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Shilai Z, Shaozhou M, Linlin W, Hua C, Weiwei P, Ziya L, Wenming Q, Zhi Y, Hai L, Guoyou X. Predictive significance of 18F-FDG PET/CT metabolic parameters for the expression level of HER2 in gastric cancer. Front Oncol 2025; 15:1580166. [PMID: 40276059 PMCID: PMC12018366 DOI: 10.3389/fonc.2025.1580166] [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: 02/23/2025] [Accepted: 03/21/2025] [Indexed: 04/26/2025] Open
Abstract
Objective To investigate the predictive value of pertinent metabolic parameters of 18F-FDG PET/CT in relation to the expression level of human epidermal growth factor receptor 2 (HER2) in patients with gastric cancer. Materials and methods The data was retrospectively acquired from 105 patients who had been pathologically diagnosed gastric cancer prior to treatment at our institution, including clinical data, laboratory test results, histological information, 18F-FDG PET/CT metabolic parameters (including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), peak standardized uptake value (SUVpeak), SUVmax normalized by lean body mass (SULmax), SUVmean normalized by lean body mass (SULmean), SUVpeak normalized by lean body mass (SULpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)), and HER2 expression level, from January 2018 to December 2022. The correlation between 18F-FDG PET/CT metabolic parameters and HER2 expression level was examined, and the predictive value of these measures for HER2 expression level was investigated. Results Among the 105 patients, 27 exhibited positive HER2 expression, while 78 demonstrated negative HER2 expression. Significant differences in MTV and TLG between patients exhibiting positive and negative HER2 expression (P < 0.05). The best cut-off values for MTV and TLG were 20.3 cm³ and 72.3 g, yielding accuracy rates of 90.2% and 89.0% for predicting positive HER2 expression, respectively. Our further grouped study shows that in the gastric adenocarcinoma and Lauren classification groups, MTV was significantly negatively correlated with HER2 positivity. Notably, in mixed tumors, the AUC value reached as high as 0.85. Conclusions The negative correlations between MTV/TLG and HER2 status demonstrated that HER2-positive tumors are associated with reduced metabolic burden, providing imaging biomarkers for clinical prognostic assessment. Notably, subgroup analysis in gastric adenocarcinoma and Lauren classification subgroups revealed significant negative associations between MTV and HER2 positivity, highlighting MTV's potential utility in predicting HER2 expression across histological subtypes of gastric cancer and supporting its role in precision oncology.
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Affiliation(s)
- Zhang Shilai
- Department of Nuclear Medicine, Guangxi Key Clinical Specialty (Department of Nuclear Medicine), Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Mo Shaozhou
- Department of Nuclear Medicine, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China
| | - Wei Linlin
- Department of Nuclear Medicine, Guangxi Key Clinical Specialty (Department of Nuclear Medicine), Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Chai Hua
- Department of Nuclear Medicine, Guangxi Key Clinical Specialty (Department of Nuclear Medicine), Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Pu Weiwei
- Department of Nuclear Medicine, Guangxi Key Clinical Specialty (Department of Nuclear Medicine), Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Liu Ziya
- Department of Nuclear Medicine, Guangxi Key Clinical Specialty (Department of Nuclear Medicine), Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Qiu Wenming
- Department of Nuclear Medicine, Guangxi Key Clinical Specialty (Department of Nuclear Medicine), Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Yang Zhi
- Department of Nuclear Medicine, Guangxi Key Clinical Specialty (Department of Nuclear Medicine), Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Liao Hai
- Department of Nuclear Medicine, Guangxi Key Clinical Specialty (Department of Nuclear Medicine), Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Xiao Guoyou
- Department of Nuclear Medicine, Guangxi Key Clinical Specialty (Department of Nuclear Medicine), Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
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Zhang J, Wang G, Liu J, Tang F, Wang S, Li Y. ITGA4 as a potential prognostic and immunotherapeutic biomarker in human cancer and its clinical significance in gastric cancer: an integrated analysis and validation. Front Oncol 2025; 15:1513622. [PMID: 40012546 PMCID: PMC11860100 DOI: 10.3389/fonc.2025.1513622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 01/27/2025] [Indexed: 02/28/2025] Open
Abstract
Background Integrin Subunit Alpha 4 (ITGA4), a member of the integrin protein family, is involved in the progression of malignant tumors. However, its role across different cancer types is not well understood. Methods Utilizing multi-omics data, we comprehensively evaluated ITGA4's expression, clinical relevance, diagnostic and prognostic value, functions, mutations, and methylation status, along with its impact on immunity, mismatch repair (MMR), heterogeneity, stemness, immunotherapy responsiveness, and drug resistance in pan-cancer, with partial validation in gastric cancer (GC) using transcriptomic analysis, single-cell data, western blot (WB), wound-healing assay, flow cytometry and immunohistochemistry (IHC). We further investigated its correlation with clinicopathology and serological markers on tissues from 80 GC patients. Results ITGA4 expression was generally low in normal tissues but varied significantly across tumor types, with higher levels in advanced stages and grades. It demonstrated diagnostic value in 20 cancer types and effectively predicted 1-, 3-, and 5-year survival rates as part of a prognostic model. ITGA4 played roles in cell adhesion, migration, immune regulation, and pathways like PI3K-Akt and TSC-mTOR. It showed alterations in 22 cancer types, with methylation at 9 sites inhibiting its expression. ITGA4 positively correlated with immune cell infiltration, immune regulatory genes, chemokines, and might reduce microsatellite instability (MSI) and tumor mutation burden (TMB) by promoting MMR gene expression. It could also predict immunotherapy efficacy and chemotherapy sensitivity. In GC, high ITGA4 expression was related to poor prognosis, promoted tumor proliferation and migration, and enhanced immune cell infiltration. ITGA4 expression was higher in GC cells and tissues than normal ones. Its downregulation inhibited GC cell migration and promoted apoptosis. Moreover, ITGA4 was correlated with N stage, pathological stage, neural and vascular invasion, serum levels of Ki-67, immune cells, CRP and CA125. Conclusion ITGA4 is a potential biomarker and therapeutic target to enhance cancer treatment and improve patient outcomes.
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Affiliation(s)
- Jiaxing Zhang
- The Second Hospital and Clinical Medical School, Lanzhou University, Lanzhou, China
- Digestive System Tumor Prevention and Treatment and Translational Medicine Engineering Innovation Center of Lanzhou University, Lanzhou University, Lanzhou, China
| | - Gang Wang
- School of Basic Medical Sciences of Lanzhou University, Lanzhou University, Lanzhou, China
| | - Jie Liu
- Ecosystem Change and Population Health Research Group, School of Public Health and Social Work, The Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia
| | - Futian Tang
- Digestive System Tumor Prevention and Treatment and Translational Medicine Engineering Innovation Center of Lanzhou University, Lanzhou University, Lanzhou, China
| | - Song Wang
- The Second Hospital and Clinical Medical School, Lanzhou University, Lanzhou, China
| | - Yumin Li
- The Second Hospital and Clinical Medical School, Lanzhou University, Lanzhou, China
- Digestive System Tumor Prevention and Treatment and Translational Medicine Engineering Innovation Center of Lanzhou University, Lanzhou University, Lanzhou, China
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Chen HZ, Zeng YY, Cai GX, Gu WD, Yang Y. Differential analysis of serum immunology and gut microbiota in patients with gastrointestinal diseases. Front Microbiol 2024; 15:1323842. [PMID: 38751718 PMCID: PMC11094713 DOI: 10.3389/fmicb.2024.1323842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 04/05/2024] [Indexed: 05/18/2024] Open
Abstract
Objective Gastric and intestinal diseases possess distinct characteristics although they are interconnected. The primary objective of this study was to investigate the pathogenesis of gastrointestinal diseases through different analyses of clinical characteristics, serum immunology, and gut microbiota in patients with gastrointestinal diseases. Methods We collected serum samples from 89 patients with gastrointestinal diseases and 9 healthy controls for immunological assessment, stool samples for DNA extraction, library construction, sequencing, as well as clinical data for subsequent analysis. Results Regarding clinical characteristics, there were significant differences between the disease group and the healthy control (HC) group, particularly in terms of age, cancer antigen 125 (CA125), cancer antigen 199 (CA199), alpha-fetoprotein (AFP), total bilirubin (TBIL) and indirect bilirubin (IBIL). The intestinal disease (ID) group exhibited the highest IL-6 level, which significantly differed from the stomach disease (SD) group (p < 0.05). In comparing the HC with the ID groups, significant differences in abundance were detected across 46 species. The HC group displayed a greater abundance of Clostridiales, Clostridia, Firmicutes, Bifidobacterium, Bifidobacteriaceae, Bifidobacteriales, Actinobacteria, Veillonellaceae, Longum, Copri, Megamonas and Callidus than other species. Similarly, when comparing the HC with the SD groups, significant differences in abundance were identified among 49 species, with only one species that the Lachnospiraceae in the HC group exhibited a higher abundance than others. Furthermore, certain clinical characteristics, such as CA125, CA199, glucose (Glu), creatine kinase-MB (CKMB) and interleukin-22 (IL-22), displayed positive correlations with enriched gut species in the ID and SD groups, while exhibiting a negative correlation with the HC group. Conclusion The disturbance in human gut microbiota is intimately associated with the development and progression of gastrointestinal diseases. Moreover, the gut microbiota in the HC group was found more diverse than that in the ID and SD groups, and there were significant differences in microbial species among the three groups at different classification levels. Notably, a correlation was identified between specific clinical characteristics (e.g., CA125, CA199, Glu, CKMB and IL-22) and gut microbiota among patients with gastrointestinal diseases.
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Affiliation(s)
- Huan Zhu Chen
- Biochemistry Teaching and Research Office of the Basic Department of the Medical College of Jiaying University, Meizhou, China
| | - Yu Yang Zeng
- Biochemistry Teaching and Research Office of the Basic Department of the Medical College of Jiaying University, Meizhou, China
| | - Guo Xiong Cai
- Laboratory Department of the Affiliated Hospital of the Medical College of Jiaying University, Meizhou, China
| | - Wei Dan Gu
- Laboratory Department of the Affiliated Hospital of the Medical College of Jiaying University, Meizhou, China
| | - YaLi Yang
- Biochemistry Teaching and Research Office of the Basic Department of the Medical College of Jiaying University, Meizhou, China
- Guangdong Provincial Key Laboratory of Conservation and Precision Utilization of Characteristic Agricultural Resources in Mountainous Areas, Meizhou, China
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Shen Y, Li Y, Wang Z, Xu W, Wang W, Chen X. The prognostic value of FAR and a novel FAR-CA125 score in resectable gastric signet ring cell carcinoma patients. J Cancer Res Clin Oncol 2023; 149:9597-9608. [PMID: 37222811 DOI: 10.1007/s00432-023-04870-4] [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: 04/12/2023] [Accepted: 05/19/2023] [Indexed: 05/25/2023]
Abstract
BACKGROUND The fibrinogen to albumin ratio (FAR) is increasingly regarded as a potential biomarker for predicting prognosis in variety of malignant tumors, but not in gastric signet ring cell carcinoma (GSRC). This study seeks to examine the prognostic value of the FAR and explore a novel FAR-CA125 score (FCS) in resectable GSRC patients. METHODS A retrospective cohort was conducted including 330 GSRC patients who underwent curative resection. Kaplan-Meier (K-M) and Cox regression were used to analysis the prognostic value of FAR and FCS. And a predictive nomogram model was developed. RESULTS The optimal cut-off values for CA125 and FAR were 9.88 and 0.0697, respectively, according to the receiver operating characteristic curve (ROC). Th area under the ROC curve of FCS is higher than CA125 and FAR. 330 patients were grouped into three groups according to the FCS. High FCS was related to males, anemia, tumor size, TNM stage, lymph node metastasis, tumor invasion depth, SII, and pathological subtypes. K-M analysis showed that high FCS and FAR were associated with poor survival. In the multivariate analysis, FCS, TNM stage, and SII were independent prognostic factors for poor OS in resectable GSRC patients. And the predictive accuracy of clinical nomogram contained FCS was better than TNM stage. CONCLUSION This study indicated that the FCS is a prognostic, and effective biomarker for patients with surgically resectable GSRC. Such developed FCS-based nomogram could be effective tools to assist the clinicians to determine the treatment strategy.
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Affiliation(s)
- Yimin Shen
- The Second School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Yuanyuan Li
- The Second School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Zhou Wang
- The Second School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Wei Xu
- The Second School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Wenjie Wang
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China
| | - Xiao Chen
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China.
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Zhang Z, Miao L, Wang S, Zhao Y, Xie Y, Yun H, Ren Z, Wang G, Teng M, Li Y. Study on the expression of c-Met in gastric cancer and its correlation with preoperative serum tumor markers and prognosis. World J Surg Oncol 2022; 20:204. [PMID: 35710379 PMCID: PMC9202172 DOI: 10.1186/s12957-022-02659-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 05/28/2022] [Indexed: 12/04/2022] Open
Abstract
Background Studies have found that c-Met plays a critical role in the progression of solid tumors. This study aimed to investigate the expression of c-Met in gastric cancer (GC) and its correlation with preoperative serum tumor markers and prognosis, in order to provide a more theoretical basis for targeting c-Met in the treatment of GC. Methods Ninety-seven patients who underwent curative gastrectomy in our hospital from December 2013 to September 2015 were included in this study. The tissue microarray was constructed by paraffin-embedded tumor tissue of enrolled patients, including 97 GC points and 83 paracancerous points. Then, it was used for c-Met immunohistochemical staining, followed by an immunological H-score. The clinical baseline data and 5-year survival of patients with low and high c-Met expression were compared. Besides, the correlation between the expression of c-Met in tumor tissues and preoperative serum tumor markers was investigated. Finally, multivariate Cox regression analysis was used to explore the survival risk factors of patients. Results c-Met has a high expression rate in GC tissues 64.95% (63/97). The expression of c-Met was significantly different in different clinicopathological stages (p < 0.05); the high expression group also had a higher M stage and clinicopathological stage of GC. The correlation test between the c-Met H-score and CA125 was statistically significant (p = 0.004), indicating a positive correlation. Furthermore, high c-Met expression correlated with poor overall survival (OS) for 5 years (p = 0.005). It was also found that the high expression of c-Met in stage I–II patients was correlative with poor OS for 5 years (p = 0.026), while stage III–IV patients had no statistical significance (p > 0.05). Multivariate Cox regression analysis showed that c-Met might be an independent risk factor for survival 5 years after surgery. Conclusion This study found that the high expression of c-Met in GC tissues was associated with poor 5-year OS in GC patients and was an independent risk factor for 5-year survival after curative gastrectomy. The expression of c-Met in GC tissues was also positively correlated with preoperative serum CA125.
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Affiliation(s)
- Zhengchao Zhang
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730000, China.,Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, 730000, China.,Department of General Surgery, The Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou, 730900, China
| | - Lele Miao
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730000, China.,Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, 730000, China
| | - Song Wang
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730000, China.,Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, 730000, China
| | - Yang Zhao
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730000, China.,Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, 730000, China
| | - Yongqiang Xie
- Department of General Surgery, The Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou, 730900, China
| | - Heng Yun
- Department of General Surgery, The Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou, 730900, China
| | - Zhijian Ren
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730000, China.,Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, 730000, China
| | - Guan Wang
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730000, China.,Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, 730000, China
| | - Muzhou Teng
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730000, China. .,Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, 730000, China.
| | - Yumin Li
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730000, China. .,Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, 730000, China.
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Ertürk SA, Hasbek Z, Özer H. The Relationship Between HER-2 Expression Levels and 18F-FDG PET/CT Parameters in Gastric Cancer. Mol Imaging Radionucl Ther 2021; 30:150-157. [PMID: 34658230 PMCID: PMC8522515 DOI: 10.4274/mirt.galenos.2021.78055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022] Open
Abstract
Objectives: Human epidermal growth factor receptor-2 (HER-2) is a protooncogene encoded by ERBB2 on chromosome 17. 18Fluoridefluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) examination is frequently used to detect distant metastasis in gastric cancer imaging. This study aimed to investigate the relationship between the data obtained in the 18F-FDG PET/CT examination and HER-2 expression status in patients with gastric cancer. Methods: A total of 115 patients diagnosed with gastric cancer between 2016 and 2020, with HER-2 immunohistochemical followed by 18F-FDG PET/CT examination for staging purposes were included. Results: HER-2 immunohistochemical examination revealed 71 patients (61.7%) with negative and 44 (38.3%) with positive results. The median maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) values of patients positive with HER-2 were 9.95, 5, 30.44, and 139.16, respectively, whereas patients negative with HER-2 were 9.3,5.4,36.62, and 190.424, respectively (p>0.05). The median cancer antigen 19-9 (CA 19-9) levels of patients positive with HER-2 was 33.52, whereas 11.79 in those who were negative (p=0.016). The mean age was 69.3±9.35 years in patients with distant metastases, whereas 65.2±10.9 in those without distant metastases (p=0.042). Median SUVmax and SUVmean values in patients with distant metastases were 11.1 and 6.3, respectively, and 8.2 and 4.5 in those without distant metastases (p=0.002 and p=0.001, respectively). The median CA 19-9 and carcinoembryonic antigen (CEA) levels in patients with distant metastases were 31.34 and 9.20, respectively, whereas those without distant metastases were 11.55 and 2.26, respectively (p=0.011 and p=0.001, respectively). Conclusion: In our study, no statistically significant difference was found in terms of HER-2 status, SUVmax, SUVmean, MTV, TLG, distant metastasis, presence of lymph node metastasis, age, gender, tumor diameter, grade, and localization, and CEA levels in patients with gastric cancer. A statistically significant difference was found between HER-2 status and CA 19-9 levels. A statistically significant relationship was found between distant metastases in the 18F-FDG PET/CT examination and SUVmax, SUVmean, age, CEA levels, and histopathologic diagnosis; however, the relationship between distant metastasis in the 18F-FDG PET/CT scan and MTV, TLG, tumor diameter, localization, and grade was not statistically significant.
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Affiliation(s)
- Seyit Ahmet Ertürk
- T.R. Ministry of Health, Tokat State Hospital, Nuclear Medicine Unit, Tokat, Turkey
| | - Zekiye Hasbek
- Sivas Cumhuriyet University Faculty of Medicine, Department of Nuclear Medicine, Sivas, Turkey
| | - Hatice Özer
- Sivas Cumhuriyet University Faculty of Medicine, Department of Pathology, Sivas, Turkey
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Li SQ, Zhang KC, Li JY, Liang WQ, Gao YH, Qiao Z, Xi HQ, Chen L. Establishment and validation of a nomogram to predict the risk of ovarian metastasis in gastric cancer: Based on a large cohort. World J Clin Cases 2020; 8:4331-4341. [PMID: 33083392 PMCID: PMC7559656 DOI: 10.12998/wjcc.v8.i19.4331] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 08/08/2020] [Accepted: 08/26/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Ovarian metastasis is a special type of distant metastasis unique to female patients with gastric cancer. The pathogenesis of ovarian metastasis is incompletely understood, and the treatment options are controversial. Few studies have predicted the risk of ovarian metastasis. It is not clear which type of gastric cancer is more likely to metastasize to the ovary. A prediction model based on risk factors is needed to improve the rate of detection and diagnosis. AIM To analyze risk factors of ovarian metastasis in female patients with gastric cancer and establish a nomogram to predict the probability of occurrence based on different clinicopathological features. METHODS A retrospective cohort of 1696 female patients with gastric cancer between January 2006 and December 2017 were included in a single center, and patients with distant metastasis other than ovary and peritoneum metastasis were excluded. Potential risk factors for ovarian metastasis were analyzed using univariate and multivariable logistic regression. Independent risk factors were chosen to construct a nomogram which received internal validation. RESULTS Ovarian metastasis occurred in 83 of 1696 female patients. Univariate analysis showed that age, Lauren type, whether the primary lesion contained signet-ring cells, vascular tumor emboli, T stage, N stage, the expression of estrogen receptor, the expression of progesterone receptor, serum carbohydrate antigen 125 and the neutrophil-to-lymphocyte ratio were risk factors for ovarian metastasis of gastric cancer (all P < 0.05). Multivariate analysis showed that age ≤ 50 years, Lauren typing of non-intestinal, gastric cancer lesions containing signet-ring cell components, N stage > N2, positive expression of estrogen receptor, serum carbohydrate antigen 125 > 35 U/mL, and a neutrophil-to-lymphocyte ratio > 2.16 were independent risk factors (all P < 0.05). The independent risk factors were constructed into a nomogram model using R language software. The consistency index after continuous correction was 0.840 [95% confidence interval: (0.774-0.906)]. After the internal self-sampling (Bootstrap) test, the calibration curve of the model was obtained with an average absolute error of 0.007. The receiver operating characteristic curve of the obtained model was drawn. The area under the curve was 0.867, the maximal Youden index was 0.613, the corresponding sensitivity was 0.794, and the specificity was 0.819. CONCLUSION The nomogram model performed well in the prediction of ovarian metastasis. Attention should be paid to the possibility of ovarian metastasis in high-risk populations during re-examination, to ensure early detection and treatment.
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Affiliation(s)
- Shao-Qing Li
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
- Institute of General Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Ke-Cheng Zhang
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
- Institute of General Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Ji-Yang Li
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
- Institute of General Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Wen-Quan Liang
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Yun-He Gao
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Zhi Qiao
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Hong-Qing Xi
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Lin Chen
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
- Institute of General Surgery, Chinese PLA General Hospital, Beijing 100853, China
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Complementary Use of Carbohydrate Antigens Lewis a, Lewis b, and Sialyl-Lewis a (CA19.9 Epitope) in Gastrointestinal Cancers: Biological Rationale Towards A Personalized Clinical Application. Cancers (Basel) 2020; 12:cancers12061509. [PMID: 32527016 PMCID: PMC7352550 DOI: 10.3390/cancers12061509] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 06/03/2020] [Accepted: 06/06/2020] [Indexed: 12/14/2022] Open
Abstract
Carbohydrate antigen 19.9 (CA19.9) is used as a tumor marker for clinical and research purposes assuming that it is abundantly produced by gastrointestinal cancer cells due to a cancer-associated aberrant glycosylation favoring its synthesis. Recent data has instead suggested a different picture, where immunodetection on tissue sections matches biochemical and molecular data. In addition to CA19.9, structurally related carbohydrate antigens Lewis a and Lewis b are, in fact, undetectable in colon cancer, due to the down-regulation of a galactosyltransferase necessary for their synthesis. In the pancreas, no differential expression of CA19.9 or cognate glycosyltransferases occurs in cancer. Ductal cells only express such Lewis antigens in a pattern affected by the relative levels of each glycosyltransferase, which are genetically and epigenetically determined. The elevation of circulating antigens seems to depend on the obstruction of neoplastic ducts and loss of polarity occurring in malignant ductal cells. Circulating Lewis a and Lewis b are indeed promising candidates for monitoring pancreatic cancer patients that are negative for CA19.9, but not for improving the low diagnostic performance of such an antigen. Insufficient biological data are available for gastric and bile duct cancer. Studying each patient in a personalized manner determining all Lewis antigens in the surgical specimens and in the blood, together with the status of the tissue-specific glycosylation machinery, promises fruitful advances in translational research and clinical practice.
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