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Ren S, Wei Y, Liu W, Zhang Y, Wang Y, Yang J, Liu B, Shi T, Wei J. Clinical Characteristics, Prognostic Factors and Therapeutic Strategies in Gastric Cancer Patients With Bone Metastasis: A Retrospective Analysis. Cancer Med 2025; 14:e70781. [PMID: 40105370 PMCID: PMC11921140 DOI: 10.1002/cam4.70781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 02/09/2025] [Accepted: 03/07/2025] [Indexed: 03/20/2025] Open
Abstract
BACKGROUND Bone metastases are highly refractory and are associated with extremely poor survival. Despite the increasing incidence of bone metastasis in gastric cancer (GC), comprehensive analyses regarding the clinicopathological features, prognosis, and treatment of bone-metastatic GC remain limited. METHODS We obtained data from 120 bone-metastatic GC patients from Nanjing Drum Tower Hospital and 36,139 GC patients from the SEER database. Chi-square and Mann-Whitney U-tests evaluated clinicopathological features, while Cox models identified prognostic factors. Kaplan-Meier curves and forest plots assessed the effects of different treatment strategies on overall survival after bone metastasis (OS-BM). RESULTS Among 120 bone-metastatic GC patients, 55 (45.83%) were diagnosed with poorly cohesive gastric carcinoma (PCC). The higher incidence of bone metastasis was also observed in SRCC patients from the SEER database (p < 0.0001). PCC patients exhibited distinct pathological features compared to non-PCC patients, including lower PD-L1 (p = 0.042) and E-cadherin expression (p = 0.049). Multivariate analysis identified various negative prognostic factors such as metachronous bone metastasis (p < 0.001, HR = 2.35, 95% CI:1.47-3.74) and CA125 expression (p = 0.036, HR = 1.60, 95% CI:1.03-2.48), whereas immunotherapy was a positive prognostic factor (p < 0.001, HR = 0.44, 95% CI:0.29-0.66). Subgroup analysis also showed improved survival among different populations of bone-metastatic GC patients receiving immunotherapy. Moreover, combinational therapies including immunotherapy and other treatments (anti-angiogenic therapy and/or local radiotherapy) further improved patient OS-BM. CONCLUSION Our results suggest bone-metastatic GC patients exhibit distinct clinicopathological features, with a high incidence of bone metastasis in PCC. Immunotherapy-based combination therapies offer improved survival benefits, thus supporting the application of immunotherapy in GC patients at high risk of bone metastasis.
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Affiliation(s)
- Shiji Ren
- Department of OncologyNanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityNanjingChina
| | - Yutao Wei
- Department of OncologyNanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese MedicineNanjingChina
| | - Wenqi Liu
- Department of OncologyNanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjingChina
| | - Yipeng Zhang
- Department of OncologyNanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityNanjingChina
| | - Yue Wang
- Department of OncologyNanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityNanjingChina
| | - Ju Yang
- Department of OncologyNanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityNanjingChina
| | - Baorui Liu
- Department of OncologyNanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityNanjingChina
| | - Tao Shi
- Department of OncologyNanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityNanjingChina
| | - Jia Wei
- Department of OncologyNanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityNanjingChina
- Department of OncologyNanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese MedicineNanjingChina
- Nanjing Medical Key Laboratory of OncologyNanjingChina
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Wang SY, Wang JH, Chen RK, Yuan Z, Cui H, Wei B, Cui JX. Mapping the landscape of gastric signet ring cell carcinoma: Overcoming hurdles and charting new paths for advancement. World J Clin Oncol 2025; 16:98983. [PMID: 39995554 PMCID: PMC11686557 DOI: 10.5306/wjco.v16.i2.98983] [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: 07/10/2024] [Revised: 09/26/2024] [Accepted: 11/13/2024] [Indexed: 12/11/2024] Open
Abstract
BACKGROUND In recent years, the global prevalence of gastric cancer (GC) has witnessed a progressive decrease, accompanied by a step-growth in the incidence of gastric signet ring cell carcinoma (GSRCC). As precision medicine concepts progress, GSRCC, a distinct sub-type of GC, has drawn considerable attention from researchers. However, there still persist some controversies regarding the associated research findings. AIM To summarize the current obstacles and potential future directions for research on GSRCC. METHODS To begin with, all literature related to GSRCC published from January 1, 2004 to December 31, 2023 was subjected to bibliometric analysis in this article. Additionally, this paper analyzed the research data using CiteSpace, GraphPad Prism v8.0.2, and VOSviewer, which was obtained from the Web of Science Core Collection database. The analysis results were visually represented. RESULTS This study provided a comprehensive overview of the statistical characteristics of the 995 English articles related to GSRCC, including cited references, authors, journals, countries, institutions, and keywords. The popular keywords and clusters contain "prognosis", "survival", "expression", "histology", and "chemotherapy". CONCLUSION The prognosis, precise definition and classification, as well as chemoresistance of GSRCC, continue to be crucial areas of ongoing research, whose directions are closely tied to advancements in molecular biology research on GSRCC.
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Affiliation(s)
- Shu-Yuan Wang
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Jing-Hang Wang
- School of Medicine, Nankai University, Tianjin 300071, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Run-Kai Chen
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Zhen Yuan
- School of Medicine, Nankai University, Tianjin 300071, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Hao Cui
- School of Medicine, Nankai University, Tianjin 300071, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Bo Wei
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Jian-Xin Cui
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
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Yu C, Yang J, Li H, Wang J, Jin K, Li Y, Zhang Z, Zhou J, Tang Y. Prognostic prediction and treatment options for gastric signet ring cell carcinoma: a SEER database analysis. Front Oncol 2024; 14:1473798. [PMID: 39497709 PMCID: PMC11532132 DOI: 10.3389/fonc.2024.1473798] [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: 07/31/2024] [Accepted: 10/02/2024] [Indexed: 11/07/2024] Open
Abstract
Background In recent years, the overall incidence of gastric cancer has decreased. However, the incidence of gastric signet ring cell carcinoma (SRCC) is still increasing year by year. Compared with other subtypes (non-SRCC) such as adenocarcinoma, SRCC usually exhibits a more aggressive biological behavior. Therefore, studying the prognostic differences and factors associated with SRCC is essential to improve the accuracy of diagnosis and prognosis. The purpose of this study was to investigate the prognostic factors influencing the prognosis of patients with SRCC and to develop personalized treatments for different subgroups of patients. Methods The data on gastric SRCC patients and gastric adenocarcinoma (AC) patients from 1992 to 2020 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The data of gastric SRCC as the external validation group was reviewed from the First Affiliated Hospital of Soochow University. The overall survival (OS) and cancer specific survival (CSS) at 1 and 2 years were predicted for SRCC patients by constructing prognostic nomograms. A series of validation methods, including Akaike information criterion (AIC), decision curve analysis (DCA), calibration curve analysis, the concordance index (C-index) and the area under the receiver operating characteristic (AUC) curve, were used to verify the accuracy and reliability of the models. Results In all, 549 patients with SRCC were included after propensity score matching (PSM). Multivariate Cox regression analysis showed that T stage, N stage, M stage and surgical approach were independent risk factors affecting the prognosis of SRCC patients. A prognostic nomogram was constructed and validated as an accurate model for SRCC patients after scoring by receiver operating characteristic curve (ROC) curves and calibration plots. The patients were further divided into high-risk and low-risk groups, and the Kaplan-Meier curves showed that SRCC patients in the low-risk group could receive only surgery without chemotherapy, while chemotherapy plus surgery was a better option for SRCC patients in the high-risk group. Conclusion The prognosis for SRCC was less favorable than that of AC in terms of CSS. The nomograms were developed and validated to predict OS and CSS in patients with SRCC, helping in developing appropriate individualized treatment schedules.
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Affiliation(s)
- Chengqing Yu
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jian Yang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
- State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China
| | - Haoran Li
- Department of Gastrointestinal Surgery, Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou Medical Center, Changzhou, China
| | - Jie Wang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Kanghui Jin
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yifan Li
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Zixiang Zhang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jian Zhou
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
- State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China
| | - Yuchen Tang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
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Xie YQ, Li CC, Yu MR, Cao J. Immunosuppressive tumor microenvironment in gastric signet-ring cell carcinoma. World J Clin Oncol 2024; 15:1126-1131. [PMID: 39351457 PMCID: PMC11438843 DOI: 10.5306/wjco.v15.i9.1126] [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: 05/27/2024] [Revised: 07/29/2024] [Accepted: 08/12/2024] [Indexed: 08/29/2024] Open
Abstract
Gastric signet-ring cell carcinoma (GSRCC) is a subtype of gastric cancer with distinct phenotype and high risk of peritoneal metastasis. Studies have shown that early GSRCC has a good prognosis, while advanced GSRCC is insensitive to radiotherapy, chemotherapy or immune checkpoint blockade therapy. With technological advancement of single-cell RNA sequencing analysis and cytometry by time of flight mass cytometry, more detailed atlas of tumor microenvironment (TME) in GSRCC and its association with prognosis could be investigated extensively. Recently, two single-cell RNA sequencing studies revealed that GSRCC harbored a unique TME, manifested as highly immunosuppressive, leading to high immune escape. The TME of advanced GSRCC was enriched for immunosuppressive factors, including the loss of CXCL13 +-cluster of differentiation 8+-Tex cells and declined clonal crosstalk among populations of T and B cells. In addition, GSRCC was mainly infiltrated by follicular B cells. The increased proportion of SRCC was accompanied by a decrease in mucosa-associated lymphoid tissue-derived B cells and a significant increase in follicular B cells, which may be one of the reasons for the poor prognosis of GSRCC. By understanding the relationship between immunosuppressive TME and poor prognosis in GSRCC and the underlying mechanism, more effective immunotherapy strategies and improved treatment outcomes of GSRCC can be anticipated.
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Affiliation(s)
- Yu-Qiong Xie
- Center for Basic and Translational Research, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China
| | - Chun-Chun Li
- Center for Basic and Translational Research, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China
| | - Mei-Rong Yu
- Center for Basic and Translational Research, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China
| | - Jiang Cao
- Center for Basic and Translational Research, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China
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Xu J, Yu B, Wang F, Yang J. Single-cell RNA sequencing to map tumor heterogeneity in gastric carcinogenesis paving roads to individualized therapy. Cancer Immunol Immunother 2024; 73:233. [PMID: 39271545 PMCID: PMC11399521 DOI: 10.1007/s00262-024-03820-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 08/27/2024] [Indexed: 09/15/2024]
Abstract
Gastric cancer (GC) is a highly heterogeneous disease with a complex tumor microenvironment (TME) that encompasses multiple cell types including cancer cells, immune cells, stromal cells, and so on. Cancer-associated cells could remodel the TME and influence the progression of GC and therapeutic response. Single-cell RNA sequencing (scRNA-seq), as an emerging technology, has provided unprecedented insights into the complicated biological composition and characteristics of TME at the molecular, cellular, and immunological resolutions, offering a new idea for GC studies. In this review, we discuss the novel findings from scRNA-seq datasets revealing the origin and evolution of GC, and scRNA-seq is a powerful tool for investigating transcriptional dynamics and intratumor heterogeneity (ITH) in GC. Meanwhile, we demonstrate that the vital immune cells within TME, including T cells, B cells, macrophages, and stromal cells, play an important role in the disease progression. Additionally, we also overview that how scRNA-seq facilitates our understanding about the effects on individualized therapy of GC patients. Spatial transcriptomes (ST) have been designed to determine spatial distribution and capture local intercellular communication networks, enabling a further understanding of the relationship between the spatial background of a particular cell and its functions. In summary, scRNA-seq and other single-cell technologies provide a valuable perspective for molecular and pathological disease characteristics and hold promise for advancing basic research and clinical practice in GC.
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Affiliation(s)
- Jiao Xu
- Precision Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road., Xi'an, 710061, Shaanxi, People's Republic of China
| | - Bixin Yu
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road., Xi'an, 710061, Shaanxi, People's Republic of China
| | - Fan Wang
- Phase I Clinical Trial Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China.
| | - Jin Yang
- Precision Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road., Xi'an, 710061, Shaanxi, People's Republic of China.
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road., Xi'an, 710061, Shaanxi, People's Republic of China.
- Phase I Clinical Trial Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China.
- Cancer Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China.
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Oh CR, Kim EJ, Chae H, Park YS, Ryu MH, Kim HD, Kang YK. Prognostic value of mismatch repair deficiency in patients receiving first-line fluoropyrimidine plus platinum for metastatic, recurrent, or unresectable gastric cancer. Gastric Cancer 2024; 27:811-818. [PMID: 38555561 DOI: 10.1007/s10120-024-01483-9] [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: 11/05/2023] [Accepted: 02/17/2024] [Indexed: 04/02/2024]
Abstract
BACKGROUND We examined the impact of mismatch repair (MMR) status on efficacy of first-line fluoropyrimidine plus platinum (FP) chemotherapy in patients with HER2-negative metastatic, recurrent, or unresectable gastric cancer (mGC). METHODS Patients with mGC receiving first-line FP between 2015 and 2018 at Asan Medical Center, Korea, were reviewed. We evaluated the clinical characteristics and the efficacy of chemotherapy according to MMR status in patients with available immunohistochemistry results. RESULTS Of 895 patients, we analyzed 543 with available MMR protein expression results, and deficient MMR (dMMR) was detected in 4.4% (n = 24). Patients with dMMR exhibited a significantly higher median age than those with proficient MMR (pMMR) (64 vs. 58 years, p = 0.044). No signet ring cell carcinoma (SRCC) was detected among dMMR tumors, whereas SRCC was found in 17.5% of pMMR. Objective response rate was 27.3% in dMMR and 34.3% in pMMR (p = 0.556). No difference in progression-free survival was noted between patients with dMMR and pMMR (median, 5.6 vs. 5.8 months, p = 0.266). Patients with dMMR tended to have better overall survival than those with pMMR although this difference was not statistically significant (median, 17.9 vs. 12.2 months, p = 0.183). CONCLUSIONS Efficacy of first-line FP was not different by MMR status in mGC patients.
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Affiliation(s)
- Chung Ryul Oh
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
- Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Eo Jin Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Heejung Chae
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Young Soo Park
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Min-Hee Ryu
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Hyung-Don Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Yoon-Koo Kang
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
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Xu J, Yu B, Wang F, Yang J. Xenograft and organoid models in developing precision medicine for gastric cancer (Review). Int J Oncol 2024; 64:41. [PMID: 38390969 PMCID: PMC10919760 DOI: 10.3892/ijo.2024.5629] [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] [Accepted: 02/08/2024] [Indexed: 02/24/2024] Open
Abstract
Gastric cancer (GC), a highly heterogeneous disease, has diverse histological and molecular subtypes. For precision medicine, well‑characterized models encompassing the full spectrum of subtypes are necessary. Patient‑derived tumor xenografts and organoids serve as important preclinical models in GC research. The main advantage of these models is the retention of phenotypic and genotypic heterogeneity present in parental tumor tissues. Utilizing diverse sequencing techniques and preclinical models for GC research facilitates accuracy in predicting personalized clinical responses to anti‑cancer treatments. The present review summarizes the latest advances of these two preclinical models in GC treatment and drug response assessment.
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Affiliation(s)
- Jiao Xu
- Precision Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Bixin Yu
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Fan Wang
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Jin Yang
- Precision Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
- Phase I Clinical Trial Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
- Cancer Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
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Dal Cero M, Bencivenga M, Liu DHW, Sacco M, Alloggio M, Kerckhoffs KGP, Filippini F, Saragoni L, Iglesias M, Tomezzoli A, Carneiro F, Grabsch HI, Verlato G, Torroni L, Piessen G, Pera M, de Manzoni G. Clinical Features of Gastric Signet Ring Cell Cancer: Results from a Systematic Review and Meta-Analysis. Cancers (Basel) 2023; 15:5191. [PMID: 37958365 PMCID: PMC10647446 DOI: 10.3390/cancers15215191] [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: 09/05/2023] [Revised: 10/17/2023] [Accepted: 10/26/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND Conflicting results about the prognostic relevance of signet ring cell histology in gastric cancer have been reported. We aimed to perform a meta-analysis focusing on the clinicopathological features and prognosis of this subgroup of cancer compared with other histologies. METHODS A systematic literature search in the PubMed database was conducted, including all publications up to 1 October 2021. A meta-analysis comparing the results of the studies was performed. RESULTS A total of 2062 studies referring to gastric cancer with signet ring cell histology were identified, of which 262 studies reported on its relationship with clinical information. Of these, 74 were suitable to be included in the meta-analysis. A slightly lower risk of developing nodal metastases in signet ring cell tumours compared to other histotypes was found (especially to undifferentiated/poorly differentiated/mucinous and mixed histotypes); the lower risk was more evident in early and slightly increased in advanced gastric cancer. Survival tended to be better in early stage signet ring cell cancer compared to other histotypes; no differences were shown in advanced stages, and survival was poorer in metastatic patients. In the subgroup analysis, survival in signet ring cell cancer was slightly worse compared to non-signet ring cell cancer and differentiated/well-to-moderately differentiated adenocarcinoma. CONCLUSIONS Most of the conflicting results in signet ring cell gastric cancer literature could be derived from the lack of standardisation in their classification and the comparison with the different subtypes of gastric cancer. There is a critical need to strive for a standardised classification system for gastric cancer, fostering clarity and coherence in the forthcoming research and clinical applications.
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Affiliation(s)
- Mariagiulia Dal Cero
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Borgo Trento Hospital, Piazzale Stefani 1, 37124 Verona, Italy; (M.D.C.)
- Section of Gastrointestinal Surgery, Hospital Universitario del Mar, Hospital del Mar Medical Research Institute (IMIM), Department of Surgery, Universitat Autònoma de Barcelona, 08003 Barcelona, Spain
| | - Maria Bencivenga
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Borgo Trento Hospital, Piazzale Stefani 1, 37124 Verona, Italy; (M.D.C.)
| | - Drolaiz H. W. Liu
- Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands
- Institute of Clinical Pathology and Molecular Pathology, Kepler University Hospital and Johannes Kepler University, 4021 Linz, Austria
| | - Michele Sacco
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Borgo Trento Hospital, Piazzale Stefani 1, 37124 Verona, Italy; (M.D.C.)
| | - Mariella Alloggio
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Borgo Trento Hospital, Piazzale Stefani 1, 37124 Verona, Italy; (M.D.C.)
| | - Kelly G. P. Kerckhoffs
- Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands
- Department of Pathology, VieCuri Medical Centre, 5912 BL Venlo, The Netherlands
| | - Federica Filippini
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Borgo Trento Hospital, Piazzale Stefani 1, 37124 Verona, Italy; (M.D.C.)
| | - Luca Saragoni
- Pathology Unit, Morgagni-Pierantoni Hospital, 47100 Forlì, Italy
| | - Mar Iglesias
- Department of Pathology, Hospital Universitario del Mar, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain
| | - Anna Tomezzoli
- Department of Pathology, Verona University Hospital, 37134 Verona, Italy
| | - Fátima Carneiro
- Department of Pathology, Medical Faculty of the University of Porto/Centro Hospitalar Universitário São João and Ipatimup/i3S, 4200-319 Porto, Portugal
| | - Heike I. Grabsch
- Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands
- Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St. James’s, University of Leeds, Leeds LS2 9JT, UK
| | - Giuseppe Verlato
- Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, 37126 Verona, Italy
| | - Lorena Torroni
- Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, 37126 Verona, Italy
| | - Guillaume Piessen
- Department of Digestive and Oncological Surgery, Lille University Hospital, 59000 Lille, France
| | - Manuel Pera
- Section of Gastrointestinal Surgery, Hospital Universitario del Mar, Hospital del Mar Medical Research Institute (IMIM), Department of Surgery, Universitat Autònoma de Barcelona, 08003 Barcelona, Spain
| | - Giovanni de Manzoni
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Borgo Trento Hospital, Piazzale Stefani 1, 37124 Verona, Italy; (M.D.C.)
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Zhao W, Jia Y, Sun G, Yang H, Liu L, Qu X, Ding J, Yu H, Xu B, Zhao S, Xing L, Chai J. Single-cell analysis of gastric signet ring cell carcinoma reveals cytological and immune microenvironment features. Nat Commun 2023; 14:2985. [PMID: 37225691 DOI: 10.1038/s41467-023-38426-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Accepted: 05/03/2023] [Indexed: 05/26/2023] Open
Abstract
Gastric signet ring cell carcinoma (GSRC) is a special subtype of gastric cancer (GC) associated with poor prognosis, but an in-depth and systematic study of GSRC is lacking. Here, we perform single-cell RNA sequencing to assess GC samples. We identify signet ring cell carcinoma (SRCC) cells. Microseminoprotein-beta (MSMB) can be used as a marker gene to guide the identification of moderately/poorly differentiated adenocarcinoma and signet ring cell carcinoma (SRCC). The upregulated differentially expressed genes in SRCC cells are mainly enriched in abnormally activated cancer-related signalling pathways and immune response signalling pathways. SRCC cells are also significantly enriched in mitogen-activated protein kinase and oestrogen signalling pathways, which can interact and promote each other in a positive feedback loop. SRCC cells are shown to have lower cell adhesion and higher immune evasion capabilities as well as an immunosuppressive microenvironment, which may be closely associated with the relatively poor prognosis of GSRC. In summary, GSRC exhibits unique cytological characteristics and a unique immune microenvironment, which may be advantageous for accurate diagnosis and treatment.
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Affiliation(s)
- Weizhu Zhao
- Department of Radiation Oncology, Shandong University Cancer Center, Jinan, Shandong, China
- Department of Radialogy Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Department of Oncology, Binzhou People's Hospital Affiliated to Shandong First Medical University, Binzhou, Shandong, China
| | - Yanfei Jia
- Research Center of Basic Medicine, Jinan Central Hospital, Shandong First Medical University, Jinan, Shandong, China
| | - Guangyu Sun
- Department of Oncology, Binzhou People's Hospital Affiliated to Shandong First Medical University, Binzhou, Shandong, China
| | - Haiying Yang
- Department of Cardiology, Binzhou People's Hospital Affiliated to Shandong First Medical University, Binzhou, Shandong, China
| | - Luguang Liu
- Department of Gastroenterological Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Xianlin Qu
- Department of Gastroenterological Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Jishuang Ding
- Department of Gastroenterological Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Hang Yu
- Department of Gastroenterological Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Botao Xu
- Department of Gastroenterological Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Siwei Zhao
- Department of Gastroenterological Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Ligang Xing
- Department of Radiation Oncology, Shandong University Cancer Center, Jinan, Shandong, China.
- Department of Radialogy Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
| | - Jie Chai
- Department of Gastroenterological Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
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10
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Pancancer Analysis of Revealed TDO2 as a Biomarker of Prognosis and Immunotherapy. DISEASE MARKERS 2022; 2022:5447017. [PMID: 36118672 PMCID: PMC9481368 DOI: 10.1155/2022/5447017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 08/27/2022] [Indexed: 12/17/2022]
Abstract
Background Tryptophan 2,3-dioxygenase (TDO) encoded by TDO2, a rate-limiting enzyme in the kynurenine pathway, catabolizes tryptophan to kynurenine, evades immune surveillance, and promotes tumor growth. Although accumulating evidence suggests a crucial role of TDO2 during tumor formation and development, systematic evaluation of TDO2 across human cancers has rarely been reported. Methods To shed more light on the role of TDO2 in human cancer, we explored the expression profiles of TDO2 and identified its prognostic value in pancancer analysis through TCGA, CCLE, and GTEx databases. We further utilized TCGA data to evaluate the association between TDO2 and tumor immunological features, such as mismatch repair (MMR), tumor immune infiltration, immune checkpoint-related genes, tumor mutational burden (TMB), microsatellite instability (MSI), and DNA methyltransferase (DNMT). Results TDO2 exhibited different expression levels in various cancer cell lines. Frequently, TDO2 was detected to be highly expressed in the majority of cancers. In addition, high TDO2 expression was correlated with an unfavorable prognosis for patients in KIRP, LGG, TGCT, and UVM. Moreover, high TDO2 expression level positively correlated with higher immune infiltration, especially dendritic cells. Additionally, there is a close relationship between TDO2 and immune checkpoint-related gene markers, such as LAIR1, CD276, NRP1, CD80, and CD86. Finally, correlation analysis has demonstrated a high-correlation between TDO2 and TMB, MSI, MMR, and DNMT of multiple cancer types. Conclusion Therefore, our results suggest that TDO2 can function as a potential prognostic biomarker due to its role in tumor immunity regulation.
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Mari V, Angerilli V, Munari G, Scarpa M, Bao QR, Pucciarelli S, Fassan M, Spolverato G. Molecular Determinants of Peritoneal Dissemination in Gastric Adenocarcinoma. Dig Dis 2022; 41:49-65. [PMID: 35940137 DOI: 10.1159/000526333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 07/25/2022] [Indexed: 02/02/2023]
Abstract
BACKGROUND Peritoneal dissemination represents a poor prognostic indicator in gastric cancer. Despite a comprehensive molecular characterization of this disease, no peritoneal dissemination-specific signature has been identified, limiting the tailoring of the surgical and oncological treatments. In this review, we outline the available literature focusing on the role of the different molecular pathways involved in the acquisition of peritoneal metastatic dissemination. SUMMARY According to our results, several molecular determinants are associated with peritoneal carcinomatosis and are involved in several cellular and molecular carcinogenetic processes. However, a comprehensive understanding of the complex molecular landscape of gastric carcinosis is still lacking. KEY MESSAGES More efforts should be made toward the integration of molecular and histologic data to perform a risk prediction assessment of peritoneal dissemination based on molecular profiling and histological evaluation.
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Affiliation(s)
- Valentina Mari
- Department of Surgical, General Surgery 3, Oncological and Gastroenterological Sciences (DISCOG), University of Padua, Padua, Italy
| | - Valentina Angerilli
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Giada Munari
- Veneto Institute of Oncology (I.O.V. IRCSS), Padua, Italy
| | - Marco Scarpa
- Department of Surgical, General Surgery 3, Oncological and Gastroenterological Sciences (DISCOG), University of Padua, Padua, Italy
| | - Quoc Riccardo Bao
- Department of Surgical, General Surgery 3, Oncological and Gastroenterological Sciences (DISCOG), University of Padua, Padua, Italy
| | - Salvatore Pucciarelli
- Department of Surgical, General Surgery 3, Oncological and Gastroenterological Sciences (DISCOG), University of Padua, Padua, Italy
| | - Matteo Fassan
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
- Veneto Institute of Oncology (I.O.V. IRCSS), Padua, Italy
| | - Gaya Spolverato
- Department of Surgical, General Surgery 3, Oncological and Gastroenterological Sciences (DISCOG), University of Padua, Padua, Italy
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12
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He Z, Li D, Xu Y, Wang H, Gao J, Zhang Z, Chen K. Prognostic significance of metastatic lymph node ratio in patients with gastric cancer after curative gastrectomy: a single-center retrospective study. Scand J Gastroenterol 2022; 57:832-841. [PMID: 35293268 DOI: 10.1080/00365521.2022.2036807] [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: 11/02/2021] [Revised: 01/26/2022] [Accepted: 01/27/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND The objective of this study was to evaluate the prognostic value of Metastatic lymph node ratio (MLNR) after curative gastrectomy in patients with gastric cancer (GC) and the potential for new indicators to strengthen the current guidelines. METHODS We retrospectively researched 3864 GC patients with curative gastrectomy between February 2011 and February 2016. The following clinical data were collected from the included patients: gender, type of gastrectomy, tumor location, T stage, N stage, ELN, tumor size, age at surgery, perineural invasion, vascular invasion, TNM stage, survival time and survival status. Patients were divided into low-MLNR (L-MLNR), and high-MLNR (H-MLNR) groups based on adjusted the X-tile cutoff-value of 0.25 for MLNR, the survival rates and clinicopathological characteristics of each group were compared. For the assessment of significant associations between clinicopathological characteristics and patients' survival, univariate and multivariate analyses were performed using the Kaplan-Meier method and Cox proportional hazards analysis. The log-rank test was used to examine the statistical significance of differences among different survival curves. Clinicopathological features significantly associated with MLNR were assessed by the Chi-square test and multinomial logistic regression. The discriminative ability was measured by calculating the Bayesian Information Criterion (BIC) values for each category. Assessment of the effect of clinicopathological features on MLNR for predicting prognosis of GC patients used stratum analysis through Kaplan-Meier analysis and Cox proportional risk Analysis. RESULTS Survival analysis indicated that MLNR was negatively associated with overall survival (OS) (p < .001) and was an independent prognostic predictor in 3864 GC patients (p < .001). MLNR had significant prognostic significance in various subgroups with clinicopathological characteristics (gender, type of gastrectomy, tumor location, T stage, N stage, ELN, tumor size, age at surgery, perineural invasion, vascular invasion, and TNM stage) (p < .001). CONCLUSIONS The MLNR may become a new indicator to assess the prognosis of GC patients who underwent curative gastrectomy. The results may have potential clinical implications that should be considered when developing clinical practice guidelines or the design of the future investigation.
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Affiliation(s)
- Zhipeng He
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Dongchang Li
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yunfeng Xu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Haoran Wang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Junpeng Gao
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Zhigong Zhang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Ke Chen
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
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13
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Yuan L, Xu J, Shi Y, Jin Z, Bao Z, Yu P, Wang Y, Xia Y, Qin J, Zhang B, Yao Q. CD3D Is an Independent Prognostic Factor and Correlates With Immune Infiltration in Gastric Cancer. Front Oncol 2022; 12:913670. [PMID: 35719985 PMCID: PMC9198637 DOI: 10.3389/fonc.2022.913670] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 04/27/2022] [Indexed: 12/20/2022] Open
Abstract
The protein encoded by CD3D is part of the T-cell receptor/CD3 complex (TCR/CD3 complex) and is involved in T-cell development and signal transduction. Previous studies have shown that CD3D is associated with prognosis and treatment response in breast, colorectal, and liver cancer. However, the expression and clinical significance of CD3D in gastric cancer are not clear. In this study, we collected 488 gastric cancer tissues and 430 paired adjacent tissues to perform tissue microarrays (TMAs). Then, immunohistochemical staining of CD3D, CD3, CD4, CD8 and PD-L1 was conducted to investigate the expression of CD3D in gastric cancer and the correlation between the expression of CD3D and tumor infiltrating lymphocytes (TILs) and PD-L1. The results showed that CD3D was highly expressed in gastric cancer tissues compared with paracancerous tissues (P<0.000). Univariate and multivariate analyses showed that CD3D was an independent good prognostic factor for gastric cancer (P=0.004, HR=0.677, 95%CI: 0.510-0.898 for univariate analyses; P=0.046, HR=0.687, 95%CI: 0.474-0.994 for multivariate analyses). In addition, CD3D was negatively correlated with the tumor location, Borrmann type and distant metastasis (P=0.012 for tumor location; P=0.007 for Borrmann type; P=0.027 for distant metastasis). In addition, the expression of CD3D was highly positively correlated with the expression of CD3, CD4, CD8, and PD-L1, and the combination of CD3D with CD3, CD4, CD8 and PD-L1 predicted the best prognosis (P=0.043). In summary, CD3D may play an important regulatory role in the tumor immune microenvironment of gastric cancer and may serve as a potential indicator of prognosis and immunotherapy response.
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Affiliation(s)
- Li Yuan
- The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.,Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China.,Zhejiang Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Jingli Xu
- First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yunfu Shi
- First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Zhiyuan Jin
- The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
| | - Zhehan Bao
- First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Pengcheng Yu
- First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yi Wang
- First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yuhang Xia
- First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jiangjiang Qin
- The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.,Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China.,Zhejiang Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Bo Zhang
- Department of Integrated Chinese and Western Medicine, Institute of Basic Medicine and Cancer (IBMC), The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Chinese Academy of Sciences, Hangzhou, China
| | - Qinghua Yao
- Department of Integrated Chinese and Western Medicine, Institute of Basic Medicine and Cancer (IBMC), The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Chinese Academy of Sciences, Hangzhou, China.,Key Laboratory of Traditional Chinese Medicine Oncology, Zhejiang Cancer Hospital, Hangzhou, China.,Key Laboratory of Head and Neck Cancer Translational Research of Zhejiang Province, Hangzhou, China
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14
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Ma J, Meng Y, Zhou X, Guo L, Fu W. The Prognostic Significance and Gene Expression Characteristics of Gastric Signet-Ring Cell Carcinoma: A Study Based on the SEER and TCGA Databases. Front Surg 2022; 9:819018. [PMID: 35372476 PMCID: PMC8967986 DOI: 10.3389/fsurg.2022.819018] [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: 11/20/2021] [Accepted: 02/07/2022] [Indexed: 11/13/2022] Open
Abstract
PurposeThis study is based on the Surveillance, Epidemiology, and End Results (SEER) program to explore the prognostic differences between signet-ring cell carcinoma (SRC) and intestinal-type gastric carcinoma (ITGC). This study is also based on gene sequencing data from The Cancer Genome Atlas (TCGA) to identify unique genetic contributions to the prognostic differences between the two subtypes of gastric cancer.Patients and MethodsThe clinical data were based on the SEER database from 2004 to 2015. Kaplan–Meier (KM) curves were used to compare 5-year overall survival (OS), and Cox regression was used for univariate and multivariate analyses. Gene expression profiles were obtained from TCGA database, and differentially expressed genes (DEGs) were screened. Functional enrichment analysis, protein interaction and survival analysis will be further carried out. Genes of interest were verified by the Human Protein Atlas, immunohistochemistry, and encyclopedia of Cancer Cell Lines (CCLE). The relationship between genes of interest and immune cell infiltration was also analyzed by Tumor Immune Estimation Resource (TIMER).ResultsCompared with ITGC patients, SRC patients were more likely to be female, tended to be younger, and have a greater tumor distribution in the middle and lower stomach (p < 0.01). SRCs showed a significantly better prognosis than ITGCs (p < 0.01) in early gastric cancer (EGC), while the prognosis of SRCs was significantly worse than ITGCs (p < 0.05) in advanced gastric cancer (AGC). A total of 256 DEGs were screened in SRCs compared to ITGCs, and the enrichment analysis and protein interactions revealed that differential genes were mainly related to extracellular matrix organization. Thrombospondin1 (THBS1) and serpin peptidase inhibitor, clade E, member 1 (SERPINE1) are significantly differentially expressed between SRC and ITGC, which has been preliminarily verified by immunohistochemistry and open-source databases. THBS1 and SERPINE1 are also associated with multiple immune cell infiltrates in gastric cancer.ConclusionsThere were significant differences in the clinicopathological features and prognosis between SRC and ITGC. These results suggest that SRC and ITGC may be two distinct types of tumors with different pathogeneses. We found many codifferentially expressed genes and important pathways between SRC and ITGC. THBS1 and SERPINE1 were significantly differentially expressed in the two types of gastric cancer, and may have potentially important functions.
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Affiliation(s)
- Junren Ma
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Yan Meng
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Xin Zhou
- Department of General Surgery, Peking University Third Hospital, Beijing, China
- Peking University Third Hospital Cancer Center, Beijing, China
- *Correspondence: Xin Zhou
| | - Limei Guo
- Department of Pathology, Peking University Third Hospital, Beijing, China
- Limei Guo
| | - Wei Fu
- Department of General Surgery, Peking University Third Hospital, Beijing, China
- Peking University Third Hospital Cancer Center, Beijing, China
- Wei Fu
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15
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Anatomic Subsites and Prognosis of Gastric Signet Ring Cell Carcinoma: A SEER Population-Based 1 : 1 Propensity-Matched Study. BIOMED RESEARCH INTERNATIONAL 2022; 2022:1565207. [PMID: 35141330 PMCID: PMC8818421 DOI: 10.1155/2022/1565207] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 08/11/2021] [Accepted: 01/03/2022] [Indexed: 12/12/2022]
Abstract
Background. The dismal prognosis of gastric signet ring cell carcinoma (GSRC) is a global problem. The current study is conducted to comprehensively evaluate clinicopathological features and survival outcomes in GSRC patients stratified by anatomic subsites. Then, predictive nomograms are constructed and validated to improve the effectiveness of personalized management. Method. The patients diagnosed with GSRC were recruited from the online SEER database. The influence of anatomic subsites on overall survival (OS) and cancer-specific survival (CSS) was evaluated using multivariate Cox regression and Kaplan-Meier analysis. Then, we employed propensity score matching (PSM) technique to decrease selection bias and balance patients’ epidemiological factors. Predictive nomograms were constructed and validated. Sensitivity analysis was performed to validate the conclusion. Results. Multivariate Cox regression demonstrated that the patients with overlapping gastric cancer (OGC) suffered the highest mortality risk for OS (HR, 1.29; 95% CI, 1.23-1.36;
) and CSS (HR, 1.33; 95% CI, 1.28-1.37;
). Age, TNM stage, tumor localization, tumor size, surgery, and chemotherapy presented a highly significant relationship with OS and CSS. Following subgroup and PSM analysis, OGC patients were confirmed to have the worst OS and CSS. Then, nomograms predicting 6-month, 12-month, and 36-month survival were constructed. The area under the curve (AUC) value in ROC was 0.775 (95% CI, 0.761-0.793) for 6-month survival, 0.789 (95% CI, 0.776-0.801) for 12-month survival, and 0.780 (95% CI, 0.765-0.793) for 36-month survival in the OS group, while in the CSS group, it was 0.771 (95% CI, 0.758-0.790) for 6-month survival, 0.781 (95% CI, 0.770-0.799) for 12-month survival, and 0.773 (95% CI, 0.762-0.790) for 36-month survival. Conclusion. We identified anatomic subsites as a predictor of survival in those with GSRC. Patients with OGC suffered the highest mortality risk. The proposed nomograms allowed a relatively accurate survival prediction for GSRC patients.
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16
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Takiguchi K, Shoda K, Nakayama T, Takahashi K, Saito R, Yamamoto A, Furuya S, Akaike H, Hosomura N, Kawaguchi Y, Amemiya H, Kawaida H, Inoue S, Kono H, Konishi H, Otsuji E, Ichikawa D. Soluble podoplanin as a biomarker in diffuse‑type gastric cancer. Oncol Rep 2022; 47:51. [PMID: 35029281 DOI: 10.3892/or.2022.8262] [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: 09/02/2021] [Accepted: 11/30/2021] [Indexed: 12/24/2022] Open
Abstract
Diffuse‑type gastric cancer, also known as scirrhous gastric cancer, is characterized by a larger number of stromal cells, referred to as cancer‑associated fibroblasts (CAFs), than the number of cancer cells in the tissue. The present study focused on CAFs in gastric cancer and examined their potential as a blood biomarker. A total of 46 and 84 patients with gastric cancer were respectively included in a development and an independent validation cohort to assess the clinicopathological characteristics of plasma podoplanin (PDPN) levels. The prognostic impact of plasma PDPN was also investigated in the validation cohort. The cut‑off value of the plasma‑PDPN concentration was set to the median plasma PDPN concentration in the development cohort that was then divided into the high‑PDPN and low‑PDPN groups. The high‑PDPN group tended to have more diffuse‑type disease (P=0.079), which was further confirmed through logistic regression analysis (P=0.008). Kaplan‑Meier survival estimates indicated that the recurrence‑free survival rate was significantly lower in the high‑PDPN group (P=0.029). In conclusion, plasma soluble PDPN was demonstrated to be a marker for diffuse gastric cancer and may reflect the prognosis of this disease.
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Affiliation(s)
- Koichi Takiguchi
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409‑3898, Japan
| | - Katsutoshi Shoda
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409‑3898, Japan
| | - Takashi Nakayama
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409‑3898, Japan
| | - Kazunori Takahashi
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409‑3898, Japan
| | - Ryo Saito
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409‑3898, Japan
| | - Atsushi Yamamoto
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409‑3898, Japan
| | - Shinji Furuya
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409‑3898, Japan
| | - Hidenori Akaike
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409‑3898, Japan
| | - Naohiro Hosomura
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409‑3898, Japan
| | - Yoshihiko Kawaguchi
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409‑3898, Japan
| | - Hidetake Amemiya
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409‑3898, Japan
| | - Hiromichi Kawaida
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409‑3898, Japan
| | - Shingo Inoue
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409‑3898, Japan
| | - Hiroshi Kono
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409‑3898, Japan
| | - Hirotaka Konishi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602‑8566, Japan
| | - Eigo Otsuji
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602‑8566, Japan
| | - Daisuke Ichikawa
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409‑3898, Japan
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17
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Teng QL, Yang XR, Wen S, Dai ZH, Wang HL, Liu TQ, Wang L, Fan B, Liu ZY. Immunohistochemical analysis of PD-L1 and tumor-infiltrating immune cells expression in the tumor microenvironment of primary signet ring cell carcinoma of the prostate. Asian J Androl 2022; 24:525-532. [PMID: 35042311 PMCID: PMC9491031 DOI: 10.4103/aja202186] [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] [Indexed: 11/30/2022] Open
Abstract
Primary signet ring cell carcinoma (SRCC) of the prostate is a rare neoplasm. However, its potential tumorigenic mechanism, clinicopathological features, and prognostic outcome have not been systematically described. To determine the pathogenic mechanism, we detected distributions of programmed cell death-ligand 1 (PD-L1), programmed death 1 (PD-1), and cellular components in the tumor microenvironment, including tumor-infiltrating lymphocytes (CD4 and CD8), tumor-associated macrophages (TAMs; CD163 and CD68), and tumor-associated fibroblasts (vimentin and alpha-smooth muscle actin [α-SMA]), in tumor tissues from four patients with primary prostatic SRCC compared with corresponding adjacent tissues and tumor tissues from 30 patients with prostate adenocarcinoma (PCa) by immunohistochemical staining. We found higher expression of PD-L1, CD163, and CD68 in primary SRCC specimens than that in both corresponding adjacent nontumor specimens and PCa specimens with different Gleason scores, indicating that TAMs may participate in the malignant biological behavior of primary SRCC of the prostate. For further analysis, we searched electronic journal databases and Surveillance, Epidemiology, and End Results (SEER) to identify 200 eligible patients including our four cases. According to Kaplan–Meier survival curve analysis, patients <68 years old, with radical prostatectomy (RP), Gleason score of 7–8, and lower clinical stage had longer overall survival (OS). Moreover, Cox multivariate analysis indicated that race (hazard ratio [HR] = 1.422), surgical approach (HR = 1.654), and Gleason score (HR = 2.162) were independent prognostic factors for OS. Therefore, primary SRCC of the prostate represents a distinct and aggressive subtype of prostate cancer associated with a higher distribution of PD-L1 and TAMs, which warrants further clinical investigation.
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Affiliation(s)
- Qi-Liang Teng
- Department of Urology, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China
| | - Xin-Rui Yang
- Department of Clinical Imaging, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China
| | - Shuang Wen
- Department of Pathology, Dalian Friendship Hospital, Dalian 116001, China
| | - Zhi-Hong Dai
- Department of Urology, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China
| | - Hong-Long Wang
- Department of Pathology, Dalian Friendship Hospital, Dalian 116001, China
| | - Tian-Qing Liu
- Department of Pathology, Dalian Friendship Hospital, Dalian 116001, China
| | - Liang Wang
- Department of Urology, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China
| | - Bo Fan
- Department of Urology, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China
| | - Zhi-Yu Liu
- Department of Urology, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China
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18
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Li G, Ma S, Wu Q, Kong D, Yang Z, Gu Z, Feng L, Zhang K, Cheng S, Tian Y, Zhang W. Establishment of gastric signet ring cell carcinoma organoid for the therapeutic drug testing. Cell Death Discov 2022; 8:6. [PMID: 35013129 PMCID: PMC8748936 DOI: 10.1038/s41420-021-00803-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 11/29/2021] [Accepted: 12/14/2021] [Indexed: 12/30/2022] Open
Abstract
Signet ring cell carcinoma (SRCC) has specific oncogenesis and phenotypic and treatment resistance heterogeneity. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. Tumor organoids have recently emerged as an ideal model for drug testing and screening. Here, we report gastric organoids established from tumor tissues comprising four SRCCs and eight non-SRCCs. Tumor organoids demonstrated different growth characteristics and morphologies. Changes in the original tumor genome were maintained during long-term culture from whole-exome sequencing (WES) analysis. Immunohistochemistry and H&E staining showed that the tissue characteristics of the primary tumor could be recapitulated. In addition, organoid lines successfully formed tumors in immunodeficient mice and maintained tumorigenic character. Different responses to 5-fluorouracil, oxaliplatin, docetaxel and irinotecan treatment were observed in SRCC and non-SRCC organoids. These results demonstrate that gastric organoid drug models, including SRCC, were highly similar to the original tumors in phenotypic and genotypic profiling and could be as living biomarkers for drug response testing.
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Affiliation(s)
- Guoliang Li
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China
| | - Shuai Ma
- 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, 100021, Beijing, China
| | - Quanyou Wu
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China
| | - Defeng Kong
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China
| | - Zhenrong Yang
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China
| | - Zhaoru Gu
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China
| | - Lin Feng
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China
| | - Kaitai Zhang
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China
| | - Shujun Cheng
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China.
| | - Yantao 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, 100021, Beijing, China.
| | - Wen Zhang
- Department of Immunology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China.
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19
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Wang Y, Shi T, Wang X, Hu J, Yu L, Liu Q, Wu N, Liu B, Wei J. FGFR2 alteration as a potential therapeutic target in poorly cohesive gastric carcinoma. J Transl Med 2021; 19:401. [PMID: 34551773 PMCID: PMC8459493 DOI: 10.1186/s12967-021-03079-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 09/13/2021] [Indexed: 12/24/2022] Open
Abstract
Background Poorly cohesive (PC) is a unique histologic subtype of gastric cancer (GC), with an increasing incidence in recent years. However, the molecular characteristics and therapeutic targets of PC GC are not yet well studied and there are no effective therapies for these patients. Methods Formalin fixed paraffin embedded (FFPE) samples of 556 GC patients, including 64 PC GC, were collected for next-generation sequencing (NGS). Clinical characteristics and genomic profiling were analyzed. FGFR2 expression was detected by quantitative real time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). FGFR2 inhibitors response was studied in vitro. Results Among 556 GC patients, PC GC patients were younger (P = 0.004), had lower tumor mutation burden (TMB-L) (P = 0.001) than non-PC GC. The top 10 most frequently mutated genes in PC GC were TP53 (48%), CDH1 (31%), ARID1A (14%), FGFR2 (14%), ERBB2 (9%), CDKN2A (9%), FGF3 (8%), LRP1B (9%), FGF19 (8%) and FGF4 (8%). Noticeably, FGFR2 is more frequently mutated than non-PC GC (14% vs. 6%, P = 0.037), including copy number variants (CNVs, 12.5%) and gene rearrangements (3.1%, FGFR2/VTI1A and FGFR2/TACC2). Former studies have confirmed that gain of copy number could increase FGFR2 expression and sensitivity to FGFR2 inhibitors in GC. However, no research has verified the function of FGFR2 rearrangements in GC. Our results showed that cell lines of GC transfected with TACC2-FGFR2 fusion had increased mRNA and protein expression of FGFR2, and were more sensitive to FGFR2 inhibitors. FGFR2 inhibitors might be a new therapeutic target for PC GC. In addition, we found patients of PC GC harboring gene rearrangements (n = 9) had poorer overall survival (OS) in comparison with patients without any gene rearrangement (n = 19) (16.0 months vs 21.0 months, P = 0.043). Gene rearrangement might be an adverse prognostic factor for PC GC patients. Conclusions FGFR2 alterations were recurrent in PC GC and FGFR2 inhibitors might be a new therapeutic target for PC GC. Supplementary Information The online version contains supplementary material available at 10.1186/s12967-021-03079-8.
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Affiliation(s)
- Yue Wang
- The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School & Clinical Cancer Institute of Nanjing University, No. 321, Zhongshan Road, Nanjing, 210008, China
| | - Tao Shi
- The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School & Clinical Cancer Institute of Nanjing University, No. 321, Zhongshan Road, Nanjing, 210008, China
| | - Xuan Wang
- The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, No. 321, Zhongshan Road, Nanjing, 210008, China
| | - Jinwei Hu
- OrigiMed, No. 115, Xinjun Ring Road, Shanghai, 201114, China
| | - Lixia Yu
- The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School & Clinical Cancer Institute of Nanjing University, No. 321, Zhongshan Road, Nanjing, 210008, China
| | - Qin Liu
- The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School & Clinical Cancer Institute of Nanjing University, No. 321, Zhongshan Road, Nanjing, 210008, China
| | - Nandie Wu
- The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School & Clinical Cancer Institute of Nanjing University, No. 321, Zhongshan Road, Nanjing, 210008, China
| | - Baorui Liu
- The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School & Clinical Cancer Institute of Nanjing University, No. 321, Zhongshan Road, Nanjing, 210008, China
| | - Jia Wei
- The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School & Clinical Cancer Institute of Nanjing University, No. 321, Zhongshan Road, Nanjing, 210008, China.
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20
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Zhao S, Lv L, Zheng K, Tian Y, Zheng JC, Jiang CG. Prognosis and Biological Behavior of Gastric Signet-Ring Cell Carcinoma Better or Worse: A Meta-Analysis. Front Oncol 2021; 11:603070. [PMID: 34277391 PMCID: PMC8278333 DOI: 10.3389/fonc.2021.603070] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Accepted: 06/11/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND The clinical pathology of gastric signet-ring cell carcinoma (SRC) is still unclear. This meta-analysis was performed to evaluate the difference in biological behavior and prognosis between SRC and non-signet ring cell carcinoma (NSRC). METHODS A total of 58 eligible studies were analyzed using RevMan and other auxiliary software. Biological behaviors were compared based on odds ratio (OR) and mean difference (MD). Hazards ratio (HR) was calculated for prognosis based on Kaplan-Meier curves. RESULTS Totally, 28,946 SRC patients were compared with 81,917 NSRC patients. Compared with NSRC patients, lower male: female ratio (OR = 0.53, P < 0.01), younger age (MD = -4.89, P < 0.01), more middle location (OR = 1.64, P < 0.01), more depressed type at early stage (OR = 1.31, P < 0.05), higher incidence of Borrmann type IV (OR = 1.96, P < 0.01), less lymph node metastasis at early stage (OR = 0.78, P < 0.05), better prognosis at early stage (HR = 0.59, P < 0.01), and worse prognosis at advanced stage (HR = 1.19, P < 0.01) were associated with SRC patients. CONCLUSION The prognosis of SRC at early stage is better than other types of gastric cancer, while that of SRC at advanced stage is relatively poorer.
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Affiliation(s)
- Shuai Zhao
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Ling Lv
- Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Kai Zheng
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Yu Tian
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Jian-Chun Zheng
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Cheng-Gang Jiang
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China
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21
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Huo X, Xiao X, Zhang S, Du X, Li C, Bai Z, Chen Z. Characterization and clinical evaluation of microsatellite instability and loss of heterozygosity in tumor-related genes in gastric cancer. Oncol Lett 2021; 21:430. [PMID: 33868468 PMCID: PMC8045158 DOI: 10.3892/ol.2021.12691] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 02/10/2021] [Indexed: 12/24/2022] Open
Abstract
Microsatellite instability (MSI) detection is widely used in the diagnosis and prognosis evaluation of colorectal cancer. However, for gastric cancer (GC), there is no standard panel of microsatellites (MSs) used in clinical guidance. The present study aimed to identify useful predictors of the clinical features and for the prognosis of GC, based on an investigation of MSI and loss of heterozygosity (LOH) in tumor-related genes. First, from 20 tumor-related genes which were proven to be important to the development of GC, 91 MSs were identified, and PCR amplification, short tandem repeat scanning analysis and TA clone sequencing were used to analyze MSI and LOH in the first set of 90 GC samples. Subsequently, the same method was used to detect the MSI/LOH of the optimized loci in the second set of 136 GC samples. MSI/LOH in the mismatch repair genes was highly consistent with that in oncogenes and tumor suppressor genes, respectively. The length of the core sequence was a main factor for the MSI/LOH rate. The MSI of 12 single loci was significantly associated with lymph node metastasis. The MSI in TP53-1 and the LOH in MGMT-10 were significantly associated with early stages of tumor infiltration depth. The LOH in MGMT-10, PTN-2 and MCC-17 was significantly associated with TNM stage. The LOH in TP53-1 and ERBB2-12 was associated with adenocarcinoma. The MSI/LOH in 6 single loci of 5 tumor-related genes was associated with poor prognosis of GC. The present study demonstrated that the MSI/LOH of loci in tumor-associated genes was associated with 4 clinicopathological characteristics and outcomes of GC. These results may provide potential specific biomarkers for the clinical prediction and treatment of GC.
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Affiliation(s)
- Xueyun Huo
- School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P.R. China
- Tumor Model Laboratory, Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, P.R. China
| | - Xiaoqin Xiao
- School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P.R. China
- Tumor Model Laboratory, Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, P.R. China
| | - Shuangyue Zhang
- School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P.R. China
- Tumor Model Laboratory, Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, P.R. China
| | - Xiaoyan Du
- School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P.R. China
- Tumor Model Laboratory, Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, P.R. China
| | - Changlong Li
- School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P.R. China
- Tumor Model Laboratory, Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, P.R. China
| | - Zhigang Bai
- Tumor Model Laboratory, Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, P.R. China
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China
- Department of General Surgery, National Clinical Research Center for Digestive Diseases, Beijing 100050, P.R. China
| | - Zhenwen Chen
- School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P.R. China
- Tumor Model Laboratory, Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, P.R. China
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22
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Díaz Del Arco C, Ortega Medina L, Estrada Muñoz L, García Gómez de Las Heras S, Fernández Aceñero MJ. Is there still a place for conventional histopathology in the age of molecular medicine? Laurén classification, inflammatory infiltration and other current topics in gastric cancer diagnosis and prognosis. Histol Histopathol 2021; 36:587-613. [PMID: 33565601 DOI: 10.14670/hh-18-309] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Gastric cancer (GC) is the fifth most common cancer and the third cause of cancer-related deaths worldwide. In western countries, more than half of GC patients are diagnosed at advanced stages and 5-year survival rates range between 20-30%. The only curative treatment is surgery, and despite recent advances in oncological therapies, GC prognosis is still poor. The main prognostic tool for patient categorization and treatment selection is the TNM classification, but its limitations are being increasingly recognized. Early recurrences may occur in early-stage disease, and patients at the same stage show heterogeneous outcomes. Thus, there is a need to improve GC stratification and to identify new prognostic factors, which may allow us to select drug-susceptible populations, refine patient grouping for clinical trials and discover new therapeutic targets. Molecular classifications have been developed, but they have not been translated to the clinical practice. On the other hand, histological assessment is cheap and widely available, and it is still a mainstay in the era of molecular medicine. Furthermore, histological features are acquiring new roles as reflectors of the genotype-phenotype correlation, and their potential impact on patient management is currently being analyzed. The aim of this literature review is to provide a modern overview of the histological assessment of GC. In this study, we discuss recent topics on the histological diagnosis of GC, focusing on the current role of Laurén classification and the potential value of new histological features in GC, such as inflammatory infiltration and tumor budding.
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Affiliation(s)
- Cristina Díaz Del Arco
- Department of Surgical Pathology, Hospital Clínico San Carlos, Madrid, Spain.
- Complutense University of Madrid, Madrid, Spain
| | - Luis Ortega Medina
- Complutense University of Madrid, Madrid, Spain
- Department of Surgical Pathology, Hospital Clínico San Carlos, Madrid, Spain
| | | | | | - Mª Jesús Fernández Aceñero
- Complutense University of Madrid, Madrid, Spain
- Department of Surgical Pathology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
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23
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Campbell DJ, Isch EL, Kozak GM, Yeo CJ. Primary Pancreatic Signet Ring Cell Carcinoma: A Case Report and Review of the Literature. J Pancreat Cancer 2021; 7:1-7. [PMID: 33569523 PMCID: PMC7869882 DOI: 10.1089/pancan.2020.0013] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/22/2020] [Indexed: 11/12/2022] Open
Abstract
Background: Primary pancreatic signet ring cell carcinoma (PPSRCC) is a rare (<1%) poorly reported histopathological variant of pancreatic cancer with ill-defined treatment guidelines. Herein, we describe a case of nonmetastatic PPSRCC in a 45-year-old female. Presentation: A 45-year-old female presented with 3 weeks of abdominal pain radiating to her back. Other pertinent positives included a 20-pound (9.1-kilogram) weight loss and jaundice, with a known 30-pack-year smoking history. CT scan revealed a 4.6 × 3.6 cm hypoattenuating mass in the head of the pancreas (HOP) with dilatation of the common bile duct. Total bilirubin at presentation was elevated, and a biliary stent was placed endoscopically. Subsequent endoscopic ultrasonography revealed a periampullary ulcerated mass involving the HOP and second portion of the duodenum, with pathology revealing poorly differentiated adenocarcinoma with mucinous background and focal signet ring cells. A classic pancreatoduodenectomy (Whipple procedure) was performed. Final pathology revealed a poorly differentiated (G3) pT3/pN2/pM0 PPSRCC with 11 of 16 positive specimen lymph nodes. The tumor had evidence of both KRAS and TP53 mutations and expressed an MUC1+/MUC2-/MUC5AC+ immunophenotype. Medical oncology recommended a 6-month course of adjuvant modified-dose FOLFIRINOX therapy. Conclusion: This report highlights the need for further research into the pathogenesis of gastrointestinal signet ring cell carcinoma to identify and study therapeutic targets that can eventually be translated to PPSRCC treatment. Given the paucity of PPSRCC, adjuvant therapy candidates follow the current literature on more common pancreatic cancer subtypes to guide treatment.
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Affiliation(s)
- Daniel J Campbell
- Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Emily L Isch
- Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Geoffrey M Kozak
- Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Charles J Yeo
- Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
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