|
1
|
Huang FJ, Fang YY, Wen JY, Li JJ, Lin Q, Su QY, Chen YY, Wang L, Zeng JJ, Chi BT, He RQ, Qin DY, Yang LH, Chen G. From PD-1/PD-L1 to tertiary lymphoid structures: Paving the way for precision immunotherapy in cholangiocarcinoma treatment. Hum Vaccin Immunother 2025; 21:2444697. [PMID: 39757910 DOI: 10.1080/21645515.2024.2444697] [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: 09/17/2024] [Revised: 12/07/2024] [Accepted: 12/16/2024] [Indexed: 01/07/2025] Open
Abstract
Cholangiocarcinoma (CCA) is a highly malignant hepatobiliary tumor characterized by limited treatment options and poor prognosis. The recent rise of immunotherapy has significantly influenced research in this field. This study presents a bibliometric analysis of 416 articles retrieved from the WOSCC, Wan fang Data, CNKI and VIP databases, spanning contributions from 32 countries, 589 institutions and 3,200 authors. The analysis identified "PD-L1," "PD-1" and "pembrolizumab" as central research foci, while "immune checkpoint inhibitors," "tumor immune microenvironment," "tertiary lymphoid structures" and "durvalumab" emerged as key areas of interest. These findings emphasize the pivotal role of immunotherapy in improving survival outcomes for CCA, and they highlight the significance of tertiary lymphoid structures within the tumor microenvironment as a promising target for future research. This study offers a strategic overview of the evolving landscape of CCA immunotherapy, providing valuable insights to guide future scientific endeavors in this domain.
Collapse
Affiliation(s)
- Fang-Ju Huang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Ye-Ying Fang
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Jia-Ying Wen
- Department of Radiotherapy, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Jian-Jun Li
- Department of General Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Qian Lin
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Qin-Yan Su
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Yi-Yang Chen
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Lei Wang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Jian-Jia Zeng
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Bang-Teng Chi
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Rong-Quan He
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Di-Yuan Qin
- Department of Computer Science and Technology, School of Computer and Electronic Information, Guangxi University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Li-Hua Yang
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Gang Chen
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| |
Collapse
|
|
2
|
Peng YT, Pang JS, Lin P, Chen JM, Wen R, Liu CW, Wen ZY, Wu YQ, Peng JB, Zhang L, Yang H, Wen DY, He Y. Preoperative prediction of lymph node metastasis in intrahepatic cholangiocarcinoma: an integrative approach combining ultrasound-based radiomics and inflammation-related markers. BMC Med Imaging 2025; 25:4. [PMID: 39748308 PMCID: PMC11697736 DOI: 10.1186/s12880-024-01542-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Accepted: 12/19/2024] [Indexed: 01/04/2025] Open
Abstract
OBJECTIVES To develop ultrasound-based radiomics models and a clinical model associated with inflammatory markers for predicting intrahepatic cholangiocarcinoma (ICC) lymph node (LN) metastasis. Both are integrated for enhanced preoperative prediction. METHODS This study retrospectively enrolled 156 surgically diagnosed ICC patients. A region of interest (ROI) was manually identified on the ultrasound image of the tumor to extract radiomics features. In the training cohort, we performed a Wilcoxon test to screen for differentially expressed features, and then we used 12 machine learning algorithms to develop 107 models within the cross-validation framework and determine the optimal radiomics model through receiver operating characteristic (ROC) curve analysis. Multivariable logistic regression analysis was used to identify independent risk factors to construct a clinical model. The combined model was established by combining ultrasound-based radiomics and clinical parameters. The Delong test and decision curve analysis (DCA) were used to compare the diagnostic efficacy and clinical utility of different models. RESULTS A total of 1239 radiomics features were extracted from the ROIs of tumors. Among the 107 prediction models, the model (Stepglm + LASSO) utilizing 10 radiomics features ultimately yielded the highest average area under the receiver operating characteristic curve (AUC) of 0.872, with an AUC of 0.916 in the training cohort and 0.827 in the validation cohort. The combined model, which incorporates the optimal radiomics score, clinical N stage, and platelet-to-lymphocyte ratio (PLR), achieved an AUC of 0.882 in the validation cohort, significantly outperforming the clinical model with an AUC of 0.687 (P = 0.009). According to the DCA analysis, the combined model also showed better clinical benefits. CONCLUSIONS The combined model incorporating ultrasound-based radiomics features and the PLR marker offers an effective, noninvasive intelligence-assisted tool for preoperative LN metastasis prediction in ICC patients. CLINICAL TRIAL NUMBER Not applicable.
Collapse
Affiliation(s)
- Yu-Ting Peng
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong, Road, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Jin-Shu Pang
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong, Road, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Peng Lin
- Department of Medical Ultrasound, Fujian Medical University Union Hospital, No.29 Xinquan road, Fuzhou, Fujian Province, China
| | - Jia-Min Chen
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong, Road, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Rong Wen
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong, Road, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Chang-Wen Liu
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong, Road, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Zhi-Yuan Wen
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong, Road, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Yu-Quan Wu
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong, Road, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Jin-Bo Peng
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong, Road, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Lu Zhang
- Department of Medical Pathology, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong, Road, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Hong Yang
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong, Road, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Dong-Yue Wen
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong, Road, Nanning, Guangxi Zhuang Autonomous Region, China.
| | - Yun He
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong, Road, Nanning, Guangxi Zhuang Autonomous Region, China.
| |
Collapse
|
|
3
|
Zhang H, Huang G, Li Q, Wang Y, Yang Z, Chen P, Yuan H, Chen K, Meng B, Yu H. Construction and validation of a novel tumor morphology immune inflammatory nutritional score (TIIN score) for intrahepatic cholangiocarcinoma: a multicenter study. BMC Cancer 2024; 24:630. [PMID: 38783240 PMCID: PMC11112867 DOI: 10.1186/s12885-024-12375-7] [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: 01/02/2024] [Accepted: 05/13/2024] [Indexed: 05/25/2024] Open
Abstract
BACKGROUND Tumor morphology, immune function, inflammatory levels, and nutritional status play critical roles in the progression of intrahepatic cholangiocarcinoma (ICC). This multicenter study aimed to investigate the association between markers related to tumor morphology, immune function, inflammatory levels, and nutritional status with the prognosis of ICC patients. Additionally, a novel tumor morphology immune inflammatory nutritional score (TIIN score), integrating these factors was constructed. METHODS A retrospective analysis was performed on 418 patients who underwent radical surgical resection and had postoperative pathological confirmation of ICC between January 2016 and January 2020 at three medical centers. The cohort was divided into a training set (n = 272) and a validation set (n = 146). The prognostic significance of 16 relevant markers was assessed, and the TIIN score was derived using LASSO regression. Subsequently, the TIIN-nomogram models for OS and RFS were developed based on the TIIN score and the results of multivariate analysis. The predictive performance of the TIIN-nomogram models was evaluated using ROC survival curves, calibration curves, and clinical decision curve analysis (DCA). RESULTS The TIIN score, derived from albumin-to-alkaline phosphatase ratio (AAPR), albumin-globulin ratio (AGR), monocyte-to-lymphocyte ratio (MLR), and tumor burden score (TBS), effectively categorized patients into high-risk and low-risk groups using the optimal cutoff value. Compared to individual metrics, the TIIN score demonstrated superior predictive value for both OS and RFS. Furthermore, the TIIN score exhibited strong associations with clinical indicators including obstructive jaundice, CEA, CA19-9, Child-pugh grade, perineural invasion, and 8th edition AJCC N stage. Univariate and multivariate analysis confirmed the TIIN score as an independent risk factor for postoperative OS and RFS in ICC patients (p < 0.05). Notably, the TIIN-nomogram models for OS and RFS, constructed based on the multivariate analysis and incorporating the TIIN score, demonstrated excellent predictive ability for postoperative survival in ICC patients. CONCLUSION The development and validation of the TIIN score, a comprehensive composite index incorporating tumor morphology, immune function, inflammatory level, and nutritional status, significantly contribute to the prognostic assessment of ICC patients. Furthermore, the successful application of the TIIN-nomogram prediction model underscores its potential as a valuable tool in guiding individualized treatment strategies for ICC patients. These findings emphasize the importance of personalized approaches in improving the clinical management and outcomes of ICC.
Collapse
Affiliation(s)
- Haofeng Zhang
- Department of Hepatobiliary and Pancreatic Surgery, People's Hospital of Zhengzhou University, Zhengzhou, 450000, China
- Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou, 450000, China
| | - Guan Huang
- Department of Hepatobiliary and Pancreatic Surgery, People's Hospital of Zhengzhou University, Zhengzhou, 450000, China
- Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou, 450000, China
| | - Qingshan Li
- Department of Hepatobiliary and Pancreatic Surgery, People's Hospital of Zhengzhou University, Zhengzhou, 450000, China
- Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou, 450000, China
| | - Yanbo Wang
- Department of Hepatobiliary and Pancreatic Surgery, People's Hospital of Zhengzhou University, Zhengzhou, 450000, China
- Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou, 450000, China
| | - Zhenwei Yang
- Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou, 450000, China
| | - Pengyu Chen
- Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou, 450000, China
| | - Hao Yuan
- Department of Hepatobiliary and Pancreatic Surgery, People's Hospital of Zhengzhou University, Zhengzhou, 450000, China
- Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou, 450000, China
| | - Kunlun Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China
| | - Bo Meng
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Hospital of Zhengzhou University, Zhengzhou, 450000, China
| | - Haibo Yu
- Department of Hepatobiliary and Pancreatic Surgery, People's Hospital of Zhengzhou University, Zhengzhou, 450000, China.
- Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou, 450000, China.
| |
Collapse
|
|
4
|
Huang G, Zhang H, Yang Z, Li Q, Yuan H, Chen P, Xie C, Meng B, Zhang X, Chen K, Yu H. Predictive value of HTS grade in patients with intrahepatic cholangiocarcinoma undergoing radical resection: a multicenter study from China. World J Surg Oncol 2024; 22:17. [PMID: 38200585 PMCID: PMC10782600 DOI: 10.1186/s12957-023-03281-6] [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: 09/11/2023] [Accepted: 12/09/2023] [Indexed: 01/12/2024] Open
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (ICC) is a highly malignant tumor with a poor prognosis. This study aimed to investigate whether Hemoglobin, Albumin, Lymphocytes, and Platelets (HALP) score and Tumor Burden Score (TBS) serves as independent influencing factors following radical resection in patients with ICC. Furthermore, we sought to evaluate the predictive capacity of the combined HALP and TBS grade, referred to as HTS grade, and to develop a prognostic prediction model. METHODS Clinical data for ICC patients who underwent radical resection were retrospectively analyzed. Univariate and multivariate Cox regression analyses were first used to find influencing factors of prognosis for ICC. Receiver operating characteristic (ROC) curves were then used to find the optimal cut-off values for HALP score and TBS and to compare the predictive ability of HALP, TBS, and HTS grade using the area under these curves (AUC). Nomogram prediction models were constructed and validated based on the results of the multivariate analysis. RESULTS Among 423 patients, 234 (55.3%) were male and 202 (47.8) were aged ≥ 60 years. The cut-off value of HALP was found to be 37.1 and for TBS to be 6.3. Our univariate results showed that HALP, TBS, and HTS grade were prognostic factors of ICC patients (all P < 0.05), and ROC results showed that HTS had the best predictive value. The Kaplan-Meier curve showed that the prognosis of ICC patients was worse with increasing HTS grade. Additionally, multivariate regression analysis showed that HTS grade, carbohydrate antigen 19-9 (CA19-9), tumor differentiation, and vascular invasion were independent influencing factors for Overall survival (OS) and that HTS grade, CA19-9, CEA, vascular invasion and lymph node invasion were independent influencing factors for recurrence-free survival (RFS) (all P < 0.05). In the first, second, and third years of the training group, the AUCs for OS were 0.867, 0.902, and 0.881, and the AUCs for RFS were 0.849, 0.841, and 0.899, respectively. In the first, second, and third years of the validation group, the AUCs for OS were 0.727, 0.771, and 0.763, and the AUCs for RFS were 0.733, 0.746, and 0.801, respectively. Through the examination of calibration curves and using decision curve analysis (DCA), nomograms based on HTS grade showed excellent predictive performance. CONCLUSIONS Our nomograms based on HTS grade had excellent predictive effects and may thus be able to help clinicians provide individualized clinical decision for ICC patients.
Collapse
Affiliation(s)
- Guan Huang
- Department of Hepatobiliary Surgery, People's Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Haofeng Zhang
- Department of Hepatobiliary Surgery, People's Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Zhenwei Yang
- Department of Hepatobiliary Surgery, People's Hospital of Henan University, Zhengzhou, Henan Province, China
| | - Qingshan Li
- Department of Hepatobiliary Surgery, Henan Province People's Hospital, Zhengzhou, Henan Province, China
| | - Hao Yuan
- Department of Hepatobiliary Surgery, People's Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Pengyu Chen
- Department of Hepatobiliary Surgery, People's Hospital of Henan University, Zhengzhou, Henan Province, China
| | - Chenxi Xie
- Department of Hepatobiliary Surgery, People's Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Bo Meng
- Department of Hepatobiliary Surgery, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Xianzhou Zhang
- Department of Hepatobiliary Surgery, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Kunlun Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Haibo Yu
- Department of Hepatobiliary Surgery, People's Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
| |
Collapse
|
|
5
|
Lv Y, Liu H, He P, Xie S, Yin X, Cai Y, Wu H. A novel model for predicting the prognosis of postoperative intrahepatic cholangiocarcinoma patients. Sci Rep 2023; 13:19267. [PMID: 37935735 PMCID: PMC10630332 DOI: 10.1038/s41598-023-45056-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 10/15/2023] [Indexed: 11/09/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) accounts for 20% of liver malignancies with a 5-year survival rate of 35% at best with limited prognostic predictors. Lung Immune Prognostic Index (LIPI) is a novel prognostic factor in pulmonary cancers. In this study, we developed a modified prognostic model from LIPI called intrahepatic immune prognostic index (IIPI) for ICC. A retrospectively study was conducted at Liver Transplant Center of West China Hospital between January 2015 and January 2023. Hematological factors and clinical features of ICC patients were collected and analyzed. The area under curve (AUC) and optimal cuff-off of each single hematological factor was calculated. In this study, derived neurtrophil to lymphocyte ratio (dNLR), arbohydrate antigen199 (CA199) and carcinoembryonic antigen (CEA) have higher AUC values. LIPI was composed of dNLR and was further modified by combing CA199 and CEA, forming the IIPI. The IIPI consists of four grades which are None, Light, Moderate and Severe. Compared to other prognostic factors, IIPI exhibited better ability to predict overall survival. The multivariate analysis indicated that cirrhosis, differentiation, hilar invasion and IIPI were independent prognostic factors for ICC patients. An IIPI-based nomogram was also established and could predict the overall survival. In addition, the subgroup analyses based on clinical prognostic factors showed that the IIPI exhibited excellent prognostic influence. IIPI model is suitable for predicting the prognosis of postoperative ICC patients. Further research is needed to explore the relationship between postoperative recurrence and metastasis of ICC patients and IIPI.
Collapse
Affiliation(s)
- Yinghao Lv
- Liver Transplant Center, Transplant Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, 610041, Sichuan Province, China
| | - Hu Liu
- Liver Transplant Center, Transplant Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, 610041, Sichuan Province, China
| | - Penghui He
- Liver Transplant Center, Transplant Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, 610041, Sichuan Province, China
| | - Sinan Xie
- Liver Transplant Center, Transplant Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, 610041, Sichuan Province, China
| | - Xiuchun Yin
- Ward of Liver Transplant Centre and Vascular Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yunshi Cai
- Liver Transplant Center, Transplant Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, 610041, Sichuan Province, China.
| | - Hong Wu
- Liver Transplant Center, Transplant Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, 610041, Sichuan Province, China.
| |
Collapse
|
|
6
|
Zhang H, Li Q, Huang G, Yang Z, Chen K, Meng B, Yu H. Construction and validation of a novel prognostic model for intrahepatic cholangiocarcinoma based on a combined scoring system of systemic immune-inflammation index and albumin-bilirubin: a multicenter study. Front Oncol 2023; 13:1239375. [PMID: 37841429 PMCID: PMC10569214 DOI: 10.3389/fonc.2023.1239375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 09/11/2023] [Indexed: 10/17/2023] Open
Abstract
Background The degree of inflammation and immune status is widely recognized to be associated with intrahepatic cholangiocarcinoma (ICC) and is closely linked to poor postoperative survival. The purpose of this study was to evaluate whether the systemic immune-inflammatory index (SII) and the albumin bilirubin (ALBI) grade together exhibit better predictive strength compared to SII and ALBI separately in patients with ICC undergoing curative surgical resection. Methods A retrospective analysis was performed on a cohort of 374 patients with histologically confirmed ICC who underwent curative surgical resection from January 2016 to January 2020 at three medical centers. The cohort was divided into a training set comprising 258 patients and a validation set consisting of 116 patients. Subsequently, the prognostic predictive abilities of three indicators, namely SII, ALBI, and SII+ALBI grade, were evaluated. Independent risk factors were identified through univariate and multivariate analyses. The identified independent risk factors were then utilized to construct a nomogram prediction model, and the predictive strength of the nomogram prediction model was assessed through Receiver Operating Characteristic (ROC) survival curves and calibration curves. Results Univariate analysis of the training set, consisting of 258 eligible patients with ICC, revealed that SII, ALBI, and SII+ALBI grade were significant prognostic factors for overall survival (OS) and recurrence-free survival (RFS) (p < 0.05). Multivariate analysis revealed the independent significance of SII+ALBI grade as a risk factor for postoperative OS and RFS (p < 0.05). Furthermore, we conducted an analysis of the correlation between SII, ALBI, SII+ALBI grade, and clinical features, indicating that SII+ALBI grade exhibited stronger associations with clinical and pathological characteristics compared to SII and ALBI. We constructed a predictive model for postoperative survival in ICC based on SII+ALBI grade, as determined by the results of multivariate analysis. Evaluation of the model's predictive strength was performed through ROC survival curves and calibration curves in the training set and validation set, revealing favorable predictive performance. Conclusion The SII+ALBI grade, a novel classification based on inflammatory and immune status, serves as a reliable prognostic indicator for postoperative OS and RFS in patients with ICC.
Collapse
Affiliation(s)
- Haofeng Zhang
- Department of Hepatobiliary and Pancreatic Surgery, People’s Hospital of Zhengzhou University, Zhengzhou, China
- Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Qingshan Li
- Department of Hepatobiliary and Pancreatic Surgery, People’s Hospital of Zhengzhou University, Zhengzhou, China
- Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Guan Huang
- Department of Hepatobiliary and Pancreatic Surgery, People’s Hospital of Zhengzhou University, Zhengzhou, China
- Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Zhenwei Yang
- Department of Hepatobiliary and Pancreatic Surgery, People’s Hospital of Henan University, Zhengzhou, China
| | - Kunlun Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Bo Meng
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Haibo Yu
- Department of Hepatobiliary and Pancreatic Surgery, People’s Hospital of Zhengzhou University, Zhengzhou, China
- Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People’s Hospital, Zhengzhou, China
| |
Collapse
|
|
7
|
Li J, Gao L, Liu T, Feng D. Association of systemic inflammation index with survival in patients with advanced perihilar cholangiocarcinoma treated with interventional therapy. Front Oncol 2022; 12:1038759. [PMID: 36620590 PMCID: PMC9815453 DOI: 10.3389/fonc.2022.1038759] [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: 09/07/2022] [Accepted: 12/07/2022] [Indexed: 12/24/2022] Open
Abstract
Objective Immunity and inflammation are key mediators of carcinoma development, invasion and metastasis. However, it remains unknown whether the systemic immune-inflammation index (SII) can be used as a prognostic indicator for cholangiocarcinoma. In this study, we investigated the association and predictive value of the SII with the prognosis of advanced perihilar cholangiocarcinoma (pCCA) after interventional therapy. Methods A retrospective cohort of patients with advanced pCCA treated with interventional therapy at the First Hospital of Shanxi Medical University enrolled in this study from January 2019 through January 2021 was examined. Cox regression models were used to analyze the relationship between the SII and overall survival (OS) of patients with advanced pCCA. Receiver operating characteristic (ROC) analysis was used to evaluate the predictive power of SII. Results Preoperative SII was positively associated with poor OS of pCCA after interventional therapy, with corresponding hazard ratios (HR) of 1.57 (95% CI: 1.17 - 2.10) for an inter-quartile range increase. The predictive power of SII was higher than that of other inflammation indexes based on ROC analysis (AUC = 0.835 [95% CI (0.731 - 0.940)]). The optimal cut-off values, sensitivity, and specificity with SII were 700, 0.774 and 0.846, respectively. An SII ≥ 700 was significantly associated with lymph node metastasis and high carbohydrate antigen199 (CA199) level. In multivariate analyses, total bilirubin, carbohydrate antigen 199, vascular invasion, and SII independently predicted overall survival (P < 0.05). Conclusion This is the first study demonstrating that an increase in the SII is associated with poor advanced pCCA prognosis, and could serve as a reliable prognostic indicator of pCCA after interventional therapy.
Collapse
Affiliation(s)
- Jinyu Li
- Department of Oncological and Vascular Intervention, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Long Gao
- Department of Oncological and Vascular Intervention, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Tianci Liu
- College of Medical Imaging, Shanxi Medical University, Taiyuan, China
| | - Duiping Feng
- Department of Oncological and Vascular Intervention, First Hospital of Shanxi Medical University, Taiyuan, China,*Correspondence: Duiping Feng,
| |
Collapse
|
|
8
|
Peng X, Wang X, Hua L, Yang R. Prognostic and Clinical Value of the Systemic Immune-Inflammation Index in Biliary Tract Cancer: A Meta-Analysis. J Immunol Res 2022; 2022:6988489. [PMID: 36438200 PMCID: PMC9691295 DOI: 10.1155/2022/6988489] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 09/26/2022] [Accepted: 10/18/2022] [Indexed: 08/10/2023] Open
Abstract
Previous studies that explored the prognostic and clinical value of the systemic immune-inflammation index (SII) in biliary tract cancer (BTC) had inconsistent results. We conducted this meta-analysis to evaluate the prognostic and clinicopathological role of the SII in biliary tract cancer. Combined analysis demonstrated that high SII levels had worse overall survival (HR = 1.92, 95% CI: 1.66-2.21, p < 0.001) than those with low SII levels. And an elevated SII was associated with lymph node metastasis (OR = 1.44, 95% CI = 1.18-1.76; p < 0.001), TNM stage (OR = 1.49, 95% CI = 1.05-2.13; p = 0.028), and vascular invasion (OR = 1.49, 95% CI = 1.05-2.13; p = 0.028). Conversely, no significant association between a high SII and sex or tumor differentiation was found. Our findings demonstrate that high SII levels were correlated with unfavorable survival outcomes among patients with BTC and that they were also correlated with some higher malignancy features of BTC.
Collapse
Affiliation(s)
- Xiulan Peng
- Department of Oncology, The Second Affiliated Hospital of Jianghan University, the Fifth Hospital of Wuhan, Wuhan, Hubei 430000, China
| | - Xia Wang
- Department of Pharmacy, The Second Affiliated Hospital of Jianghan University, the Fifth Hospital of Wuhan, Wuhan, Hubei 430000, China
| | - Li Hua
- Department of General Medicine, The Second Affiliated Hospital of Jianghan University, the Fifth Hospital of Wuhan, Wuhan, Hubei province, 430050, China
| | - Rui Yang
- Department of Vascular Surgery, The Second Affiliated Hospital of Jianghan University, the Fifth Hospital of Wuhan, Wuhan, Hubei 430000, China
| |
Collapse
|
|
9
|
Zhang B, Yao W. Prognostic role of the systemic immune-inflammation index in biliary tract cancers: a meta-analysis of 3,515 patients. World J Surg Oncol 2022; 20:320. [PMID: 36171621 PMCID: PMC9519406 DOI: 10.1186/s12957-022-02783-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 09/12/2022] [Indexed: 11/10/2022] Open
Abstract
Background The systemic immune-inflammation index (SII) is an inflammatory parameter calculated as platelet count × neutrophil count/lymphocyte count in the peripheral blood. In recent years, the prognostic role of the SII in patients with biliary tract cancer (BTC) has been gradually investigated. However, the results were controversial. This meta-analysis aimed to illustrate the prognostic value of the SII in BTC. Methods The electronic databases of PubMed, the Web of Science, Embase, and the Cochrane Library were thoroughly retrieved up to April 15, 2022. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to evaluate the prognostic value of the SII for clinical outcomes. The association between the SII and overall survival (OS) and recurrence-free survival (RFS)/progression-free survival (PFS) was evaluated. Results Thirteen studies involving 3515 patients were included in this meta-analysis. The pooled results indicated that an elevated SII was significantly associated with poor OS (HR, 1.77; 95% CI, 1.47–2.14; p<0.001) and RFS/PFS (HR, 1.66; 95% CI, 1.38–1.99; p<0.001) in patients with BTC. Subgroup analysis stratified by country, sample size, and cutoff value showed similar results. The sensitivity analysis and publication bias test confirmed the reliability of our results. Conclusions An elevated pretreatment SII was significantly associated with worse OS and RFS/PFS in patients with BTC. Our results suggest that the SII is a valuable and cost-effective prognostic parameter for the treatment of patients with BTC. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-022-02783-z.
Collapse
Affiliation(s)
- Buwen Zhang
- Department of Oncology, Changxing People's Hospital, Huzhou, 313100, Zhejiang, China
| | - Weiyun Yao
- Department of Hepatobiliary Surgery, Changxing People's Hospital, Huzhou, 313100, Zhejiang, China.
| |
Collapse
|
|
10
|
Chen L, Chen L, Wang YY, Zhang LX, Xia XG. A predictive model of bowel resection for incarcerated inguinal hernia based on the systemic immune-inflammation index. Front Surg 2022; 9:990481. [PMID: 36211270 PMCID: PMC9537729 DOI: 10.3389/fsurg.2022.990481] [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: 07/10/2022] [Accepted: 09/06/2022] [Indexed: 11/26/2022] Open
Abstract
Background and Purpose An inguinal hernia is a common surgical disease. Once incarcerated or strangulated, it may endanger the life of the patient. Therefore, it is essential to study the risk factors of incarcerated inguinal hernia (IIH) and strangulated inguinal hernia (SIH). One of the serious complications of IIH and SIH is intestinal necrosis, which occurs owing to blood supply disorder. The study explores the risk factors of intestinal resection and establishes a simple model to assess the incidence of intestinal resection to provide significant assistance and limited guidance for clinical work. Patients and Methods Our research team collected and retrospectively analysed the clinical data of 338 patients with IIH who were hospitalized in the First Affiliated Hospital of Wenzhou Medical University between September 2008 and December 2016. According to the surgical plan, we divided the included cases into two groups, non-intestinal and intestinal resection groups, and the clinical case characteristics of these groups were statistically analysed. Results Based on multivariable logistic regression analysis, we found that increased risk of bowel resection was highly correlated among the elderly (≥70 years), and for people with high temperature (≥37.3°C), high systemic immune-inflammation index(SII) values (≥1230.13), presence of bowel obstruction, and signs of peritonitis. Further, we processed the five independent risk factors using special software to obtain a simple model called a nomogram. To verify the nomogram’s accuracy and predictive ability, we calculate the C-index: 0.806 and use the calibration curve to evaluate its stability and predictive performance. We constructed the ROC curve nomogram and other sub-variables, and calculated the area under the curve (AUC) corresponding to the nomogram (AUC = 0.808, 95% CI = 0.762 to 0.848), SII (AUC = 0.752, 95% CI = 0.703 to 0.797), age (AUC = 0.641, 95% CI = 0.587 to 0.692), temperature (AUC = 0.579, 95% CI = 0.524 to 0.632), bowel obstruction (AUC = 0.685, 95% CI = 0.633 to 0.734), and signs of peritonitis (AUC = 0.580, 95% CI = 0.525 to 0.633). Conclusion It can be said that we found for the first time that clinical variables such as SII are independent risk factors for enterectomy for IIH. The nomogram based on SII and other variables can accurately and easily predict the probability of IIH requiring bowel resection.
Collapse
Affiliation(s)
- Lei Chen
- Department of General Surgery, Xiang’an Hospital of Xiamen University, Xiamen, China
- Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Lei Chen
- Department of Emergency, Xiang’an Hospital of Xiamen University, Xiamen, China
| | - Ying-ying Wang
- Department of Neurology, Xiang’an Hospital of Xiamen University, Xiamen, China
| | - Li-xiang Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Correspondence: Lixiang Zhang Xiao-Gang Xia
| | - Xiao-gang Xia
- Department of General Surgery, Xiang’an Hospital of Xiamen University, Xiamen, China
- Correspondence: Lixiang Zhang Xiao-Gang Xia
| |
Collapse
|
|
11
|
Liu XC, Jiang YP, Sun XG, Zhao JJ, Zhang LY, Jing X. Prognostic Significance of the Systemic Immune-Inflammation Index in Patients With Cholangiocarcinoma: A Meta-Analysis. Front Oncol 2022; 12:938549. [PMID: 35875153 PMCID: PMC9300870 DOI: 10.3389/fonc.2022.938549] [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: 05/07/2022] [Accepted: 06/13/2022] [Indexed: 11/30/2022] Open
Abstract
Background The systemic immune-inflammation index (SII) is a significant prognostic factor for neoplastic diseases. However, the prognostic value of SII in patients with cholangiocarcinoma (CCA) remains unclear. This meta-analysis aimed to investigate the prognostic value of preoperative SII in patients with CCA. Method We systematically searched for relevant studies in PubMed, Scopus, EMBASE, Web of Science, PROSPERO, and Cochrane Library databases up to March 22, 2022. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the association between SII and survival outcomes, including overall survival (OS) and recurrence-free survival. Results Five studies with 1402 patients were included in this meta-analysis to determine the prognostic value of preoperative SII. The results showed that a higher SII was associated with poor OS in patients with CCA who underwent invasive surgery (HR=1.916; 95% CI, 1.566–2.343; Z=6.329; P<0.001). The results were reliable in the subgroup analysis according to country, age, sample size, SII cutoff values, and treatment methods. Conclusions A high preoperative SII appears to be an effective and practical method for monitoring survival in patients with CCA. Systematic Review Registration International Platform of Registered Systematic. Review and Meta-Analysis Protocols (INPLASY), identifier INPLASY202240015.
Collapse
|
|
12
|
Toyoda J, Sahara K, Maithel SK, Abbott DE, Poultsides GA, Wolfgang C, Fields RC, He J, Scoggins C, Idrees K, Shen P, Endo I, Pawlik TM. Prognostic Utility of Systemic Immune-Inflammation Index After Resection of Extrahepatic Cholangiocarcinoma: Results from the U.S. Extrahepatic Biliary Malignancy Consortium. Ann Surg Oncol 2022; 29:7605-7614. [PMID: 35768667 DOI: 10.1245/s10434-022-12058-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 06/05/2022] [Indexed: 12/18/2022]
Abstract
BACKGROUND We sought to define the association of the systemic immune inflammation index (SII) with prognosis and adjuvant therapy benefit among patients undergoing resection of extrahepatic cholangiocarcinoma (eCCA). METHODS The impact of SII on overall (OS) and recurrence-free survival (RFS) following resection of eCCA was assessed and compared with other inflammatory markers and traditional prognostic factors. Propensity score matching (PSM) was used to determine the impact of adjuvant therapy (AT) on OS and RFS relative to low versus high SII. RESULTS Patients with high versus low SII had worse 5-year OS (15.9% vs. 27.9%) and RFS (12.4% vs. 20.9%) (both p < 0.01). On multivariate analysis, high SII remained associated with worse OS (HR = 1.50, 95% CI 1.20-1.87) and RFS (HR = 1.46, 95% CI 1.18-1.81). Patients with T1/2 disease and a high-SII had worse 5-year OS versus individuals with T3/4 disease and low-SII (5-year OS: T1/2 & low-SII 35.6%, T1/2 & high-SII 16.4%, T3/4 & low-SII 22.1%, T3/4 & high-SII 15.6%, p < 0.01). Similarly, 5-year OS was comparable among individuals with N0 and high-SII versus N1 and low-SII (5-year OS: N0 & high-SII 23.2%, N1 and low-SII 19.8%, p = 0.95). On PSM, AT improved OS and RFS among patients with high SII (5-year OS: 22.5% vs. 12.3%, p < 0.01, 5-year RFS: 19.0% vs. 12.5%; p = 0.01) but not individuals with low SII (5-year OS: 22.9% vs. 26.9%; p = 0.98, 5-year RFS: 18.5% vs. 19.9%; p = 0.94). CONCLUSIONS SII was independently associated with postoperative OS and RFS following curative-intent resection of eCCA. High SII up-staged patients relative T- and N-categories and identified patients with high SII as the most likely to benefit from AT.
Collapse
Affiliation(s)
- Junya Toyoda
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Kota Sahara
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan.,Department of Surgery, The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Daniel E Abbott
- Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
| | - George A Poultsides
- Department of Surgery, Stanford University Medical Center, Stanford, CA, USA
| | | | - Ryan C Fields
- Department of Surgery, Washington University School of Medicine, St Louis, MO, USA
| | - Jin He
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Charles Scoggins
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Kamran Idrees
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Perry Shen
- Department of Surgery, Wake Forest University, Winston-Salem, NC, USA
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH, USA.
| |
Collapse
|
|
13
|
Li H, Liu R, Li J, Li J, Wu H, Wang G, Li Z, Li D. Prognostic significance of gamma-glutamyl transpeptidase to albumin ratio in patients with intrahepatic cholangiocarcinoma after hepatectomy. J Cell Mol Med 2022; 26:3196-3202. [PMID: 35481993 PMCID: PMC9170822 DOI: 10.1111/jcmm.17321] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 03/13/2022] [Accepted: 03/30/2022] [Indexed: 02/05/2023] Open
Abstract
Inflammation has been reported to play an important role in tumour progression and prognosis. In this study, we evaluated the prognostic significance of γ-glutamyl transpeptidase (GGT) to albumin ratio (GAR) in patients with intrahepatic cholangiocarcinoma (ICC) after hepatectomy. We retrospectively analysed 650 ICC patients underwent hepatectomy at three Chinese medical centres between January 2009 and September 2017. Patients were classified into derivation cohort (n = 509) and validation cohort (n = 141). Receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value for GAR. Survival curve and cox regression analysis were applied to assess the prognostic power of GAR. The prognostic accuracy of GAR was compared with other variables by ROC curve. The optimal cut-off value for GAR was 1.3655. Preoperative high GAR was closely related to tumour number, lymph node invasion and GGT. The survival curve of derivation and validation cohorts showed that patients in the high GAR group had significantly shorter overall survival (OS) and disease-free survival (DFS) than patients in the low GAR group. Multivariate analysis in the derivation cohort confirmed that GAR was an independent prognostic factor for survival outcomes. Moreover, the ROC curve revealed that GAR had better predictive accuracy than other variables. High GAR predicted poor OS and DFS in ICC patients after hepatectomy. GAR may be a novel, simple and effective prognostic marker for ICC patients.
Collapse
Affiliation(s)
- Hui Li
- Department of Hepatobiliary Pancreatic Tumor CenterChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized TreatmentChongqing University Cancer HospitalChongqingChina
| | - Rongqiang Liu
- Department of Hepatobiliary Pancreatic Tumor CenterChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized TreatmentChongqing University Cancer HospitalChongqingChina
| | - Jiawang Li
- Department of Hepatobiliary Pancreatic Tumor CenterChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized TreatmentChongqing University Cancer HospitalChongqingChina
| | - Jiaxin Li
- Department of Liver Surgery & Liver TransplantationWest China HospitalSichuan UniversityChengduChina
| | - Hong Wu
- Department of Liver Surgery & Liver TransplantationWest China HospitalSichuan UniversityChengduChina
| | - Genshu Wang
- Department of Hepatic Surgery and Liver Transplantation CenterThe Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Zhenhua Li
- Department of Head and Neck SurgeryChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized TreatmentChongqing University Cancer HospitalChongqingChina
| | - Dewei Li
- Department of Hepatobiliary Pancreatic Tumor CenterChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized TreatmentChongqing University Cancer HospitalChongqingChina
| |
Collapse
|
|
14
|
Li W, Ma G, Deng Y, Chen W, Liu Z, Chen F, Wu Q. Systemic Immune-Inflammation Index Is a Prognostic Factor for Breast Cancer Patients After Curative Resection. Front Oncol 2021; 11:570208. [PMID: 34926234 PMCID: PMC8671143 DOI: 10.3389/fonc.2021.570208] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Accepted: 10/12/2021] [Indexed: 02/05/2023] Open
Abstract
Background The preoperative systemic immune-inflammation index (SII) is correlated with prognosis in several malignancies. The aim of this study was to investigate the prognosis value of SII in patients with resected breast cancer. Materials and Methods A total of 784 breast cancer patients who underwent surgical resection were consecutively investigated. The optimal cutoff value of SII was evaluated using the receiver operating characteristic (ROC) curve. The collection of SII with clinicopathological characteristic and prognosis was further evaluated. Results The optimal cutoff value for SII in the prediction of survival was 514 according to ROC curve analysis. A high SII was significantly correlated with younger age (P = 0.037), PR status (P < 0.001), and HER2 status (P = 0.035). Univariate analysis revealed that SII (P < 0.001), T-stage (P < 0.001), lymph node involvement post-surgery (P = 0.024), and histological grade (P < 0.001) were significantly related to DFS, and SII (P < 0.001), T-stage (P = 0.003), lymph node involvement post-surgery (P = 0.006), and histological grade (P < 0.001) were significantly associated with OS. In multivariate analysis, a high SII was an independent worse prognostic factor for DFS (HR, 4.530; 95% CI, 3.279-6.258; P < 0.001) and OS (HR, 3.825; 95% CI, 2.594-5.640; P < 0.001) in all the enrolled patients. Furthermore, subgroup analysis of molecular subtype revealed that SII was significantly associated with prognosis in all subtypes. Conclusion Preoperative SII is a simple and useful prognostic factor for predicting long-term outcomes for breast cancer patients undergoing surgery.
Collapse
Affiliation(s)
- Wen Li
- Lung Cancer Center & Institute, West China Hospital, Sichuan University, Chengdu, China
| | - Guangzhi Ma
- Lung Cancer Center & Institute, West China Hospital, Sichuan University, Chengdu, China
| | - Yunfu Deng
- Lung Cancer Center & Institute, West China Hospital, Sichuan University, Chengdu, China.,Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Wenjie Chen
- Lung Cancer Center & Institute, West China Hospital, Sichuan University, Chengdu, China.,Department of Thoracic Surgery, The Third Affifiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming, China
| | - Zhenkun Liu
- Lung Cancer Center & Institute, West China Hospital, Sichuan University, Chengdu, China
| | - Fang Chen
- Breast Center, West China Hospital, Sichuan University, Chengdu, China
| | - Qiang Wu
- Lung Cancer Center & Institute, West China Hospital, Sichuan University, Chengdu, China
| |
Collapse
|
|
15
|
Xu YP, Dong ZN, Wang SW, Zheng YM, Zhang C, Zhou YQ, Zhao YJ, Zhao Y, Wang F, Peng R, Tang MC, Bai DS, Huang XY, Guo CY. circHMGCS1-016 reshapes immune environment by sponging miR-1236-3p to regulate CD73 and GAL-8 expression in intrahepatic cholangiocarcinoma. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2021; 40:290. [PMID: 34526098 PMCID: PMC8442376 DOI: 10.1186/s13046-021-02095-2] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 09/06/2021] [Indexed: 12/30/2022]
Abstract
Background Accumulating evidence indicates that circRNAs may serve as essential regulators in the progression of several human cancers, but the function and mechanism of circRNAs in intrahepatic cholangiocarcinoma (ICC) are largely unknown. Methods RNA-seq was used to assess differentially expressed circRNAs between 4 ICC and peritumor tissues. Quantitative RT-PCR and in situ hybridization were used to determine the circHMGCS1–016 expression in ICC tissues. The function and mechanism of circHMGCS1–016 were further identified via in vivo experiments. The clinical characteristics and prognostic significance of circHMGCS1–016 were analyzed by a retrospective study. The functions of circHMGCS1–016 were assessed via modifying circRNA expression in ICC cells. Moreover, the molecular mechanisms of circHMGCS1–016 in ICC cells were explored by circRNA precipitation, miRNA immunoprecipitation, SILAC and luciferase reporter assays. Results We identified that compared with peritumor tissues, ICC tissues expressed hsa_circ_0008621 (circHMGCS1–016) high by RNA-seq, which was further identified by qRT-PCR and in situ hybridization. Moreover, the expression of circHMGCS1–016 was revealed to be associated with survival and recurrence of ICC patients. By regulating circHMGCS1–016 expression, we found that elevated circHMGCS1–016 promoted ICC development both in vitro and in vivo. By SILAC and circRNA-pull down, we demonstrated that circHMGCS1–016 induced ICC cell invasion and reshaped the tumor immune microenvironment via the miR-1236-3p/CD73 and GAL-8 axis. In ICC tissues, we uncovered that a high level of circHMGCS1–016 was positively associated with CD73 and GAL-8 expression and negatively related to the CD8+ T cells infiltration, which was further validated by establishing a humanized mouse tumor model. Importantly, we displayed that ICC patients with high levels of circHMGCS1–016 in tumor tissues benefited less from anti-PD1 treatment compared to those with low levels of circHMGCS1–016. Conclusions CircHMGCS1–016 is a forceful contributor in ICC development and immune tolerance via miR-1236-3p/CD73 and GAL-8 axis. CircHMGCS1–016 can be explored as a new potential biomarker and therapeutic target for PD1-resistant ICC. Supplementary Information The online version contains supplementary material available at 10.1186/s13046-021-02095-2.
Collapse
Affiliation(s)
- Ya-Ping Xu
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Ze-Ning Dong
- Xiangya Medical College, Central South University, Changsha, Hunan, 410008, P. R. China.,Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Shanghai, 200032, P. R. China
| | - Si-Wei Wang
- Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Shanghai, 200032, P. R. China
| | - Yi-Min Zheng
- Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Shanghai, 200032, P. R. China
| | - Chi Zhang
- Department of Hepatobiliary and Pancreatic Surgery, Subei People's Hospital, Clinical Medical School, Yangzhou University Affiliated Hospital, Yangzhou, China
| | - Ying-Qun Zhou
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Yu-Jie Zhao
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Yan Zhao
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Feng Wang
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Rui Peng
- Department of Hepatobiliary and Pancreatic Surgery, Subei People's Hospital, Clinical Medical School, Yangzhou University Affiliated Hospital, Yangzhou, China
| | - Mao-Chun Tang
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Dou-Sheng Bai
- Department of Hepatobiliary and Pancreatic Surgery, Subei People's Hospital, Clinical Medical School, Yangzhou University Affiliated Hospital, Yangzhou, China.
| | - Xiao-Yong Huang
- Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Shanghai, 200032, P. R. China.
| | - Chuan-Yong Guo
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
| |
Collapse
|
|
16
|
Deng LM, Wang Y, Yang JH, Li JL, Chen ZY, Bao WM, Chen KY, Yao XF, Zheng CM, Zheng JY, Yu ZP, Jin B, Chen G. Diffuse reduction of spleen density is a novel prognostic marker for intrahepatic cholangiocarcinoma after curative resection. World J Gastrointest Oncol 2021; 13:929-942. [PMID: 34457196 PMCID: PMC8371520 DOI: 10.4251/wjgo.v13.i8.929] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 05/14/2021] [Accepted: 07/09/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Diffuse reduction of spleen density (DROSD) is related to cancer prognosis; however, its role in intrahepatic cholangiocarcinoma (ICC) remains unclear.
AIM To assess the predictive value of DROSD in the prognosis of ICC after curative resection.
METHODS In this multicenter retrospective cohort study, we enrolled patients with ICC who underwent curative hepatectomy between 2012 and 2019. Preoperative spleen density was measured using computed tomography. Overall survival (OS) and recurrence-free survival (RFS) rates were calculated and compared utilizing the Kaplan–Meier method. Univariable and multivariable Cox regression analyses were applied to identify independent factors for OS and RFS. A nomogram was created with independent risk factors to predict prognosis of patients with ICC.
RESULTS One hundred and sixty-seven ICC patients were enrolled. Based on the diagnostic cut-off values (spleen density ≤ 45.5 Hounsfield units), 55 (32.9%) patients had DROSD. Kaplan–Meier analysis indicated that patients with DROSD had worse OS and RFS than those without DROSD (P < 0.05). Cox regression analysis revealed that DROSD, carcinoembryonic antigen level, carbohydrate antigen 19-9 level, length of hospital stay, lymph node metastasis, and postoperative complications were independent predictors for OS (P < 0.05). The nomogram created with these factors was able to predict the prognosis of patients with ICC with good reliability (OS C-index = 0.733). The area under the curve for OS was 0.79.
CONCLUSION ICC patients with DROSD have worse OS and RFS. The nomogram is a simple and practical method to identify high-risk ICC patients with poor prognosis.
Collapse
Affiliation(s)
- Li-Ming Deng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Yi Wang
- Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Jin-Huan Yang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Jia-Liang Li
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Zi-Yan Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Wen-Ming Bao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Kai-Yu Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Xin-Fei Yao
- Division of Clinical Medicine, First School of Clinical Medicine,Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Chong-Ming Zheng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Jiu-Yi Zheng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Zheng-Ping Yu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Bin Jin
- Department of Hepatobiliary Surgery, Qilu Hospital Shandong University, Jinan 250012, Shandong Province, China
| | - Gang Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| |
Collapse
|