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Xu N, Zhang T, Sun W, Ye C, Zhou H. Identification of an extracellular matrix signature for predicting prognosis and sensitivity to therapy of patients with gastric cancer. Sci Rep 2025; 15:7464. [PMID: 40032943 PMCID: PMC11876314 DOI: 10.1038/s41598-025-88376-8] [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] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Accepted: 01/28/2025] [Indexed: 03/05/2025] Open
Abstract
Extracellular matrix (ECM) is a vital component of the tumor microenvironment and plays a crucial role in the development and progression of gastric cancer (GC). Co-expression networks were established by means of the "WGCNA" package, the optimal model for extracellular matrix scores (ECMs) was developed and validated, with its accuracy in predicting the prognosis and treatment sensitivity of GC patients assessed. We performed univariate cox regression analysis [HR = 6.8 ( 3.3-14 ), p < 0.001] which demonstrated that ECMs was an independent risk character and perceptibly superior to other factors with further analysis of multivariate Cox regression [HR = 8.68 ( 4.16-18.08 ), p < 0.001]. The nomogram, presenting the clinical prognosis model for GC patients, demonstrated accuracy through KM analysis [HR = 3.97 (2.56-6.16), p < 0.001] and ROC curves with AUC values of 0.70, 0.72, and 0.72 at 1, 3, and 5 years, respectively. Using the ECMs model, we stratified GC patients into high- and low-risk groups, enabling precise predictions of prognosis and drug sensitivity. This stratification provides a new strategic direction for the personalized treatment of GC.
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Affiliation(s)
- Nan Xu
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Taojing Zhang
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Weiwei Sun
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Chenxiao Ye
- The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Huamiao Zhou
- Department of Medical Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China.
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Zhou J, Cai X, Lu Z, Xiong B, Peng C. Short-Term Safety Evaluation of Albumin-Bound Paclitaxel in Intraoperative and Postoperative Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer. J Gastrointest Cancer 2024; 55:877-887. [PMID: 38367177 DOI: 10.1007/s12029-024-01031-9] [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] [Accepted: 02/12/2024] [Indexed: 02/19/2024]
Abstract
PURPOSE To evaluate the short-term safety of albumin-bound paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) during and after gastric cancer (GC) surgery. METHODS A retrospective analysis of clinical data was conducted for GC surgery patients at Zhongnan Hospital of Wuhan University, from January 2020 to September 2022. The study group (n = 120) received HIPEC and the control group (n = 268) did not receive albumin-bound paclitaxel. Short-term safety indicators including intraoperative complications, hematological toxicity, liver and kidney function, and gastrointestinal function recovery were compared between the two groups. RESULTS There were no statistically significant differences between the two groups regarding intraoperative complications, hematological toxicity, liver and kidney function, and gastrointestinal function recovery time (P > 0.05 for all). In the study group, patients were further divided into subgroups based on dose and timing. Subgroup analysis revealed no significant differences among the different dose subgroups. However, when focusing on timing subgroups, the postoperative subgroup exhibited significantly higher white blood cell counts and bilirubin levels compared to the intraoperative subgroup, while the intraoperative subgroup had significantly higher bilirubin levels compared to both postoperative and intraoperative plus postoperative subgroups. CONCLUSION Albumin-bound paclitaxel demonstrates good safety and tolerability in HIPEC during and after GC surgery, without increasing the risk of intraoperative complications.
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Affiliation(s)
- Jingxiang Zhou
- Second Clinical College, Wuhan University, Wuhan , Hubei Province, 430070, China
- Department of Gastrointestinal Surgery, the Center for Minimally Invasive Surgery of Gastrointestinal Cancer, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan Peritoneal Cancer Clinical Medical Center, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Hubei Province, 430070, China
| | - Xiaopeng Cai
- Department of Gastrointestinal Surgery, the Center for Minimally Invasive Surgery of Gastrointestinal Cancer, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan Peritoneal Cancer Clinical Medical Center, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Hubei Province, 430070, China
| | - Zhao Lu
- Department of Gastrointestinal Surgery, the Center for Minimally Invasive Surgery of Gastrointestinal Cancer, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan Peritoneal Cancer Clinical Medical Center, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Hubei Province, 430070, China
| | - Bin Xiong
- Department of Gastrointestinal Surgery, the Center for Minimally Invasive Surgery of Gastrointestinal Cancer, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan Peritoneal Cancer Clinical Medical Center, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Hubei Province, 430070, China
| | - Chunwei Peng
- Department of Gastrointestinal Surgery, the Center for Minimally Invasive Surgery of Gastrointestinal Cancer, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan Peritoneal Cancer Clinical Medical Center, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Hubei Province, 430070, China.
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Chen W, Shi K, Liu J, Yang P, Han R, Pan M, Yuan L, Fang C, Yu Y, Qian Z. Sustained co-delivery of 5-fluorouracil and cis-platinum via biodegradable thermo-sensitive hydrogel for intraoperative synergistic combination chemotherapy of gastric cancer. Bioact Mater 2023; 23:1-15. [PMID: 36406247 PMCID: PMC9650011 DOI: 10.1016/j.bioactmat.2022.10.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 10/02/2022] [Accepted: 10/03/2022] [Indexed: 11/09/2022] Open
Abstract
Gastric cancer is the fifth most common cancer and the third leading cause of cancer death worldwide, posing a severe threat to human health. Surgical resection remains the most preferred option for gastric cancer treatment. However, for advanced gastric cancer, the curative effect of surgical resection is usually limited by the local recurrence, peritoneal carcinomatosis, or distal metastasis. Intraoperative chemotherapy is an attractive in situ adjuvant treatment strategy to reduce the recurrence and metastasis after surgical resection. Here, we designed a 5-fluorouracil (5-FU) and cis-platinum (DDP) co-delivery system based on a biodegradable temperature-sensitive hydrogel (PDLLA-PEG-PDLLA, PLEL) for intraoperative adjuvant combination chemotherapy of gastric cancer. This 5-FU + DDP/PLEL hydrogel system characterized by a special sol-gel phase transition in response to physiological temperature and presented sustained drug release in vitro and in vivo. A strong synergistic cell proliferation inhibition and apoptosis promotion of 5-FU + DDP/PLEL were observed against gastric cancer MKN45-luc cells. After intraperitoneal injection, the dual-drug loaded hydrogel formulation showed superior anti-tumor effects than the single-drug carrying hydrogels and combination of free 5-FU and DDP on the gastric cancer peritoneal carcinomatosis model. The use of hydrogel for dual-drug delivery had benefited to fewer side effects as well. What's more, we established a mouse model for postsurgical residual tumors and peritoneal carcinomatosis of gastric cancer, in which the intraoperative administration of 5-FU + DDP/PLEL also remarkably inhibited the local recurrence of the orthotopic tumors and the growth of the abdominal metastatic tumors, resulting in an extended lifetime. Hence, this developed dual-drug loaded hydrogel system has great potential in the intraoperative chemotherapy of gastric cancer, that suggests a clinically-relevant and valuable option for postsurgical management of gastric cancer.
Intraoperative chemotherapy could reduce the recurrence and metastasis after surgical resection of gastroenteric tumors. 5-FU and DDP co-delivery system based on PLEL was developed for intraoperative combination chemotherapy of gastric cancer. This dual-drug loaded hydrogel helped to improve synergistic anti-tumor effects and reduce adverse side effects in vivo. 5-FU+DDP/PLEL could inhibit recurrence of orthotopic tumors and growth of abdominal metastatic tumors in gastric cancer.
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Wu YZ, Wu M, Zheng XH, Wang BZ, Xue LY, Ding SK, Yang L, Ren JS, Tian YT, Xie YB. No long-term survival benefit with sustained-release 5-fluorouracil implants in patients with stages II and III gastric cancer. World J Gastroenterol 2022; 28:5589-5601. [PMID: 36304092 PMCID: PMC9594009 DOI: 10.3748/wjg.v28.i38.5589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 09/10/2022] [Accepted: 09/23/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The prognosis of gastric cancer in an advanced stage remains poor. The exact efficacy of the use of intraoperative sustained-release chemotherapy with 5-fluorouracil (5-FU) in advanced-stage gastric cancer is still unelucidated. AIM To explore the long-term survival benefit of using sustained-release 5-FU implants in stage II and stage III gastric cancer patients. METHODS Patients with gastric cancer in a locally advanced stage and who underwent an R0 radical resection between Jan 2014, to Dec 2016, in this single institution were included. Patients with pathological diagnoses other than adenocarcinoma were excluded. All included patients were grouped according to whether intraoperative sustained-release (SR) chemotherapy with 5-FU was used or not (NSR). The primary end-point was 5-year overall survival. Kaplan-Meier method with log-rank test was used to analyze the overall survival of patients and Cox analysis was used to analyze prognosis factors of these patients. RESULTS In total, there were 563 patients with gastric cancer with locally advanced stage, who underwent an R0 radical resection. 309 patients were included in the final analysis. 219 (70.9%) were men, with an average age of 58.25 years. Furthermore, 56 (18.1%) received neoadjuvant chemotherapy, and 191 (61.8%) were in TNM stage III. In addition, 158 patients received intraoperative sustained-release chemotherapy with 5-FU and were included in the SR group, while the other 161 patients were included in the NSR group. The overall complication rate was 12.94% in the whole group and 10.81%, 16.46% in SR and NSR groups, respectively. There were no significant differences between the two groups in overall survival and complication rate (P > 0.05). The multivariate cox analysis indicated that only N Stage and neoadjuvant therapy were independent influencing factors of survival. CONCLUSION Intraoperative sustained-release chemotherapy usage with 5-FU, did not improve the survival of patients who underwent an R0 radical resection in locally advanced stage of gastric cancer.
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Affiliation(s)
- Yun-Zi Wu
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ming Wu
- Department of Gastrointestinal Surgery, Yun Cheng Center Hospital, Yuncheng 044000, Shanxi Province, China
| | - Xiao-Hao Zheng
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Bing-Zhi Wang
- Department of Pathology, National Cancer Center/National Clinical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Li-Yan Xue
- Department of Pathology, National Cancer Center/National Clinical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Shi-Kang Ding
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Lin Yang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jian-Song Ren
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yan-Tao Tian
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yi-Bin Xie
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Hebei Cancer Hospital, Chinese Academy of Medical Sciences, Langfang 065001, Hebei Province, China
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Implants as Targeted Drug Delivery Systems (Review). Pharm Chem J 2022. [DOI: 10.1007/s11094-022-02649-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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