNAL OF THE NATIONAL CANCER CENTER 2022; 2:205-215. [PMID: 39036552 PMCID: PMC11256594 DOI: 10.1016/j.jncc.2022.08.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 07/30/2022] [Accepted: 08/18/2022] [Indexed: 11/25/2022] Open
Abstract
Pancreatic cancer is one of the leading causes of cancer-related mortality in both developed and developing countries. The incidence of pancreatic cancer in China accounts for about a quater of the global incidence, and the epidemiological characteristics and therapeutic strategies differ due to social, economic, cultural, environmental, and public health factors. Non-domestic guidelines do not reflect the clinicopathologic characteristics and treatment patterns of Chinese patients. Thus, in 2018, the Chinese Society of Clinical Oncology (CSCO) organized a panel of senior experts from all sub-specialties within the field of pancreatic oncology to compile the Chinese guidelines for the diagnosis and treatment of pancreatic cancer. The guidelines were made based on both the Western and Eastern clinical evidence and updated every one or two years. The experts made consensus judgments and classified evidence-based recommendations into various grades according to the regional differences, the accessibility of diagnostic and treatment resources, and health economic indexes in China. Here we present the latest version of the guidelines, which covers the diagnosis, treatment, and follow-up of pancreatic cancer. The guidelines might standardize the diagnosis and treatment of pancreatic cancer in China and will encourage oncologists to design and conduct more clinical trials about pancreatic cancer.
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Affiliation(s)
- Jiujie Cui
- Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Feng Jiao
- Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Qi Li
- Department of Medical Oncology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zheng Wang
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Deliang Fu
- Department of Pancreatic Surgery, Huashan Hospital, Pancreatic Disease Institute, Fudan University, Shanghai, China
| | - Jun Liang
- Department of Oncology, Peking University International Hospital, Beijing, China
| | - Houjie Liang
- Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Tingyi Xia
- Beijing Huaxia Jingfang Cancer Radiotherapy Center, Former Air Force General Hospital and PLA General Hospital, Beijing, China
| | - Tao Zhang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yang Zhang
- Department of Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Guanghai Dai
- Department of Oncology, Chinese PLA General Hospital, Beijing, China
| | - Zhihong Zhang
- Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jian Wang
- Department of Imaging, Changzheng Hospital, Naval Military Medical University, Shanghai, China
| | - Yongrui Bai
- Department of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yuxian Bai
- Oncology Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin, China
| | - Feng Bi
- Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Donghui Chen
- Department of Medical Oncology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Dan Cao
- Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Jie Chen
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weijia Fang
- Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yong Gao
- Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Jianwei Guo
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Jihui Hao
- Department of Pancreatic Cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Haiqing Hua
- Department of Medical Oncology, Eastern Theater Command General Hospital, Qinhuai Medical District, Nanjing, China
| | - Xinyu Huang
- Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Wenchao Liu
- Department of Clinical Oncology, Xijing Hospital, Air Force Medical University, Xian, China
| | - Xiufeng Liu
- Department of Medical Oncology, Eastern Theater Command General Hospital, Qinhuai Medical District, Nanjing, China
| | - Da Li
- Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine, Hangzhou, China
| | - Ji Li
- Department of Pancreatic Surgery, Huashan Hospital, Pancreatic Disease Institute, Fudan University, Shanghai, China
| | - Enxiao Li
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zhiwei Li
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Hongming Pan
- Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine, Hangzhou, China
| | - Lin Shen
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China
| | - Yongwei Sun
- Department of Biliary-Pancreatic Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China
| | - Min Tao
- Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Chengfeng Wang
- State Key Lab of Molecular Oncology & 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, China
| | - Fenghua Wang
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jianping Xiong
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Taiping Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xuebin Zhang
- Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Xianbao Zhan
- Department of Medical Oncology, Changhai Hospital of Shanghai, Navy Medical University, Shanghai, China
| | - Leizhen Zheng
- Department of Oncology, Xin Hua Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Gang Ren
- Peking University Shougang Hospital, Beijing, China
| | - Tingting Zhang
- Oncology Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin, China
| | - Jun Zhou
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China
| | - Qingyong Ma
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Shukui Qin
- Department of Medical Oncology, Eastern Theater Command General Hospital, Qinhuai Medical District, Nanjing, China
| | - Chunyi Hao
- Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital, Beijing, China
| | - Liwei Wang
- Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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27
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Al-Awsi GRL, Jasim SA, Fakri Mustafa Y, Alhachami FR, Ziyadullaev S, Kandeel M, Abulkassim R, Sivaraman R, M Hameed N, Mireya Romero Parra R, Karampoor S, Mirzaei R. The role of miRNA-128 in the development and progression of gastrointestinal and urogenital cancer. Future Oncol 2022; 18:4209-4231. [PMID: 36519554 DOI: 10.2217/fon-2022-0574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Increasing data have shown the significance of various miRNAs in malignancy. In this regard, parallel to its biological role in normal tissues, miRNA-128 (miR-128) has been found to play an essential immunomodulatory function in the process of cancer initiation and development. The occurrence of the aberrant expression of miR-128 in tumors and the unique properties of miRNAs raise the prospect of their use as biomarkers and the next generation of molecular anticancer therapies. The function of miR-128 in malignancies such as breast, prostate, colorectal, gastric, pancreatic, esophageal, cervical, ovarian and bladder cancers and hepatocellular carcinoma is discussed in this review. Finally, the effect of exosomal miR-128 on cancer resistance to therapeutics and cancer immunotherapy in certain malignancies is highlighted.
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Affiliation(s)
| | - Saade Abdalkareem Jasim
- Department of Medical Laboratory Techniques, Al-maarif University College, Al-Anbar-Ramadi, Iraq
| | - Yasser Fakri Mustafa
- Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul, 41001, Iraq
| | - Firas Rahi Alhachami
- Department of Radiology, College of Health & Medical Technololgy, Al-Ayen University, Thi-Qar, Iraq
| | - Shukhrat Ziyadullaev
- No. 1 Department of Internal Diseases, Vice-rector for Scientific Affairs & Innovations, Samarkand State Medical University, Amir Temur Street 18, Samarkand, Uzbekistan
| | - Mahmoud Kandeel
- Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-Hofuf, Al-Ahsa, 31982, Saudi Arabia.,Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelshikh University, Kafrelshikh, 33516, Egypt
| | | | - R Sivaraman
- Department of Mathematics, Dwaraka Doss Goverdhan Doss Vaishnav College, Arumbakkam, University of Madras, Chennai, India
| | - Noora M Hameed
- Anesthesia Techniques, Al-Nisour University College, Iraq
| | | | - Sajad Karampoor
- Gastrointestinal & Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Rasoul Mirzaei
- Department of Medical Biotechnology, Venom & Biotherapeutics Molecules Lab, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
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28
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Xu Z, Yu W, Li L, Wang G. Identification of pyroptosis-related gene signature for predicting prognosis of patients with pancreatic cancer using bioinformatics. Medicine (Baltimore) 2022; 101:e31043. [PMID: 36253973 PMCID: PMC9575720 DOI: 10.1097/md.0000000000031043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Pancreatic cancer, a common digestive system malignancy, is dubbed the "king of cancers". The role of pyrophosis-related genes (PRGs) in pancreatic cancer prognosis is yet unknown. In pancreatic cancer and normal tissue, we discovered 9 PRGs that are expressed differently in pancreatic cancer and healthy tissue. Based on the differential expression of PRGs, 2 clusters of pancreatic cancer cases could be identified. The 2 groups had significant disparities in total survival time. The prognostic model of a 5-PRGs signature was created using least absolute shrinkage and selection operator (LASSO) method. The median risk score was used to split pancreatic cancer patients in The Cancer Genome Atlas (TCGA) cohort into 2 groups: low risk and high risk. Patients classified as low-risk had significantly higher survival rates than those classified as high-risk (P < .01). The same results were obtained by validating them against the Gene Expression Omnibus database (P = .030). Cox regression statistical analysis showed that risk score was an independent predictor of overall survival in pancreatic cancer patients. Functional enrichment analysis revealed that apoptosis, cell proliferation, and cell cycle-related biological processes and signaling pathways were enriched. Additionally, the immunological status of the high-risk group worsened. In conclusion, a novel pyroptosis-related gene signature can be used to predict pancreatic cancer patient prognosis.
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Affiliation(s)
- Zhongbo Xu
- Emergency Department, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China
| | - Wenyan Yu
- The Research Center for Differentiation and Development of Basic Theories of Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China
| | - Lin Li
- Emergency Department, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China
| | - Guojuan Wang
- Department of Oncology, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China
- *Correspondence: Guojuan Wang, Department of Oncology, Affiliated Hospital of Jiangxi University of Chinese Medicine, No.445, Bayi Avenue, Nanchang 330006, Jiangxi, China (e-mail: )
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Yu X, Zhang Q, Zhang S, He Y, Guo W. Single-cell sequencing and establishment of an 8-gene prognostic model for pancreatic cancer patients. Front Oncol 2022; 12:1000447. [PMID: 36237305 PMCID: PMC9552769 DOI: 10.3389/fonc.2022.1000447] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 09/05/2022] [Indexed: 11/15/2022] Open
Abstract
Background Single-cell sequencing (SCS) technologies enable analysis of gene structure and expression data at single-cell resolution. However, SCS analysis in pancreatic cancer remains largely unexplored. Methods We downloaded pancreatic cancer SCS data from different databases and applied appropriate dimensionality reduction algorithms. We identified 10 cell types and subsequently screened differentially expressed marker genes of these 10 cell types using FindAllMarkers analysis. Also, we evaluated the tumor immune microenvironment based on ESTIMATE and MCP-counter. Statistical enrichment was evaluated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. We used all candidate gene sets in KEGG database to perform gene set enrichment analysis. We used LASSO regression to reduce the number of genes in the pancreatic risk model by R package glmnet, followed by rtPCR to validate the expression of the signature genes in different pancreatic cancer cell lines. Results We identified 15 cell subpopulations by dimension reduction and data clustering. We divided the 15 subpopulations into 10 distinct cell types based on marker gene expression. Then, we performed functional enrichment analysis for the 352 marker genes in pancreatic cancer cells. Based on RNA expression data and prognostic information from TCGA and GEO datasets, we identified 42 prognosis-related genes, including 5 protective genes and 37 high-risk genes, which we used to identified two molecular subtypes. C1 subtype was associated with a better prognosis, whereas C2 subtype was associated with a worse prognosis. Moreover, chemokine and chemokine receptor genes were differentially expressed between C1 and C2 subtypes. Functional and pathway enrichment uncovered functional differences between C1 and C2 subtype. We identified eight genes that could serve as potential biomarkers for prognosis prediction in pancreatic cancer patients. These genes were used to establish an 8-gene pancreatic cancer prognostic model. Conclusions We established an 8-gene pancreatic cancer prognostic model. This model can meaningfully predict prognosis and treatment response in pancreatic cancer patients.
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Affiliation(s)
- Xiao Yu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Qiyao Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shuijun Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yuting He
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- *Correspondence: Wenzhi Guo, ; Yuting He,
| | - Wenzhi Guo
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- *Correspondence: Wenzhi Guo, ; Yuting He,
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Li R, Xiong G, Zhao J, Yang L. Targeting the alterations of ARID1A in pancreatic cancer: tumorigenesis, prediction of treatment, and prognostic value. Am J Transl Res 2022; 14:5952-5964. [PMID: 36247295 PMCID: PMC9556451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 08/01/2022] [Indexed: 06/16/2023]
Abstract
The chromatin remodeling gene AT-rich interactive domain 1A (ARID1A), encoding a subunit of the switch/sucrose non-fermentable (SWI/SNF) complex, is one of the most frequently mutated chromatin regulators across a broad spectrum of cancers. Most of the ARID1A alterations are inactivating, leading to the loss or reduced expression of the protein. Recently, ARID1A has been demonstrated as a tumor suppressor gene in pancreatic ductal adenocarcinoma (PDAC), as its inactive alterations attribute to carcinogenesis. Importantly, ARID1A alterations are revealed as predictive biomarkers for the selection of targeted therapy and immune checkpoint blockade (ICB) therapy. In PDAC, the application of ARID1A alterations in stratifying patients for precise treatment has also been widely explored in preclinical and early clinic studies with encouraging preliminary results. Furthermore, the prognostic value of ARID1A mutations in PDAC has been suggested by various studies. In this review, we focus on the functions of ARID1A alterations in PDAC, particularly their functions during carcinogenesis and their predictive value in treatment selection and prognosis, to provide a comprehensive overview on our current understanding of ARID1A alterations in PDAC.
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Affiliation(s)
- Ruichao Li
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, China
| | - Guangbing Xiong
- Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, China
| | - Jun Zhao
- School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, China
| | - Lin Yang
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, China
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Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects. Int J Mol Sci 2022; 23:ijms231710132. [PMID: 36077529 PMCID: PMC9456549 DOI: 10.3390/ijms231710132] [Citation(s) in RCA: 61] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 09/01/2022] [Accepted: 09/01/2022] [Indexed: 02/06/2023] Open
Abstract
Although pancreatic cancer (PC) was considered in the past an orphan cancer type due to its low incidence, it may become in the future one of the leading causes of cancer death. Pancreatic ductal adenocarcinoma (PDAC) is the most frequent type of PC, being a highly aggressive malignancy and having a 5-year survival rate of less than 10%. Non-modifiable (family history, age, genetic susceptibility) and modifiable (smoking, alcohol, acute and chronic pancreatitis, diabetes mellitus, intestinal microbiota) risk factors are involved in PC pathogenesis. Chronic inflammation induced by various factors plays crucial roles in PC development from initiation to metastasis. In multiple malignant conditions such as PC, cytokines, chemokines, and growth factors activate the class I phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) (PI3K/AKT/mTOR) signaling pathway, which plays key roles in cell growth, survival, proliferation, metabolism, and motility. Currently, mTOR, AKT, and PI3K inhibitors are used in clinical studies. Moreover, PI3K/mTOR dual inhibitors are being tested in vitro and in vivo with promising results for PC patients. The main aim of this review is to present PC incidence, risk factors, tumor microenvironment development, and PI3K/AKT/mTOR dysregulation and inhibitors used in clinical, in vivo, and in vitro studies.
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N6-methyladenosine-mediated CELF2 regulates CD44 alternative splicing affecting tumorigenesis via ERAD pathway in pancreatic cancer. Cell Biosci 2022; 12:125. [PMID: 35941702 PMCID: PMC9361702 DOI: 10.1186/s13578-022-00844-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Accepted: 07/07/2022] [Indexed: 11/10/2022] Open
Abstract
Background Alternative splicing (AS) of genes has been found to affect gene stability, and its abnormal regulation can lead to tumorigenesis. CELF2 is a vital splicing factor to participate in mRNA alternative splicing. Its downregulation has been confirmed to promote the occurrence and development of pancreatic cancer (PC). However, the regulatory role and mechanisms in PC has not been elucidated. Results CELF2 was downregulated in PC tissues, which affected tumor TNM stage and tumor size, and low expression of CELF2 indicated a poor prognosis of PC. In vivo and in vitro experiments showed that abnormal expression of CELF2 affected the stemness, apoptosis, and proliferation of PC cells. Furthmore, we also found that CELF2 was targeted by ALKBH5 for m6A modification, leading to CELF2 degradation by YTHDF2. Bioinformatic analysis of AS model based on the TCGA database indicated that CELF2 could target CD44 to form different spliceosomes, thereby affecting the biological behavior of PC cells. The conversion of CD44s to CD44V is the key to tumorigenesis. Transcriptomic analysis was conducted to reveal the mechanism of CELF2-mediated CD44 AS in PC. We found that CELF2-mediated splicing of CD44 led to changes in the level of endoplasmic reticulum stress, further regulating the endoplasmic reticulum-associated degradation (ERAD) signaling pathway, thereby affecting apoptosis and cell stemness. In addition, ERAD signaling pathway inhibitor, EerI, could effectively reverse the effect of CD44 on tumors. Conclusions This study indicates that N6-methyladenosine-mediated CELF2 promotes AS of CD44, affecting the ERAD pathway and regulating the biological behavior of PC cells. CELF2 is expected to be a new target for targeted-drug development. Supplementary Information The online version contains supplementary material available at 10.1186/s13578-022-00844-0.
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Yu Q, Xiu Z, Jian Y, Zhou J, Chen X, Chen X, Chen C, Chen H, Yang S, Yin L, Zeng W. microRNA-497 prevents pancreatic cancer stem cell gemcitabine resistance, migration, and invasion by directly targeting nuclear factor kappa B 1. Aging (Albany NY) 2022; 14:5908-5924. [PMID: 35896012 PMCID: PMC9365558 DOI: 10.18632/aging.204193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 05/23/2022] [Indexed: 11/25/2022]
Abstract
Objectives: Cancer stem cells (CSCs) comprise a small population of cells in cancerous tumors and play a critical role in tumor resistance to chemotherapy. miRNAs have been reported to enhance the sensitivity of pancreatic cancer to chemotherapy. However, the underlying molecular mechanism requires better understanding. Methods: Cell viability and proliferation were examined with CCK8 assays. Quantitative real-time polymerase chain reaction was executed to assess mRNA expression. StarBase database was used to select the target genes of miRNA, which were further affirmed by dual luciferase assay. Transwell assay was used to analyze cell invasion and migration. Results: We proved that miR-497 could be obviously downregulated in pancreatic cancer tissues and CSCs from Aspc-1 and Bxpc-3 cells. In addition, inhibition of miR-497 evidently accelerated pancreatic CSC gemcitabine resistance, migration and invasion. Moreover, we revealed that nuclear factor kappa B 1 (NFκB1) was prominently upregulated in pancreatic cancer tissues and pancreatic CSCs, and NFκB1 was also identified as a direct target of miR-497. Furthermore, we demonstrated that overexpression of NFκB1 could also notably promote the viability, migration, and invasion of gemcitabine-treated pancreatic CSCs, but this effect could be partially abolished by miR-497 overexpression. Conclusions: Those findings suggest that miR-497 overexpression could suppress gemcitabine resistance and the metastasis of pancreatic CSCs and non-CSCs by directly targeting NFκB1.
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Affiliation(s)
- Qiangfeng Yu
- The Second Department of General Surgery, Zhuhai People's Hospital, Zhuhai 51900, Guangdong, China
| | - Zhe Xiu
- Department of Hepatobiliary Surgery, The Second Hospital of Longyan, Longyan 364000, Fujian, China
| | - Yizeng Jian
- Department of Hepatobiliary Surgery, The Second Hospital of Longyan, Longyan 364000, Fujian, China
| | - Jianyin Zhou
- Department of Hepatobiliary and Pancreatic Surgery, Zhongshan Hospital, Xiamen University, Xiamen 361000, Fujian, China
| | - Xiaopeng Chen
- Department of Hepatobiliary Surgery, The Second Hospital of Longyan, Longyan 364000, Fujian, China
| | - Xiang Chen
- The Third Department of Surgery, The Second Hospital of Longyan, Longyan 364000, Fujian, China
| | - Chunxiang Chen
- Department of Science and Education, The Second Hospital of Longyan, Longyan 364000, Fujian, China
| | - Hongbao Chen
- Department of Pathology, The Second Hospital of Longyan, Longyan 364000, Fujian, China
| | - Sijia Yang
- The Second Department of General Surgery, Zhuhai People's Hospital, Zhuhai 51900, Guangdong, China
| | - Libo Yin
- The First People's Hospital of Wenling, The Affiliated Wenling Hospital of Wenzhou Medical University, Wenzhou 317500, Zhejiang, China
| | - Wenlong Zeng
- Department of Hepatobiliary Surgery, The Second Hospital of Longyan, Longyan 364000, Fujian, China
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Zeng Y, Zhang H, Zhu M, Pu Q, Li J, Hu X. β-Hydroxyisovaleryl-Shikonin Exerts an Antitumor Effect on Pancreatic Cancer Through the PI3K/AKT Signaling Pathway. Front Oncol 2022; 12:904258. [PMID: 35860565 PMCID: PMC9293047 DOI: 10.3389/fonc.2022.904258] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 05/02/2022] [Indexed: 12/17/2022] Open
Abstract
Pancreatic cancer (PC) is marked with a low survival rate and lack of recognized effective treatment strategy. We investigated the antitumor effect of β-hydroxyisovaleryl-shikonin (β-HIVS) on PC and the associated working mechanism. Cell toxicity was determined using Cell Counting Kit-8 (CCK-8) assay. Acridine Orange/Ethidium Bromide (AO/EB) double-fluorescent staining assay accompanied by flow cytometry was utilized to estimate cell apoptosis. Cell cycle, reactive oxygen species (ROS), and mitochondrial membrane potential were all evaluated using flow cytometry. Transwell and wound healing assays were performed to evaluate cell migration and invasion. Protein expression was analyzed by Western blots. A xenograft mouse model was employed to determine the antitumor effect of β-HIVS in vivo. PC cell viability gradually decreased with increasing β-HIVS while apoptosis was enhanced together with cell-cycle blockage in the G0–G1 phases. β-HIVS induced mitochondrial dysfunction, ROS production, and DNA damage and inhibited the invasive and migratory ability of PC cells. We further confirmed the suppression of EMT and PI3K/AKT pathways as underlying mechanisms. The mouse model treated with the increasing dose of β-HIVS displayed decreased tumor growth rate, along with increased apoptosis. Thus, β-HIVS exerts antitumor effects on PC through inducing apoptosis, ROS production, decreasing mitochondrial membrane potential, and suppressing signal pathways, such as PI3K/AKT. In summary, β-HIVS might be a promising strategy for PC treatment.
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Tian N, Wu D, Zhu L, Zeng M, Li J, Wang X. A predictive model for recurrence after upfront surgery in patients with resectable pancreatic ductal adenocarcinoma (PDAC) by using preoperative clinical data and CT characteristics. BMC Med Imaging 2022; 22:116. [PMID: 35786426 PMCID: PMC9252003 DOI: 10.1186/s12880-022-00823-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 05/10/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND The overall survival for patients with resectable PDAC following curative surgical resection hasn't been improved significantly, as a considerable proportion of patients develop recurrence within a year. The purpose of this study was to develop and validate a predictive model to assess recurrence risk in patients with PDAC after upfront surgery by using preoperative clinical data and CT characteristics. METHODS The predictive model was developed based on a retrospective set of 141 pancreatic cancer patients after surgery. A separate set of 77 patients was used to validate model. Between January 2017 and December 2019, all patients underwent multidetector pancreatic CT and upfront surgery. Univariable and multivariate Cox regression was used to determine the risk factors related to recurrence and then establish a nomogram to estimate the 1-year recurrence probability. The Harrell C-index was employed in evaluating the discrimination and calibration of the model. RESULTS A total of 218 patients in this retrospective cohort. A recurrence model in nomogram form was developed with predictors including tumor size (hazard ratio [HR], 1.277; 95% CI 1.098, 1.495; P = 0.002), tumor density in the portal vein phase (HR, 0.598; 95% CI 0.424, 0.844; P = 0.003), peripancreatic infiltration (HR, 4.151; 95% CI 2.077, 8.298; P < 0.001), suspicious metastatic lymph node (HR, 2.561; 95% CI 1.653, 3.967; P < 0.001), Neutrophils/Lymphocytes ratio (HR, 1.111; 95% CI 1.016, 1.215; P = 0.020). The predictive nomogram had good discrimination capability with these predictors with an area under curve at 1 year of 0.84 (95%CI 0.77, 0.91) in the development set and 0.82 (95% CI 0.72, 0.92) and 0.84 (95% CI 0.74, 0.94) in the validation set for two radiologists reading respectively. CONCLUSIONS The model developed based on preoperative clinical data and CT characteristics of resectable pancreatic ductal adenocarcinoma patients, which can helpfully estimate the recurrence-free survival. It may be a useful tool for clinician to select optimal candidates for upfront surgery or neoadjuvant therapy.
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Affiliation(s)
- Ningzi Tian
- Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Dong Wu
- Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Lei Zhu
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Mengsu Zeng
- Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Jianke Li
- Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Xiaolin Wang
- Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
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Wu X, Wang J, Liang Q, Tong R, Huang J, Yang X, Xu Y, Wang W, Sun M, Shi J. Recent progress on FAK inhibitors with dual targeting capabilities for cancer treatment. Biomed Pharmacother 2022; 151:113116. [PMID: 35598365 DOI: 10.1016/j.biopha.2022.113116] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 04/30/2022] [Accepted: 05/10/2022] [Indexed: 02/08/2023] Open
Abstract
Focal adhesion kinase (FAK, also known as PTK2) is a tyrosine kinase that regulates integrin and growth factor signaling pathways and is involved in the migration, proliferation and survival of cancer cells. FAK is a promising target for cancer treatment. Many small molecule FAK inhibitors have been identified and proven in both preclinical and clinical studies to be effective inhibitors of tumor growth and metastasis. There are many signaling pathways, such as those involving FAK, Src, AKT, MAPK, PI3K, and EGFR/HER-2, that provide survival signals in cancer cells. Dual inhibitors that simultaneously block FAK and another factor can significantly improve efficacy and overcome some of the shortcomings of single-target inhibitors, including drug resistance. In this review, the antitumor mechanisms and research status of dual inhibitors of FAK and other targets, such as Pyk2, IGF-IR, ALK, VEGFR-3, JAK2, EGFR, S6K1, and HDAC2, are summarized, providing new ideas for the development of effective FAK dual-target preparations.
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Affiliation(s)
- Xianbo Wu
- School of Sports Medicine and Health, Chengdu Sport University, Chengdu, Sichuan 610041, China
| | - Jie Wang
- Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550002, China
| | - Qi Liang
- College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, 610031, China
| | - Rongsheng Tong
- Personalized Drug Therapy Key Laboratory of Sichuan Province, Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China
| | - Jianli Huang
- Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550002, China
| | - Xinwei Yang
- School of Sports Medicine and Health, Chengdu Sport University, Chengdu, Sichuan 610041, China
| | - Yihua Xu
- Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China
| | - Wenjing Wang
- State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
| | - Minghan Sun
- Central of Reproductive Medicine, Department of Obstetrics and Gynecology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
| | - Jianyou Shi
- Personalized Drug Therapy Key Laboratory of Sichuan Province, Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China.
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Gao LJ, Li JL, Yang RR, He ZM, Yan M, Cao X, Cao JM. Biological Characterization and Clinical Value of OAS Gene Family in Pancreatic Cancer. Front Oncol 2022; 12:884334. [PMID: 35719943 PMCID: PMC9205247 DOI: 10.3389/fonc.2022.884334] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Accepted: 04/25/2022] [Indexed: 12/20/2022] Open
Abstract
Background OAS gene family plays an important role in antiviral process, but its role in pancreatic cancer has not yet been studied. Methods We analyzed the expression, prognostic value and biological function of the OAS gene family in human pancreatic cancer through comprehensive bioinformatic analysis and cellular level validation. Results OAS family was highly expressed in pancreatic cancer, and this high expression significantly affected the clinical stage and prognosis of the tumor. OAS gene family was closely related to the immune infiltration of pancreatic cancer, especially neutrophils and dendritic cells, and many immune-related factors and pathways are enriched in the tumor, such as type I interferon signaling pathway and NOD-like receptor signaling pathway. Conclusion Taken together, high expression of OAS family is closely related to poor prognosis of pancreatic cancer. OAS gene family may serve as the biomarker and even therapeutic target of pancreatic cancer.
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Affiliation(s)
- Li-Juan Gao
- Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China.,Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Jia-Lei Li
- Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China.,Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Rui-Rui Yang
- Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China.,Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Zhong-Mei He
- Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China.,Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Min Yan
- Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China.,Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Xia Cao
- Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China.,Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Ji-Min Cao
- Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China.,Department of Physiology, Shanxi Medical University, Taiyuan, China
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Zheng S, Liu D, Wang F, Jin Y, Zhao S, Sun S, Wang S. ABCA12 Promotes Proliferation and Migration and Inhibits Apoptosis of Pancreatic Cancer Cells Through the AKT Signaling Pathway. Front Genet 2022; 13:906326. [PMID: 35783291 PMCID: PMC9243331 DOI: 10.3389/fgene.2022.906326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 05/18/2022] [Indexed: 11/17/2022] Open
Abstract
Background: As a malignant tumor, pancreatic cancer is difficult to detect in its early stage. Pancreatic cancer progresses rapidly and has a short survival time. Most cases have metastasized to distant organs before diagnosis. The mechanism of induction of pancreatic cancer is not fully understood. Methods: In this study, bioinformatics predicted ATP binding cassette subfamily A member 12 (ABCA12) expression in pancreatic tissues and performed survival analysis, risk assessment, and enrichment analysis. The expression of ABCA12 in 30 pairs of clinical samples was detected by immunohistochemistry and we analyzed its correlation with clinical information. Both reverse transcription polymerase chain reaction (RT–PCR) and western blot analysis were used to detect mRNA and protein expression in cell lines. Two different siRNAs and SW1990 cell line were used to construct pancreatic cancer cell models with ABCA12 knockdown. Cell viability was evaluated by cell counting kit-8 (CCK-8) and EdU proliferation assays. Wound healing assays and Transwell assays were used to measure the ability of cell migration and invasion. Flow cytometry was used to investigate the effect of ABCA12 on the proliferation cycle and apoptosis of pancreatic cancer. Western blot analysis detected changes in apoptosis, migration, and other pathway proteins in SW1990 cells after transfection. Results:ABCA12 is highly expressed in pancreatic cancer tissues and cells. After ABCA12 was knocked down, the proliferation, invasion, and migration of SW1990 cells were significantly reduced, and apoptosis was increased. The changes in pathway proteins suggested that ABCA12 may regulate the progression of pancreatic cancer through the AKT pathway. Conclusion: We found that ABCA12 is differentially expressed in pancreatic tissues and cells. ABCA12 can also affect the biological behavior of pancreatic cancer cells effectively, which may serve as a new target for pancreatic cancer diagnosis and treatment.
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Affiliation(s)
- Songyuan Zheng
- Department of Endoscopy Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Dongyan Liu
- Department of Gastroenterology and Medical Research Center, Liaoning Key Laboratory of Research and Application of Animal Models for Environmental and Metabolic Diseases, Shengjing Hospital of China Medical University, Shenyang, China
| | - Feifei Wang
- Department of Endoscopy Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Youyan Jin
- Department of Endoscopy Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Siqiao Zhao
- Department of Endoscopy Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Siyu Sun
- Department of Endoscopy Center, Shengjing Hospital of China Medical University, Shenyang, China
- *Correspondence: Siyu Sun, ; Sheng Wang,
| | - Sheng Wang
- Department of Endoscopy Center, Shengjing Hospital of China Medical University, Shenyang, China
- *Correspondence: Siyu Sun, ; Sheng Wang,
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Huang WL, Wu SF, Huang X, Zhou S. Integrated Analysis of ECT2 and COL17A1 as Potential Biomarkers for Pancreatic Cancer. DISEASE MARKERS 2022; 2022:9453549. [PMID: 35722628 PMCID: PMC9200569 DOI: 10.1155/2022/9453549] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 05/25/2022] [Indexed: 11/30/2022]
Abstract
Background Pancreatic cancer (PC) is a malignant tumor of the digestive tract. It presents with atypical clinical symptoms and lacks specific diagnostic indicators. This study is aimed at exploring the potential biomarkers of PC. Methods TCGA database pancreatic cancer dataset was normalized and used to identify differentially expressed genes (DEGs). Survival, independent prognostic, and clinical correlation analyses were performed on DEGs to screen for key genes. DNA methylation, mutation, and copy number variation (CNV) analyses were used to analyze genetic variants in key genes. GSEA was performed to explore the functional enrichment of the key genes. Based on the expression of key genes, construction of a competing endogenous RNA (ceRNA) network, analysis of the tumor microenvironment (TME), and prediction of chemotherapeutic drug sensitivity were performed. Furthermore, the GEO database was used to validate the reliability of key genes. Results Two key genes (ECT2 and COL17A1) were identified, which were highly expressed in PC. The mRNA expression of ECT2 and COL17A1 was associated with DNA methylation and CNV. The cell cycle, proteasome, and pathways in cancer were enriched in the high-COL17A1 and ECT2 groups. The TME results showed that immune scores were decreased in the high-ECT2 group. CeRNA network results showed that there were eleven miRNAs were involved in the regulation of ECT2 and COL17A1. Moreover, pRRophetic analysis showed that 20 chemotherapeutic drugs were associated with ECT2 and COL17A1 expression. Conclusions Collectively, ECT2 and COL17A1 may be potential biomarkers for PC, providing a new direction for clinical diagnosis and treatment.
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Affiliation(s)
- Wen-liang Huang
- MRI Room, The Second Affiliated Hospital of Luohe Medical College, Luohe, China
| | - Shu-fen Wu
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Luohe Medical College, Luohe, China
| | - Xiao Huang
- Department of Clinical Laboratory, Zhengzhou University First Affiliated Hospital, Zhengzhou, China
| | - Shan Zhou
- MRI Room, The Second Affiliated Hospital of Luohe Medical College, Luohe, China
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Chen J, Chen H, Zhang T, Yin X, Man J, Yang X, Lu M. Burden of pancreatic cancer along with attributable risk factors in China from 1990 to 2019, and projections until 2030. Pancreatology 2022; 22:608-618. [PMID: 35513974 DOI: 10.1016/j.pan.2022.04.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 03/02/2022] [Accepted: 04/25/2022] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Understanding epidemiology trends and patterns of pancreatic cancer in China from 1990 to 2019 and predicting the burden to 2030 will provide foundations for future policies development. METHODS We collected incidence, mortality, and disability-adjusted life-years (DALYs) data of pancreatic cancer in China from 1990 to 2019 based on the Global Burden of Disease Study 2019. We calculated the estimated annual percentage change (EAPC) to depict the trends of pancreatic cancer burden and predicted the incidence and mortality in the next decade by using a Bayesian age-period-cohort analysis. RESULTS The number of incident cases sharply increased from 26.77 thousand in 1990 to 114.96 thousand in 2019, the age-standardized incidence rate (ASIR) nearly doubled from 3.17 per 100,000 in 1990 to 5.78 per 100,000 in 2019, with an EAPC of 2.32 (95% confidence interval [CI]: 2.12, 2.51). The mortality and DALYs presented a similar pattern with incidence. The dominant risk factor for pancreatic cancer was smoking, but the contribution of high body-mass index increased from 1990 to 2019. We projected that the incident cases and deaths of pancreatic cancer would increase to 218.79 thousand and 222.97 thousand, respectively, in 2030 with around 2 times growth. CONCLUSIONS During the past three decades, the incidence, mortality and DALYs of pancreatic cancer gradually increased in China, and the absolute number and rate of pancreatic cancer burden would continue to rise over the next decade. Comprehensive policies and strategies need to be implemented to reduce the incidence and mortality.
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Affiliation(s)
- Jiaqi Chen
- Department of Epidemiology and Health Statistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Hui Chen
- Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, China; Clinical Research Center of Shandong University, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Tongchao Zhang
- Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, China; Clinical Research Center of Shandong University, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xiaolin Yin
- Department of Epidemiology and Health Statistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Jinyu Man
- Department of Epidemiology and Health Statistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xiaorong Yang
- Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, China; Clinical Research Center of Shandong University, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China; Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
| | - Ming Lu
- Department of Epidemiology and Health Statistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China; Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, China; Clinical Research Center of Shandong University, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
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Solute Carrier Family 35 Member F2 Regulates Cisplatin Resistance and Promotes Malignant Progression of Pancreatic Cancer by Regulating RNA Binding Motif Protein 14. JOURNAL OF ONCOLOGY 2022; 2022:5091154. [PMID: 35669242 PMCID: PMC9166975 DOI: 10.1155/2022/5091154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/26/2022] [Accepted: 05/05/2022] [Indexed: 11/24/2022]
Abstract
We aimed to explore the role of Solute Carrier Family 35 Member F2 (SLC35F2) in pancreatic cancer (PCa) and to further study whether SLC35F2 regulates cisplatin resistance of PCa cells through the modulation of RNA binding motif protein 14 (RBM14) expression. SLC35F2 expression in 60 pairs of PCa tissues and adjacent ones was studied by RT-PCR analysis. Meanwhile, SLC35F2 expression levels in PCa cell lines were also evaluated by qPCR assay. In addition, SLC35F2 knockdown models were constructed in PCa cisplatin-resistant cells. Furthermore, we determined the interaction between SLC35F2 and RBM14 via luciferase assay. The findings of the present study demonstrated that SLC35F2 was significantly upregulated in PCa tissues. High level of SLC35F2 indicated higher incidence of metastasis and shorter survival rates. In vitro cell experiments revealed that knockdown of SLC35F2 suppressed cell invasion and metastasis capacity of cisplatin-resistant PCa cell lines PANC-1/DDP and CFPAC-1/DDP. It was also suggested that the key protein RBM14 in the SLC35F2 knockdown group was remarkably reduced. SLC35F2 can bind to RBM14 specifically. Overexpression of RBM14 partially reversed the effects of knockdown of SLC35F2 on the development of PCa. SLC35F2 expression in PCa tissues and cell lines is remarkably increased. In addition, it was also suggested that SLC35F2 may regulate cisplatin resistance of PCa cells through modulating RBM14 expression. In conclusion, it is conceivable from the study that SLC35F2 was remarkably upregulated in PCa and promoted the malignancy of PCa via regulating RBM14.
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Xu H, Yin L, Xu Q, Xiang J, Xu R. N6-methyladenosine methylation modification patterns reveal immune profiling in pancreatic adenocarcinoma. Cancer Cell Int 2022; 22:199. [PMID: 35606813 PMCID: PMC9125922 DOI: 10.1186/s12935-022-02614-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 05/06/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Several studies have revealed that N6-methyladenosine (m6A) regulation is involved in various biological processes and cancer progression. Nevertheless, the potential effects of m6A modifications in the tumor immune microenvironment (TIME) and on immune regulation in pancreatic adenocarcinoma (PAAD) remains unclear. METHODS A consensus clustering algorithm was used to identify different m6A modification patterns and construct an m6A-associated gene signature based on 23 m6A regulators in PAAD. The CIBERSORT and ssGSEA algorithms were used to estimate the components of the immune cells in each sample. The PCA algorithm was used to develop the m6Ascore system for the evaluation of m6A modification patterns in each sample. RESULTS Two m6A modification patterns with different biological properties and prognoses were identified in 176 PAAD patient samples. The features of TIME between the two patterns were similar, with two definite immune phenotypes: immune-inflamed and immune-excluded. Based on the m6A phenotype-associated signature genes, we constructed an m6Ascore system to investigate the m6A modification pattern of each sample, profile the dissection of physiological processes, immune infiltration, clinical prognosis, immunotherapy, and genetic variation. Patients with low m6Ascore scores had better clinical outcomes, enhanced immune infiltration, and lower expression of immunotherapeutic drug targets, such as CD274 and PDCD1LG2. Further research indicated that the m6Ascore and tumor mutation burden were significantly correlated, and patients with low m6Ascore had higher mutation rates in SMAD4 and TTN. Moreover, TNFRSF21 was significantly upregulated in PAAD tumor tissues and cell lines. Lower expression of TNFRSF21 had a prominent advantage in survival and was correlated with a low level of immune infiltration. PAAD samples with different TNFRSF21 expression levels showed significantly distinct sensitivities to chemotherapeutic agents. CONCLUSIONS This study revealed that m6A modification patterns could play an important role in the diversity and complexity of TIME, and the m6Ascore system could serve as an independent and powerful prognostic biomarker and is latently related to PAAD immunotherapies. Quantitative determination of m6A modification patterns in individual patients will be instrumental in mapping the TIME landscape and further optimizing precision immunotherapy.
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Affiliation(s)
- Hao Xu
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang China
| | - Lu Yin
- Department of Pathology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang China
| | - Qianhui Xu
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang China
| | - Jingjing Xiang
- Department of Pathology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang China
| | - Rujun Xu
- Department of Pathology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang China
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Yin MY, Xi LT, Liu L, Zhu JZ, Qian LJ, Xu CF. Pancreatic cancer incidence and mortality patterns in 2006-2015 and prediction of the epidemiological trend to 2025 in China. World J Clin Cases 2022; 10:4404-4413. [PMID: 35663052 PMCID: PMC9125275 DOI: 10.12998/wjcc.v10.i14.4404] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 09/09/2021] [Accepted: 03/25/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Due to dietary patterns, the aging population, and other high-risk factors, the occurrence of pancreatic cancer (PC) has been rapidly increasing in China. AIM To present the epidemiological trends of PC in China over the past decade and the estimated trend in 2025 and to compare the international differences in PC morbidity and mortality. METHODS This study used a series of nationally representative data from the National Central Cancer Registry of China (NCCR), the International Agency for Research on Cancer and the Institute for Health Metrics and Evaluation databases. Age-standardized data of the PC incidence and mortality from 2006 to 2015 in China were extracted from the NCCR database. Linear regression models were used to estimate the incidence and mortality rates of PC in 2025. RESULTS The age-standardized rates of PC in China increased from 3.65 per 100000 in 2006 to 4.31 per 100000 in 2015 and were estimated to reach up to 5.52 per 100000 in 2025. The mortality went from 3.35 per 100000 in 2006 to 3.78 per 100000 in 2015, estimated to reach up to 4.6 per 100000 in 2025. The number of new cases and deaths was low before 45 years and the peak age of onset was 85-89 years. The incidence and mortality rates in men were higher than those in women regardless of the region in China. In addition, the incidence and mortality rates in China were higher than the average level around the world. Likewise, disability-adjusted life years attributed to PC in China were 197.22 years per 100000, above the average level around the world. CONCLUSION This study presented an increasing trend of PC in China and differences in morbidity, mortality and disability-adjusted life years between Chinese and global populations. Efforts need to be made to decrease the PC incidence and improve patient outcomes.
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Affiliation(s)
- Min-Yue Yin
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Li-Ting Xi
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Lu Liu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Jin-Zhou Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Li-Juan Qian
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Chun-Fang Xu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
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Real-world study of surgical treatment of pancreatic cancer in China: Annual Report of China Pancreas Data Center (2016–2020). JOURNAL OF PANCREATOLOGY 2022. [DOI: 10.1097/jp9.0000000000000086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Jin Y, Wang W, Wang Q, Zhang Y, Zahid KR, Raza U, Gong Y. Alpha-1-antichymotrypsin as a novel biomarker for diagnosis, prognosis, and therapy prediction in human diseases. Cancer Cell Int 2022; 22:156. [PMID: 35439996 PMCID: PMC9019971 DOI: 10.1186/s12935-022-02572-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 04/06/2022] [Indexed: 12/15/2022] Open
Abstract
The glycoprotein alpha-1-antichymotrypsin (AACT), a serine protease inhibitor, is mainly synthesized in the liver and then secreted into the blood and is involved in the acute phase response, inflammation, and proteolysis. The dysregulation of AACT and its glycosylation levels are associated with tumor progression and recurrence, and could be used as a biomarker for tumor monitoring. In this review, we summarized the expression level, glycosylation modification, and biological characteristics of AACT during inflammation, neurodegenerative or other elderly diseases, and tumorigenesis, as well as, focused on the biological roles of AACT in cancer. The aberrant expression of AACT in cancer might be due to genetic alterations and/or immune by bioinformatics analysis. Moreover, AACT may serve as a diagnostic or prognostic biomarker or therapeutic target in tumors. Furthermore, we found that the expression of AACT was associated with the overall survival of patients with human cancers. Decreased AACT expression was associated with poor survival in patients with liver cancer, increased AACT expression was associated with shorter survival in patients with pancreatic cancer, and decreased AACT expression was associated with shorter survival in patients with early lung cancer. The review confirmed the key roles of AACT in tumorigenesis, suggesting that the glycoprotein AACT may serve as a biomarker for tumor diagnosis and prognosis, and could be a potential therapeutic target for human diseases.
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Affiliation(s)
- Yanxia Jin
- Hubei Key Laboratory of Edible Wild Plants Conservation and Utilization, College of Life Sciences, Hubei Normal University, No. 11 Cihu Road, Huangshi District, Huangshi, 435002, China
| | - Weidong Wang
- College of Life Sciences, Hubei Normal University, No. 11 Cihu Road, Huangshi District, Huangshi, 435002, China.
| | - Qiyun Wang
- Hubei Key Laboratory of Edible Wild Plants Conservation and Utilization, College of Life Sciences, Hubei Normal University, No. 11 Cihu Road, Huangshi District, Huangshi, 435002, China
| | - Yueyang Zhang
- Hubei Key Laboratory of Edible Wild Plants Conservation and Utilization, College of Life Sciences, Hubei Normal University, No. 11 Cihu Road, Huangshi District, Huangshi, 435002, China
| | - Kashif Rafiq Zahid
- Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Science and Oceanography, Carson International Cancer Center, Shenzhen University, Shenzhen, Guangdong, China
| | - Umar Raza
- Department of Biological Sciences, National University of Medical Sciences (NUMS), PWD Campus, Rawalpindi, Pakistan
| | - Yongsheng Gong
- Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, No.26 Daoqian Street, Suzhou, 215002, China.
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Li J, Liao G, Sun W, Sun J, Sheng T, Zhu K, von Deneen KM, Zhang Y. A 2.5D semantic segmentation of the pancreas using attention guided dual context embedded U-Net. Neurocomputing 2022. [DOI: 10.1016/j.neucom.2022.01.044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Qian X, Zong W, Ma L, Yang Z, Chen W, Yan J, Xu J. MM-associated circular RNA downregulates microRNA-19a through methylation to suppress proliferation of pancreatic adenocarcinoma cells. Bioengineered 2022; 13:9294-9300. [PMID: 35387554 PMCID: PMC9161914 DOI: 10.1080/21655979.2022.2051815] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 03/04/2022] [Accepted: 03/04/2022] [Indexed: 02/05/2023] Open
Abstract
Opposite roles of circular RNA MM-associated circular RNA (circ-MYBL2) have been observed in different malignancies, and its role in pancreatic adenocarcinoma (PA) is unknown. Our preliminary sequencing data revealed its inverse correlation with microRNA-19a (miR-19a). This study was performed to explore the role of circ-MYBL2 in PA and its crosstalk with miR-19a. The accumulation of circ-MYBL2 and miR-19a in PA was detected by RT-qPCR. Participation of circ-MYBL2 in the regulation of miR-19a and its RNA gene methylation was studied with an overexpression assay, followed by RT-qPCR and MSP analyses. The role of miR-19a and circ-MYBL2 in PA cell proliferation and movement was evaluated using the BrdU assay and the Transwell assay, respectively. Downregulation of circ-MYBL2 and upregulation of miR-19a were observed in PA. In PA cells, circ-MYBL2 decreased the accumulation of miR-19a but increased its RNA gene methylation. Overexpression of circ-MYBL2 decreased PA cell proliferation and movement, while overexpression of miR-19a showed an opposite effect. In addition, circ-MYBL2 suppressed the role of miR-19a in cell proliferation, migration, and invasion. In conclusion, circ-MYBL2 was downregulated in PA and it downregulated miR-19a through methylation to suppress PA cell proliferation.
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Affiliation(s)
- Xinye Qian
- Center of Hepatobiliary Pancreatic Disease, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing City, PR. China
| | - Wenru Zong
- Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai City, PR. China
| | - Liqing Ma
- Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai City, PR. China
| | - Zhoujing Yang
- Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai City, PR. China
| | - Wei Chen
- Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai City, PR. China
| | - Jun Yan
- Center of Hepatobiliary Pancreatic Disease, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing City, PR. China
| | - Jianghui Xu
- Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai City, PR. China
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Shao J, Liu Q, Shen J, Qian X, Yan J, Zhu Y, Qiu X, Lu C, Cen L, Tian M, Du J, Liu B. Advanced Pancreatic Cancer Patient Benefit From Personalized Neoantigen Nanovaccine Based Immunotherapy: A Case Report. Front Immunol 2022; 13:799026. [PMID: 35273594 PMCID: PMC8901600 DOI: 10.3389/fimmu.2022.799026] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 02/02/2022] [Indexed: 11/13/2022] Open
Abstract
Personal neoantigen vaccines are considered to be effective methods for inducing, amplifying and diversifying antitumor T cell responses. We recently conducted a clinical study that combined neoantigen nanovaccine with anti-PD-1 antibody. Here, we reported a case with a clear beneficial outcome from this treatment. We established a process that includes comprehensive identification of individual mutations, computational prediction of new epitopes, and design and manufacture of unique nanovaccines for this patient. Nanovaccine started after a relapse in third-line treatment. We assessed the patient's clinical outcome and circulating immune response. In this advanced pancreatic cancer patient, the OS associated with the vaccine treatment was 10.5 months. A peptide-specific T-cell response against 9 of the 12 vaccine peptides could be detected sequentially. Robust neoantigen-specific T cell responses were also detected by IFN-γ ELISPOT and intracellular cytokine staining. In conclusion, sustained functional neoantigen-specific T cell therapy combined with immune checkpoint targeting may be well suited to help control progressive metastatic pancreatic cancer.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Juan Du
- The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Baorui Liu
- The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China
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Wang X, Li L, Yang Y, Fan L, Ma Y, Mao F. Reveal the Heterogeneity in the Tumor Microenvironment of Pancreatic Cancer and Analyze the Differences in Prognosis and Immunotherapy Responses of Distinct Immune Subtypes. Front Oncol 2022; 12:832715. [PMID: 35252003 PMCID: PMC8891159 DOI: 10.3389/fonc.2022.832715] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 01/19/2022] [Indexed: 12/12/2022] Open
Abstract
Purpose The current clinical classification of pancreatic ductal adenocarcinoma (PDAC) cannot well predict the patient’s possible response to the treatment plan, nor can it predict the patient’s prognosis. We use the gene expression patterns of PDAC patients to reveal the heterogeneity of the tumor microenvironment of pancreatic cancer and analyze the differences in the prognosis and immunotherapy response of different immune subtypes. Methods Firstly, use ICGC’s PACA-AU PDAC expression profile data, combined with the ssGSEA algorithm, to analyze the immune enrichment of the patient’s tumor microenvironment. Subsequently, the spectral clustering algorithm was used to extract different classifications, the PDAC cohort was divided into four subtypes, and the correlation between immune subtypes and clinical characteristics and survival prognosis was established. The patient’s risk index is obtained through the prognostic prediction model, and the correlation between the risk index and immune cells is prompted. Results We can divide the PDAC cohort into four subtypes: immune cell and stromal cell enrichment (Immune-enrich-Stroma), non-immune enrichment but stromal cell enrichment (Non-immune-Stroma), immune-enriched Collective but non-matrix enrichment (Immune-enrich-non-Stroma) and non-immune enrichment and non-stromal cell enrichment (Non-immune-non-Stroma). The five-year survival rate of immune-enrich-Stroma and non-immune-Stroma of PACA-CA is quite different. TCGA-PAAD’s immune-enrich-Stroma and immune-enrich-non-Stroma groups have a large difference in productivity in one year. The results of the correlation analysis between the risk index and immune cells show that the patient’s disease risk is significantly related to epithelial cells, megakaryocyte-erythroid progenitor (MEP), and Th2 cells. Conclusion The tumor gene expression characteristics of pancreatic cancer patients are related to immune response, leading to morphologically recognizable PDAC subtypes with prognostic/predictive significance.
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Affiliation(s)
- Xiaoqin Wang
- Department of Clinical Laboratory, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- *Correspondence: Feifei Mao, ; Xiaoqin Wang,
| | - Lifang Li
- Emergency Department, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yang Yang
- Department of Hepatobiliary and Pancreatic Surgery, The First People’s Hospital of Changzhou, Changzhou, China
| | - Linlin Fan
- Department of Clinical Laboratory, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Ying Ma
- Department of Clinical Laboratory, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Feifei Mao
- Tongji University Cancer Center, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China
- *Correspondence: Feifei Mao, ; Xiaoqin Wang,
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Zheng T, Han W, Wang A, Wang Y. Functional mechanism of hsa-miR-128-3p in epithelial-mesenchymal transition of pancreatic cancer cells via ZEB1 regulation. PeerJ 2022; 10:e12802. [PMID: 35186455 PMCID: PMC8818272 DOI: 10.7717/peerj.12802] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 12/25/2021] [Indexed: 01/10/2023] Open
Abstract
Pancreatic cancer (PC) often correlates with high mortality due to late diagnosis, rapid metastasis, and resistance to chemotherapy. miR-128-3p has been validated as a tumor suppressor in PC. This study explored the functional mechanism of miR-128-3p in epithelial-mesenchymal transition (EMT) of PC cells. Four PC cancer cell lines with different degrees of malignancy and normal pancreatic cells were selected to detect expressions of hsa-miR-128-3p and ZEB1 by RT-qPCR and Western blot. miR-128-3p mimic or si-ZEB1 was delivered into PANC-1 cells and miR-128-3p inhibitor or oe-ZEB1 was delivered into AsPC-1 cells. Expressions of epithelial and mesenchymal markers were analyzed by Western blot and cell fluorescence staining. The binding relationship between miR-128-3p and ZEB1 was examined by bioinformatics analysis and dual-luciferase assay, and verified by RT-qPCR and Western blot. PC cell invasion and migration were assessed by Transwell assays. Generally, hsa-miR-128-3p was poorly-expressed in PC cells. However, it was relatively more expressed in AsPC-1 cells with epithelial phenotypes relative to PANC-1 cells with mesenchymal phenotype, whereas ZEB1 expression showed opposite tendencies. PANC-1 cells transfected with miR-128-3p mimic or si-ZEB1 showed upregulated E-cadherin and downregulated N-cadherin, and transformed from mesenchymal phenotypes to epithelial phenotypes, with decreased invasion and migration, while opposite results occurred in AsPC-1 cells transfected with miR-128-3p inhibitor or oe-ZEB1. miR-128-3p targeted ZEB1. oe-ZEB1 antagonized the inhibition of miR-128-3p mimic on PANC-1 cell EMT, invasion, and migration, while si-ZEB1 reversed the facilitation of miR-128-3p inhibitor in AsPC-1 cells. In conclusion, miR-128-3p inhibited PC cell EMT, invasion, and migration by targeting ZEB1.
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Affiliation(s)
- Tianying Zheng
- Medical Oncology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Wenfei Han
- Medical Oncology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Aijun Wang
- Medical Oncology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Yonggang Wang
- Medical Oncology, Qilu Hospital of Shandong University, Jinan, Shandong, China
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