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Du XY, Xia RJ, Shen LW, Ma JG, Yao WQ, Xu W, Lin ZP, Ma LB, Niu GQ, Fan RF, Xu SM, Yan L. Quadruple therapy with immunotherapy and chemotherapy as first-line conversion treatment for unresectable advanced gastric adenocarcinoma: A case report. World J Gastrointest Oncol 2025; 17:102258. [DOI: 10.4251/wjgo.v17.i4.102258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 01/20/2025] [Accepted: 02/24/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND The treatment of gastric cancer remains highly challenging, particularly in cases of unresectable locally advanced or metastatic disease. Although chemotherapy and immunotherapy have shown some efficacy in such patients, significant limitations persist in extending survival and enhancing safety. To address these challenges, we designed an innovative first-line quadruple conversion therapy regimen that integrates a programmed cell death protein 1 (PD-1) inhibitor with chemotherapy, and we successfully implemented this therapy regimen in the treatment of a patient with unresectable locally advanced gastric adenocarcinoma.
CASE SUMMARY We report the case of a 55-year-old male who was diagnosed with unresectable locally advanced gastric adenocarcinoma and presented with intermittent epigastric pain and multiple lymph node metastases in the abdominal cavity, with the metastasis being notably large in size. The tumor tissue was negative for human epidermal growth factor receptor 2 by immunohistochemistry. Considering the patient's status, the multidisciplinary team decided to administer sintilimab in combination with albumin-bound paclitaxel (nab-paclitaxel), S-1, and oxaliplatin as a quadruple drug conversion therapy. After 4 cycles of conversion therapy, the patient's epigastric pain was significantly alleviated, his stool color normalized, the volume of the primary tumor and lymph node metastases was markedly reduced, and the tumor marker levels decreased to within the normal range. The patient subsequently underwent laparoscopic total gastrectomy with abdominal lymph node dissection, and postoperative pathological biopsy revealed a pathological complete response and R0 resection, after which the patient recovered to an excellent physical status.
CONCLUSION To the best of our knowledge, this is the first reported case of unresectable locally advanced gastric adenocarcinoma successfully treated with quadruple therapy with a PD-1 inhibitor and chemotherapy as a first-line conversion regimen. This first-line conversion therapy with the quadruple regimen may be effective and safe for unresectable locally advanced gastric adenocarcinoma.
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Affiliation(s)
- Xiao-Yu Du
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Medicine, Northwest Minzu University, Lanzhou 730050, Gansu Province, China
| | - Ren-Jie Xia
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Medicine, Northwest Minzu University, Lanzhou 730050, Gansu Province, China
| | - Li-Wen Shen
- Department of Medical Support Center, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Jian-Guo Ma
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
- First School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou 730030, Gansu Province, China
| | - Wei-Qing Yao
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Medicine, Northwest Minzu University, Lanzhou 730050, Gansu Province, China
| | - Wei Xu
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Zhi-Peng Lin
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Liang-Bin Ma
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Guo-Qiang Niu
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Rui-Fang Fan
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Shu-Mei Xu
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Long Yan
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
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Wei J, Ji K, Zhang Y, Zhang J, Wu X, Ji X, Zhou K, Yang X, Lu H, Wang A, Bu Z. Exploration of molecular markers related to chemotherapy efficacy of hepatoid adenocarcinoma of the stomach. Cell Oncol (Dordr) 2024; 47:677-693. [PMID: 37943484 DOI: 10.1007/s13402-023-00892-9] [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] [Accepted: 10/08/2023] [Indexed: 11/10/2023] Open
Abstract
PURPOSE Preoperative neoadjuvant chemotherapy may not improve the prognosis of patients with hepatoid adenocarcinoma of the stomach (HAS), a rare pathological type of gastric cancer. Thus, the study aimed at the genomic and transcriptomic impacts of preoperative chemotherapy on HAS. METHODS Patients with HAS who underwent surgical resection at Peking University Cancer Hospital were retrospectively included in this study. Whole exome sequencing and transcriptome sequencing were performed on pre-chemotherapy, non-chemotherapy and post-chemotherapy samples. We then compared the alterations in molecular markers between the post-chemotherapy and non-chemotherapy groups, and between the chemotherapy-effective and chemotherapy-ineffective groups, respectively. RESULTS A total of 79 tumor samples from 72 patients were collected. Compared to the non-chemotherapy group, the mutation frequencies of several genes were changed after chemotherapy, including TP53. In addition, there was a significant increase in the frequency of frameshift mutations and cytosine transversion to adenine (C > A), appearance of COSMIC signature 6 and 14, and a reduced gene copy number amplification. Interestingly, the same phenomenon was observed in chemotherapy-ineffective patients. In addition, many HAS patients had ERBB2, FGFR2, MET and HGF gene amplification. Moreover, the expression of immune-related genes, especially those related to lymphocyte activation, was down-regulated after chemotherapy. CONCLUSION Chemotherapy is closely associated with changes in the molecular characteristics of HAS. After chemotherapy, at genomic and transcriptome level, many features were altered. These changes may be molecular markers of poor chemotherapeutic efficacy and play an important role in chemoresistance in HAS. In addition, ERBB2, FGFR2, MET and HGF gene amplification may be potential therapeutic targets for HAS.
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Affiliation(s)
- Jingtao Wei
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Ke Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Yue Zhang
- Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Animal Experimental Centre, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
- The Cardiomyopathy Research Group at Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Beijing, 100037, China
| | - Ji Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Xiaojiang Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Xin Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Kai Zhou
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Xuesong Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Hongfeng Lu
- Berry Genomics Corporation, Beijing, 102206, China
| | - Anqiang Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China.
| | - Zhaode Bu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China.
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Feng D, Wang J, Xiao Y, Wu R, Li D, Tuo Z, Yu Q, Ye L, MIYAMOTO A, Yoo KH, Wei W, Ye X, Zhang C, Han P. SKA3 targeted therapies in cancer precision surgery: bridging bench discoveries to clinical applications - review article. Int J Surg 2024; 110:2323-2337. [PMID: 38241327 PMCID: PMC11020031 DOI: 10.1097/js9.0000000000001123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 01/09/2024] [Indexed: 01/21/2024]
Abstract
Spindle and kinetochore-associated complex subunit 3 (SKA3) is a microtubule-binding subcomplex of the outer kinetochore, which plays a vital role in proper chromosomal segregation and cell division. Recently, SKA3 have been demonstrated its oncogenic role of tumorigenesis and development in cancers. In this review, the authors comprehensively deciphered SKA3 in human cancer from various aspects, including bibliometrics, pan-cancer analysis, and narrative summary. The authors also provided the top 10 predicted drugs targeting SKA3. The authors proposed that SKA3 was a potential target and brought new therapeutic opportunities for cancer patients.
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Affiliation(s)
- Dechao Feng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu
- Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou
| | - Jie Wang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu
| | - Yuhan Xiao
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu
| | - Ruicheng Wu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu
| | - Dengxiong Li
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu
| | - Zhouting Tuo
- Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei
| | - Qingxin Yu
- Department of Pathology, Ningbo Clinical Pathology Diagnosis Center, Ningbo City, Zhejiang Province
| | - Luxia Ye
- Department of Public Research Platform, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, People’s Republic of China
| | - Akira MIYAMOTO
- Department of Rehabilitation, West Kyushu University, Japan
| | - Koo Han Yoo
- Department of Urology, Kyung Hee University, South Korea
| | - Wuran Wei
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu
| | - Xing Ye
- Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Chi Zhang
- Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou
| | - Ping Han
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu
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Lin T, Chen X, Xu Z, Hu Y, Liu H, Yu J, Li G. Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for gastric cancer with intraoperative detection of limited peritoneal metastasis: a Phase II study of CLASS-05 trial. Gastroenterol Rep (Oxf) 2024; 12:goae001. [PMID: 38390578 PMCID: PMC10882263 DOI: 10.1093/gastro/goae001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 10/05/2023] [Accepted: 12/31/2023] [Indexed: 02/24/2024] Open
Abstract
Background Systemic chemotherapy for gastric cancer with peritoneal metastasis has limited clinical benefit; for those with intraoperative detection of occult peritoneal metastasis, cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is an alternative treatment. However, the feasibility and effects of this modality and criteria for selecting suitable groups remain unclear. This study aimed to explore the safety and efficacy of laparoscopic cytoreductive surgery (L-CRS) followed by HIPEC in gastric cancer with limited peritoneal metastasis, and this study also aimed to determine the optimized cut-off of the peritoneal cancer index. Methods Between March 2017 and November 2019, patients diagnosed with gastric cancer peritoneal metastases by using laparoscopy and the Sugarbaker peritoneal cancer index of ≤12 were eligible for inclusion. All patients received L-CRS (including gastrectomy with D2 lymph node dissection) and resection of visible peritoneal metastasis, followed by post-operative HIPEC, and systemic chemotherapy. The primary end points were median progression-free survival and median survival time, and the secondary outcomes were morbidity and mortality within 30 days after surgery. Results Thirty patients were eligible for analysis, of whom 19 (63.3%) were female, and the overall mean age was 53.0 years. The post-operative morbidity was 20% and the severe complication rate was 10%. The median survival time was 27.0 months with a 2-year overall survival rate of 52.3% and median progression-free survival was 14.0 months with a 2-year progression-free survival of 30.4%. Conclusions L-CRS followed by HIPEC can be safely performed for gastric cancer with limited peritoneal metastasis and potential survival benefits.
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Affiliation(s)
- Tian Lin
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, P. R. China
| | - Xinhua Chen
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, P. R. China
| | - Zhijun Xu
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, P. R. China
| | - Yanfeng Hu
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, P. R. China
| | - Hao Liu
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, P. R. China
| | - Jiang Yu
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, P. R. China
| | - Guoxin Li
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, P. R. China
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Huan X, Zou K, Zhang P, Ding H, Luo C, Xiang C, Xu S, Zhuang Y, Wu C, Wang Y, Wu X, Chen C, Zhang J, Yao X, Liu F, Liu S, Wu Z. Neoadjuvant chemotherapy is linked to an amended anti-tumorigenic microenvironment in gastric cancer. Int Immunopharmacol 2024; 127:111352. [PMID: 38091833 DOI: 10.1016/j.intimp.2023.111352] [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: 10/07/2023] [Revised: 12/05/2023] [Accepted: 12/05/2023] [Indexed: 01/18/2024]
Abstract
BACKGROUND Neoadjuvant chemotherapy (NAC) is a frequently intervention for patients with locally advanced gastric cancer (GC). Nevertheless, its impact on the tumor immune microenvironment remains unclear. METHODS We used immunohistochemistry to identify T-cell subpopulations, tumor-associated neutrophils (TANs), and tumor-associated macrophages (TAMs) in the GC microenvironment (GCME) among paired samples (pre-chemotherapy and post-chemotherapy) from 48 NAC-treated patients. Multiplex immunofluorescence (mIF) was performed to assess immune biomarkers, including CK, CD4, CD8, FOXP3, PD1, PD-L1, CD163, CD86, myeloperoxidase and Arginase-1 in paired samples from 6 GC patients whose response to NAC were rigorously defined. RESULTS NAC was intricately linked to enhanced CD8+:CD4+ ratio, reduced CD163+ M2-like macrophages, augmented CD86+ M1: CD163+ M2-like macrophage ratio, and diminished FOXP3+ regulatory T cells (T-regs) and TANs density. Based on mIF, PD1+CD8+T-cells, FOXP3+T-regs, PD-L1+ TANs, and CD163+ M2-like macrophages exhibited marked reduction and greater co-localization with tumor cells following NAC. The pre-NAC FOXP3+ T-regs and CD163+ M2-like macrophages content was substantially elevated in the response cohort, whereas, the post-NAC CD8+:CD4+ and CD86+ M1: CD163+ M2-like macrophage ratios were intricately linked to the tumor pathologic response. We observed greater CD163+ M2-like macrophages and tumor cells co-localization following NAC, which was correlated with tumor pathologic response. Lastly, multivariate analysis revealed that post-NAC CD8+:CD4+ and CD86+ M1: CD163+ M2-like macrophage ratios were stand-alone indicators of positive patient prognosis. CONCLUSIONS NAC converts the GCME to an anti-tumorigenic state that is conducive to enhanced patient outcome. These finding can significantly benefit the future planning of highly efficacious and personalized GC immunotherapy.
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Affiliation(s)
- Xiangkun Huan
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
| | - Kun Zou
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
| | - Peichan Zhang
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China; No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Haihua Ding
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China; No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Chunyang Luo
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China; No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Chunjie Xiang
- School of Medicine, Southeast University, Nanjing 210023, China
| | - Shuo Xu
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Yuwen Zhuang
- Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
| | - Cunen Wu
- Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
| | - Yaohui Wang
- Department of Pathology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
| | - Xiaoyu Wu
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
| | - Che Chen
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
| | - Junfeng Zhang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Xuequan Yao
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
| | - Fukun Liu
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
| | - Shenlin Liu
- Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
| | - Zhenfeng Wu
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.
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Deng Z, Guo T, Bi J, Wang G, Hu Y, Du H, Zhou Y, Jia S, Xing X, Ji J. Transcriptome profiling of patient-derived tumor xenografts suggests novel extracellular matrix-related signatures for gastric cancer prognosis prediction. J Transl Med 2023; 21:638. [PMID: 37726803 PMCID: PMC10510236 DOI: 10.1186/s12967-023-04473-0] [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: 05/16/2023] [Accepted: 08/27/2023] [Indexed: 09/21/2023] Open
Abstract
BACKGROUND A major obstacle to the development of personalized therapies for gastric cancer (GC) is the prevalent heterogeneity at the intra-tumor, intra-patient, and inter-patient levels. Although the pathological stage and histological subtype diagnosis can approximately predict prognosis, GC heterogeneity is rarely considered. The extracellular matrix (ECM), a major component of the tumor microenvironment (TME), extensively interacts with tumor and immune cells, providing a possible proxy to investigate GC heterogeneity. However, ECM consists of numerous protein components, and there are no suitable models to screen ECM-related genes contributing to tumor growth and prognosis. We constructed patient-derived tumor xenograft (PDTX) models to obtain robust ECM-related transcriptomic signatures to improve GC prognosis prediction and therapy design. METHODS One hundred twenty two primary GC tumor tissues were collected to construct PDTX models. The tumorigenesis rate and its relationship with GC prognosis were investigated. Transcriptome profiling was performed for PDTX-originating tumors, and least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to extract prognostic ECM signatures and establish PDTX tumorigenicity-related gene (PTG) scores. The predictive ability of the PTG score was validated using two independent cohorts. Finally, we combined PTG score, age, and pathological stage information to establish a robust nomogram for GC prognosis prediction. RESULTS We found that PDTX tumorigenicity indicated a poor prognosis in patients with GC, even at the same pathological stage. Transcriptome profiling of PDTX-originating GC tissues and corresponding normal controls identified 383 differentially expressed genes, with enrichment of ECM-related genes. A robust prognosis prediction model using the PTG score showed robust performance in two validation cohorts. A high PTG score was associated with elevated M2 polarized macrophage and cancer-associated fibroblast infiltration. Finally, combining the PTG score with age and TNM stage resulted in a more effective prognostic model than age or TNM stage alone. CONCLUSIONS We found that ECM-related signatures may contribute to PDTX tumorigenesis and indicate a poor prognosis in GC. A feasible survival prediction model was built based on the PTG score, which was associated with immune cell infiltration. Together with patient ages and pathological TNM stages, PTG score could be a new approach for GC prognosis prediction.
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Affiliation(s)
- Ziqian Deng
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Ting Guo
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Jiwang Bi
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Gangjian Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Ying Hu
- Biological Sample Bank, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Hong Du
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Yuan Zhou
- Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University, Beijing, 100191, People's Republic of China.
| | - Shuqin Jia
- Department of Molecular Diagnosis, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China.
| | - Xiaofang Xing
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China.
| | - Jiafu Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China.
- Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China.
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Chen Y, Yang Z, Zhao M, Xu C, Zhu Y, Zhang H, Huang H, Peng Y, Hu Y, Lin T, Chen T, Chen H, Zhao L, Liu H, Li G, Yu J, Chen X. Impact of preoperative therapy on surgical outcomes of laparoscopic total gastrectomy for gastric/gastroesophageal junction cancer. Chin J Cancer Res 2023; 35:354-364. [PMID: 37691897 PMCID: PMC10485917 DOI: 10.21147/j.issn.1000-9604.2023.04.03] [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: 05/28/2023] [Accepted: 08/08/2023] [Indexed: 09/12/2023] Open
Abstract
Objective As laparoscopic surgery is widely applied for primarily treated gastric cancer (GC)/gastroesophageal junction cancer (GEJC) and gains many advantages, the feasibility of laparoscopic total gastrectomy (LTG) for GC/GEJC patients who have received preoperative therapy (PT) has come to the fore. This study aims to analyze the safety and feasibility of LTG after PT for GC/GEJC patients. Methods We retrospectively analyzed the data of 511 patients with GC/GEJC undergoing LTG, of which 405 received LTG (LTG group) and 106 received PT+LTG (PT-LTG group) at Nanfang Hospital between June 2018 and September 2022. The surgical outcomes were compared between the two groups. Results The surgical duration was significantly longer in the PT-LTG group (P<0.001), while the incidence of intraoperative complications (P=1.000), postoperative complications (LTG group vs. PT-LTG group: 26.2% vs. 23.6%, P=0.587), the classification of complication severity (P=0.271), and postoperative recovery was similar between two groups. Notably, the incidence of anastomotic complications of esophagojejunostomy was also comparable between the two groups (LTG group vs. PT-LTG group: 5.9% vs. 5.7%, P=0.918). The univariate and multivariate analysis confirmed that positive proximal margin [positive vs. negative: odds ratio (OR)=14.094, 95% confidence interval (95% CI): 2.639-75.260, P=0.002], rather than PT, has an impact on anastomotic complications after LTG (OR=0.945, 95% CI: 0.371-2.408, P=0.905). Conclusions PT did not increase the surgical risk of LTG for GC/GEJC. Therefore, considering the positive effect of PT on long-term survival, the broader application of PT and LTG for GC/GEJC is supported by our findings.
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Affiliation(s)
- Yuehong Chen
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, the First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
| | - Zhijing Yang
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, the First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
| | - Mingli Zhao
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, the First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
| | - Chuanjin Xu
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, the First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
| | - Yuxuan Zhu
- The First Clinical Medical School, Southern Medical University, Guangzhou 510515, China
| | - Huimin Zhang
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, the First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
| | - Huilin Huang
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, the First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
| | - Yanmei Peng
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, the First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
| | - Yanfeng Hu
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, the First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
| | - Tian Lin
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, the First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
| | - Tao Chen
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, the First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
| | - Hao Chen
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, the First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
| | - Liying Zhao
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, the First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
| | - Hao Liu
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, the First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
| | - Guoxin Li
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, the First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
| | - Jiang Yu
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, the First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
| | - Xinhua Chen
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, the First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
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He Q, Huangfu L, Fan B, Zhuang Q, He L, Li L, You W, Xing X. T-cells infiltration mediates the association between neutrophil/lymphocyte ratio and survival in gastric cancer. Cancer Med 2023; 12:15893-15902. [PMID: 37306187 PMCID: PMC10469634 DOI: 10.1002/cam4.6228] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 05/15/2023] [Accepted: 06/01/2023] [Indexed: 06/13/2023] Open
Abstract
BACKGROUND Neutrophil/lymphocyte ratio (NLR) is a vital index for systemic inflammation and a prognostic indicator for gastric cancer (GC). Despite the abundant literature on NLR's prognostic value for GC, the underlying factors mediating its impact on survival remain unclear. The objective of this study was to analyze the role of NLR in different prognostic models and subgroups, and investigate the mediating effects of immune infiltrates between NLR and survival. METHODS A total of 924 patients who underwent D2 lymph node resection were enrolled in this study. According to the level of NLR, patients were divided into two groups, the high and low NLR groups. Clinical parameters, indexes related to immune infiltrates, and survival were compared between the two groups. Prognostic models, interaction analysis, and mediating effects analysis were performed to investigate the clinical association of NLR, immune infiltrates, and survival. RESULTS The infiltration of CD3+ and CD8+ T cells was significantly different in the two NLR groups. The level of NLR was an independent prognostic predictor of GC. In addition, an interaction effect exists between NLR and MMR status on the prognosis of GC (p-interaction <0.01). Lastly, the mediating effect analysis revealed that the infiltration level of CD3+ T cells was the mediating factor between NLR and survival (p < 0.001). CONCLUSIONS The level of NLR is an independent prognostic predictor of GC. The effect of NLR on prognosis is partly mediated by CD3+ T-cell infiltration.
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Affiliation(s)
- Qifei He
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer CenterPeking University Cancer Hospital and InstituteBeijingChina
- Department of Bone Joint and Musculoskeletal TumorThe First Affiliated Hospital of Shenzhen University, Shenzhen Second People's HospitalShenzhenChina
| | - Longtao Huangfu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer CenterPeking University Cancer Hospital and InstituteBeijingChina
| | - Biao Fan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer CenterPeking University Cancer Hospital and InstituteBeijingChina
| | - Qianzheng Zhuang
- Department of Bone Joint and Musculoskeletal TumorThe First Affiliated Hospital of Shenzhen University, Shenzhen Second People's HospitalShenzhenChina
| | - Liu He
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer CenterPeking University Cancer Hospital and InstituteBeijingChina
| | - Lin Li
- Department of Gastroenterology, Aerospace Center HospitalPeking University Aerospace School of Clinical MedicineBeijingChina
| | - Wei You
- Department of Bone Joint and Musculoskeletal TumorThe First Affiliated Hospital of Shenzhen University, Shenzhen Second People's HospitalShenzhenChina
| | - Xiaofang Xing
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer CenterPeking University Cancer Hospital and InstituteBeijingChina
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Pang HY, Yan MH, Chen LH, Chen XF, Chen ZX, Zhang SR, Sun H. Detection of asymptomatic recurrence following curative surgery improves survival in patients with gastric cancer: A systematic review and meta-analysis. Front Oncol 2022; 12:1011683. [PMID: 36387075 PMCID: PMC9643694 DOI: 10.3389/fonc.2022.1011683] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 10/10/2022] [Indexed: 12/02/2022] Open
Abstract
Background To date, there is no evidence that intensive follow-up provides survival benefit in gastric cancer patients undergoing curative gastrectomy. The aim of this study is to investigate the efficacy of detection of asymptomatic recurrence using intensive surveillance strategy in long-term survival after curative gastric cancer surgery. Methods A systematic review of electronic databases including PubMed, Embase, Web of Science, the Cochrane Library and China National Knowledge Infrastructure, Clinical Trials Registry and Google Scholar was performed up to April 2022. The primary outcomes were survival outcomes: overall survival, recurrence-free survival and post-recurrence survival. The secondary endpoints were clinicopathological features, recurrence patterns and treatment after recurrence. The registration number of this protocol is PROSPERO CRD42022327370. Results A total of 11 studies including 1898 participants were included. In the pooled analysis, the detection of asymptomatic recurrence was significantly associated with an improved overall survival compared to patients showing symptoms of recurrence (HR=0.67; 95%CI: 0.57-0.79; P<0.001), which was primarily driven by the prolongation of post-recurrence survival (HR=0.51; 95%CI: 0.42-0.61; P<0.001), since there was no significant difference observed in recurrence-free survival (HR=1.12; 95%CI: 0.81-1.55; P=0.48) between the two groups. Meanwhile, male sex and advanced T stage were more frequently observed in the symptomatic recurrence group. Furthermore, patients in the symptomatic recurrence group had a higher proportion of peritoneal relapse but lower proportion of distant lymph node metastasis. Additionally, patients in the symptomatic recurrence group were less likely to receive surgery treatment and post-recurrence chemotherapy. Conclusion The detection of asymptomatic recurrence using intensive follow-up was associated with an appreciable improvement in overall survival. However, more robust data from high-quality studies are still required to verify this issue. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=327370, identifier CRD42022327370.
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