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Pan S, Lu C, Lu H, Zhang H. Prognostic correlation analysis of colorectal cancer patients based on monocyte to lymphocyte ratio and folate receptor-positive circulating tumor cells and construction of a machine learning survival prediction models. Front Oncol 2025; 15:1531836. [PMID: 40376588 PMCID: PMC12078166 DOI: 10.3389/fonc.2025.1531836] [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: 11/21/2024] [Accepted: 04/08/2025] [Indexed: 05/18/2025] Open
Abstract
Purpose To evaluate the prognostic value of the monocyte to lymphocyte ratio (MLR) and folate receptor-positive circulating tumor cells (FR+CTCs) in patients with colorectal cancer (CRC) and to develop predictive model for post-treatment survival using machine learning (ML) algorithms. Methods We retrospectively analyzed 67 CRC patients treated with radical surgery or chemoradiotherapy at The Central Hospital of Wuhan from January 2020 to December 2022. MLR, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and FR+CTCs were categorized into high and low groups and clinicopathologic features were compared. Progression-Free Survival (PFS) and Overall Survival (OS) were analyzed using COX analysis and the Kaplan-Meier survival curve. Three ML algorithms, namely, random forest (RF), support vector machine (SVM), and logistic regression (LR), were utilized to construct the predictive models, and their performance metrics including accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), precision, recall, F1 value, AUC, and calibration curve were compared. Results MLR, FR+ CTCs, and T stage independently predicted PFS (P<0.05), both higher MLR and FR+CTCs levels indicating a significantly shorter PFS (P=0.004). The T stage was the only factor predictive of OS (P=0.043). NLR and PLR did not show significant prognostic effects on PFS or OS (P > 0.05). The RF model demonstrated superior performance with an accuracy of 0.63, sensitivity of 0.69, PPV of 0.75, a precision of 0.43, a recall of 0.5, and an F1 value of 0.43, outperforming the other models. Conclusion High MLR and high FR+CTCs are associated with a poorer PFS in CRC patients, suggesting their utility in prognostic assessment. NLR and PLR did not show significant prognostic value in this study. The RF algorithm-based model showed the best predictive performance for post-radical treatment outcomes in CRC.
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Affiliation(s)
- Siying Pan
- Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chi Lu
- Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Intestinal Microecological Diagnostics, Therapeutics, and Clinical Translation, Wuhan, China
| | - Hongda Lu
- Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Intestinal Microecological Diagnostics, Therapeutics, and Clinical Translation, Wuhan, China
| | - Hongfeng Zhang
- Department of Pathology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Saidi K, Abderrahman AB, Laher I, Hackney AC, Hage RE, Saeidi A, Bideau B, Granacher U, Zouhal H. Immune inflammation markers and physical fitness during a congested match play period in elite male soccer players. Sci Rep 2024; 14:30312. [PMID: 39639055 PMCID: PMC11621450 DOI: 10.1038/s41598-024-81225-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Accepted: 11/25/2024] [Indexed: 12/07/2024] Open
Abstract
BACKGROUND/OBJECTIVE Cellular immune markers of inflammation such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune inflammation index (SII) are frequently used in patient care. The adoption of these markers to elite sports, e.g. soccer could be beneficial when monitoring training and aiming to maximize physical fitness. This study investigated cellular immune inflammation markers and physical fitness in elite male soccer players in relation to changes in training and match exposure during a congested match play period. METHODS Fifteen elite male soccer players were evaluated three times (T1, T2, and T3) over 12 weeks (T1-T2: six weeks uncongested period of match play and T2-T3: six weeks congested period of match play). Players performed vertical jump tests (squat jumps [SJ], countermovement jumps [CMJ]), the 20-meter sprint test, and the Yo-Yo intermittent recovery test (YYIRL1) at T1, T2 and T3. Measurements included counts of leucocytes and its subtypes, as well as platelets. Cellular immune inflammation markers (NLR, PLR and SII) were calculatedat T1, T2, and T3. Training session rating of perceived exertion was also recorded on a daily basis. RESULTS Significant increases in leucocyte, neutrophil, eosinophil, basophil and monocyte counts occurred at T3 compared with T2 (0.002 < p < 0.04, -0.56 < ES < -0.40) and T1 (-0.78 < ES < -0.49). Lymphocyte counts were lower at T3 as compared to T2 and T1 (p = 0.038, -0.48 < ES <-0.25), while NLR, PLR and SII were greater at T3 compared to T2 (0.001 < p < 0.015, -1.01 < ES < -0.44) and T1 (-0.99 < ES < -0.21). There was a negative correlation between YYIRL1 performance with NLR (r= -0.56; p = 0.02), PLR (r=-0,44, p = 0.015), and SII (r= -0.63; p = 0.01) after the congested period of match play (i.e., T3). Values for maximal oxygen uptake (VO2max), estimated from the YYIRL1 test, negatively correlated with NLR (r= -0.56; p = 0.02), PLR (r=-0,44, p = 0.015), and SII (p = 0.01; r= -0.63). There was a positive correlation between NLR, and SII with workload parameters. In addition, a clear positive correlation was observed between NLR and SII with competitive loadinstead (r= [0.59-0.64; p˂ 0.001), training load (TL) (r= [0.65-0.68]; p˂ 0.001), session rating of perceived exertion (S-RPE) (r= [0.65-0.68]; p = 0.001), and training volume (r= [0.60-0.61; p = 0.001). CONCLUSION An intensive period of congested match play significantly alterated immune cell counts and cellular markers of inflammation (NLR, PLR and SII). Changes in NLR and SII were related to workload parameters, suggesting the usefulness of these markers in regulating training intensity and competitive load. An association between physical fitness (YYIRL1, VO2max) and NLR, PLR and SII suggests that these biomarkers are promising tools to monitor aerobic physical fitness of elite soccer players during congested periods of match play.
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Affiliation(s)
- Karim Saidi
- UFR Sciences and Techniques of Physical and Sports Activities, Toulon University, Toulon, France
| | - Abderraouf Ben Abderrahman
- Higher Institute of Sport and Physical Education, Ksar-Said, University of Manouba, Manouba, Tunisia
- Tunisian Research Laboratory "Sport Performance Optimization", National Center of Medicine and Science in Sports, Tunis, Tunisia
| | - Ismail Laher
- Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Vancouver, Canada
| | - Anthony C Hackney
- Department of Exercise & Sport Science, University of North Carolina, Chapel Hill, NC, USA
| | - Rawad El Hage
- Department of Physical Education, Faculty of Arts and Sciences, University of Balamand, PO Box 100, Tripoli, Lebanon
| | - Ayoub Saeidi
- Department of Physical Education and Sport Sciences, Faculty of Humanities and Social Sciences, University of Kurdistan, Sanandaj, Kurdistan, Iran
| | - Benoit Bideau
- Movement, Sport, Health and Sciences laboratory (M2S), University of Rennes 2, Rennes, France
| | - Urs Granacher
- Department of Sport and Sport Science, Exercise and Human Movement Science, University of Freiburg, Freiburg, Germany.
| | - Hassane Zouhal
- Movement, Sport, Health and Sciences laboratory (M2S), University of Rennes 2, Rennes, France.
- Institut International des Sciences du Sport (2I2S), Irodouer, 35850, France.
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Funamizu N, Mori S, Sakamoto A, Iwata M, Shine M, Ito C, Uraoka M, Ueno Y, Tamura K, Umeda Y, Aoki T, Takada Y. C-Reactive Protein-to-Albumin Ratio as a Predictive Indicator for Evaluating Tolerability in S-1 Adjuvant Chemotherapy after Curative Surgery for Pancreatic Cancer: An External Validation Cohort Study. Cancers (Basel) 2024; 16:3372. [PMID: 39409992 PMCID: PMC11475895 DOI: 10.3390/cancers16193372] [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: 09/02/2024] [Revised: 09/26/2024] [Accepted: 09/30/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND S-1 in adjuvant chemotherapy (AC) administration after pancreatic cancer (PC) surgery has been standardized in Japan. The Ehime study confirmed that a postoperative higher C-reactive protein-to-albumin ratio (CAR) value predicted the risk of adverse event (AE)-related S-1 non-completion as an AC in patients with PC after curative surgery. This study aimed to investigate the index to predict S-1 tolerance among patients who underwent curative surgery for PC (the Dokkyo study). METHODS This retrospective validation cohort study included 172 patients at the Department of Hepato-Biliary Pancreatic Surgery, Dokkyo Medical University, Japan, from January 2010 to December 2022. All patients underwent nutritional screening using the postoperative CAR. S-1 completion status and its effect on prognosis were systematically followed up and investigated. We conducted a statistical analysis of predictive markers to investigate their association with S-1 completion. RESULTS Patients were categorized into the S-1 completion (N = 91) and non-completion (N = 81) groups. The S-1 completion group demonstrated a significantly lower CAR than the S1 non-completion group. Moreover, the current study revealed a significant difference in the S-1 completion rate, applying the CAR cutoff value of 0.05 established in the Ehime study. Additionally, univariate and multivariate analyses confirmed that a CAR of <0.05 was significantly associated with S-1 completion. CONCLUSIONS The Dokkyo study confirmed the results observed in the Ehime study. Consequently, an increased postoperative CAR value appeared as a universal applicable marker for the risk factor of AE-related S-1 non-completion after curative surgery for patients with PC.
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Affiliation(s)
- Naotake Funamizu
- Department of Hepato-Biliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon 791-0295, Ehime, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.U.); (Y.T.)
| | - Shozo Mori
- Department of Hepato-Biliary Pancreatic Surgery, Dokkyo Medical University, Kitakobayashi 880, Mibu, Shimotsugagun 321-0293, Tochigi, Japan; (S.M.); (T.A.)
| | - Akimasa Sakamoto
- Department of Hepato-Biliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon 791-0295, Ehime, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.U.); (Y.T.)
| | - Miku Iwata
- Department of Hepato-Biliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon 791-0295, Ehime, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.U.); (Y.T.)
| | - Mikiya Shine
- Department of Hepato-Biliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon 791-0295, Ehime, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.U.); (Y.T.)
| | - Chihiro Ito
- Department of Hepato-Biliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon 791-0295, Ehime, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.U.); (Y.T.)
| | - Mio Uraoka
- Department of Hepato-Biliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon 791-0295, Ehime, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.U.); (Y.T.)
| | - Yoshitomo Ueno
- Department of Hepato-Biliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon 791-0295, Ehime, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.U.); (Y.T.)
| | - Kei Tamura
- Department of Hepato-Biliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon 791-0295, Ehime, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.U.); (Y.T.)
| | - Yuzo Umeda
- Department of Hepato-Biliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon 791-0295, Ehime, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.U.); (Y.T.)
| | - Taku Aoki
- Department of Hepato-Biliary Pancreatic Surgery, Dokkyo Medical University, Kitakobayashi 880, Mibu, Shimotsugagun 321-0293, Tochigi, Japan; (S.M.); (T.A.)
| | - Yasutsugu Takada
- Department of Hepato-Biliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon 791-0295, Ehime, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.U.); (Y.T.)
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Zhang H, Tang X, Zhang J, Jiang D, Gong D, Fan Y. Serum prealbumin level as a biomarker of survival outcomes in patients with gastric cancer: a meta-analysis. Biomarkers 2024; 29:410-417. [PMID: 39268816 DOI: 10.1080/1354750x.2024.2402419] [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: 04/29/2024] [Accepted: 08/31/2024] [Indexed: 09/15/2024]
Abstract
BACKGROUND Previous studies have reported inconsistent results on the association between serum prealbumin level and survival outcomes in patients with gastric cancer. This meta-analysis aimed to determine the serum prealbumin level as a biomarker of survival outcomes in gastric cancer patients. METHODS Two independent reviewers conducted a thorough search of PubMed, Embase, and Web of Science databases until April 17, 2024. Studies reporting the association between serum prealbumin level and survival outcomes and presented the multivariable-adjusted relative risks for gastric cancer patients were included. The pooled HR and 95% CI were used to assess the strength of the association. RESULTS Twelve studies, with a total of 9,351 patients were included in the meta-analysis. The combined data showed that low serum prealbumin level was associated with shorter overall survival (HR 1.65; 95% CI 1.42-1.91) and disease-free survival (HR 1.39; 95% CI 1.14-1.70). Subgroup analysis showed that low serum prealbumin level significantly predicted poorer overall survival, regardless of patients' age, sample sizes, cutoff value for prealbumin level, and follow-up time. CONCLUSIONS Low serum prealbumin level is an independent prognostic biomarker for shorter survival outcomes in patients with gastric cancer. Assessing serum prealbumin levels could potentially improve risk stratification for this disease.
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Affiliation(s)
- Heng Zhang
- Department of General Surgery, Nanjing Lishui District People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, China
| | - Xuan Tang
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China
| | - Junfang Zhang
- Department of Medical Nutrition, Nanjing Lishui District People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, China
| | - Dapeng Jiang
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China
| | - Dandan Gong
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China
| | - Yu Fan
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China
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Zhang X, Huang JX, Tang M, Zhang Q, Deng L, Song CH, Li W, Yang M, Shi HP, Cong MH. A comprehensive analysis of the association between anemia and systemic inflammation in older patients with cancer. Support Care Cancer 2023; 32:39. [PMID: 38110562 DOI: 10.1007/s00520-023-08247-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Accepted: 12/08/2023] [Indexed: 12/20/2023]
Abstract
PURPOSE Our study aimed to comprehensively analyze the association between anemia and systemic inflammation in older patients with cancer. METHODS This multicenter prospective cohort study included 4955 older patients with cancer between 2013 and 2020. Logistic regression analysis was performed to investigate risk factors of anemia, reporting odds ratios (ORs), and 95% confidence intervals (CIs). Comprehensive survival analyses, including Kaplan-Meier curve, Cox proportional risk model, and subgroup analysis, were performed. RESULTS The participants' median age was 70.0 (interquartile range [IQR]=67.0-74.0) years, with 3293 (66.5%) males and 1662 (33.5%) females. There were 1717 (34.7%) older patients with cancer diagnosed with anemia. High neutrophil-to-lymphocyte ratio (NLR) was an independent risk factor associated with anemia (adjusted OR=1.97, 95%CI=1.73-2.24, P<0.001). In older patients with cancer and different anemia levels, the median overall survival was significantly shorter in those with a high NLR. In multivariate Cox analysis, high NLR served as a negative factor, independently affecting survival. The anemia-inflammation prognostic grading system showed a significant survival discriminative performance in older patients with cancer. After adjusting for confounders, high grades were independent risk factors for survival (grade 2: hazard ratio [HR] = 1.38, 95%CI = 1.26-1.52, P<0.001; grade 3: HR=1.82 95%CI = 1.59-2.09, P<0.001). This grading system was beneficial in determining survival in patients with lung, digestive tract, and urogenital cancers. CONCLUSIONS Increased systemic inflammation is an independent risk factor for anemia. A high inflammatory status is also associated with poor survival in older cancer patients at different anemia levels. The anemia-inflammation grading system is beneficial for determining the prognosis in older patients with cancer.
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Affiliation(s)
- Xi Zhang
- Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
| | - Jia-Xin Huang
- Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Cancer Center of the First Hospital of Jilin University, Changchun, 130021, People's Republic of China
| | - Meng Tang
- Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
| | - Qi Zhang
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
- Department of Gastrointestinal Surgery, Zhejiang Cancer Hospital, Zhejiang, China
| | - Li Deng
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Chun-Hua Song
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Wei Li
- Cancer Center of the First Hospital of Jilin University, Changchun, 130021, People's Republic of China
| | - Min Yang
- Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Han-Ping Shi
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, China.
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China.
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
| | - Ming-Hua Cong
- Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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Sturgeon R, Goel P, Singh RK. Tumor-associated neutrophils in pancreatic cancer progression and metastasis. Am J Cancer Res 2023; 13:6176-6189. [PMID: 38187037 PMCID: PMC10767342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Accepted: 11/22/2023] [Indexed: 01/09/2024] Open
Abstract
Pancreatic cancer (PC) remains a challenge to modern-day cancer therapeutics, with a dismal five-year survival rate of 12%. Due to the pancreas's location and desmoplasia surrounding it, patients receive late diagnoses and fail to respond to chemotherapy regimens. Tumor-promoting inflammation, one of the emerging hallmarks of cancer, contributes to tumor cells' survival and proliferation. This inflammation often results from infiltrating leukocytes and pro-inflammatory cytokines released into the tumor microenvironment (TME). Neutrophils, one of our body's most prominent immune cells, are essential in sustaining the inflammation observed in the TME. Recent reports demonstrate that neutrophils are complicit in cancer progression and metastasis. Additionally, abundant data suggest that tumor-associated neutrophils (TANs) could be considered as one of the emerging targets for multiple cancer types, including PC. This review will focus on the most recent updates regarding neutrophil recruitments and functions in the cancer microenvironment and the potential development of neutrophils-targeted putative therapeutic strategies in PC.
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Affiliation(s)
- Reegan Sturgeon
- Department of Pathology and Microbiology, The University of Nebraska Medical Center985845 UNMC, Omaha, NE 68198-5845, USA
| | - Paran Goel
- The University of AlabamaBirmingham, AL 35294-1210, USA
| | - Rakesh K Singh
- Department of Pathology and Microbiology, The University of Nebraska Medical Center985845 UNMC, Omaha, NE 68198-5845, USA
- Department of Pathology and Microbiology, The University of Nebraska Medical Center, 985900 Nebraska Medical CenterOmaha, NE 68198-5900, USA
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Kim S, Joo M, Yeo MK, Cho MJ, Kim JS, Jo EK, Kim JM. Small heterodimer partner as a predictor of neoadjuvant radiochemotherapy response and survival in patients with rectal cancer: A preliminary study. Oncol Lett 2021; 22:708. [PMID: 34457063 PMCID: PMC8358587 DOI: 10.3892/ol.2021.12969] [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: 03/31/2020] [Accepted: 06/16/2021] [Indexed: 11/06/2022] Open
Abstract
Small heterodimer partner (SHP) plays an essential role in the regulation of innate immune and inflammatory responses. The aim of the present study was to identify whether SHP levels are associated with cancer immunology and treatment outcomes in rectal cancer. SHP expression was analyzed via gene set enrichment analysis and the OncoLnc database. In addition, immunohistochemistry and reverse transcription-quantitative PCR analyses were performed on the tissues of patients with locally advanced rectal cancer, and the associations of SHP expression with the clinicopathological and hematological features or treatment response to preoperative radiochemotherapy (pRCT) were analyzed retrospectively. Furthermore, the present study investigated whether SHP expression correlated with immune infiltration levels and immune checkpoint molecules in rectal cancer. The results revealed that low SHP mRNA expression was significantly associated with an inflammatory response and poor prognosis. The nuclear expression of SHP was associated with clinical N stage, neutrophil count, lymphocyte count, neutrophil-lymphocyte ratio and complete pathologic response following pRCT. The low nuclear expression of SHP was associated with poor overall and distant metastasis-free survival (DMFS). In multivariate analysis, the low nuclear expression of SHP was identified as a significant independent prognostic factor for DMFS and a marginally significant prognostic factor for overall survival in rectal cancer. Furthermore, patients with low SHP expression exhibited higher neutrophil and CD8+ T cell infiltration levels and higher PD-L1 expression in rectal adenocarcinoma. These results indicate that SHP may act as an anti-inflammatory mediator via the regulation of systemic and local immune responses in rectal cancer. Moreover, SHP might be useful a potential marker or therapeutic target in rectal cancer.
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Affiliation(s)
- Sup Kim
- Department of Radiation Oncology, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea
| | - Mina Joo
- Department of Pathology and Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea
| | - Min-Kyung Yeo
- Department of Pathology and Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea
| | - Moon-June Cho
- Department of Radiation Oncology, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea
| | - Jun-Sang Kim
- Department of Radiation Oncology, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea
| | - Eun-Kyeong Jo
- Department of Microbiology and Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.,Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea
| | - Jin-Man Kim
- Department of Pathology and Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.,Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea
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Siqueira JM, Soares JDP, Borges TC, Gomes TLN, Pimentel GD. High neutrophil to lymphocytes ratio is associated with nutritional risk in hospitalised, unselected cancer patients: a cross-sectional study. Sci Rep 2021; 11:17120. [PMID: 34429466 PMCID: PMC8384836 DOI: 10.1038/s41598-021-96586-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 08/12/2021] [Indexed: 02/06/2023] Open
Abstract
Cancer patients possess metabolic and pathophysiological changes and an inflammatory environment that leads to malnutrition. This study aimed to (i) determine whether there is an association between neutrophil-to-lymphocyte ratio (NLR) and nutritional risk, and (ii) identify the cut-off value of NLR that best predicts malnutrition by screening for nutritional risk (NRS 2002). This cross-sectional study included 119 patients with unselected cancer undergoing chemotherapy and/or surgery. The NRS 2002 was applied within 24 h of hospitalisation to determine the nutritional risk. Systemic inflammation was assessed by blood collection, and data on C-reactive protein (CRP), neutrophils, and lymphocytes were collected for later calculation of NLR. A receiver operating characteristic (ROC) curve was used to identify the best cut-point for NLR value that predicted nutritional risk. Differences between the groups were tested using the Student's t-, Mann-Whitney U and Chi-Square tests. Logistic regression analyses were performed to assess the association between NLR and nutritional risk. The ROC curve showed the best cut-point for predicting nutritional risk was NLR > 5.0 (sensitivity, 60.9%; specificity, 76.4%). The NLR ≥ 5.0 group had a higher prevalence of nutritional risk than the NLR < 5.0 group (NLR ≥ 5.0: 73.6% vs. NLR < 5.0: 37.9%, p = 0.001). The NLR group ≥ 5.0 showed higher values of CRP and NLR than the NLR < 5.0 group. In addition, patients with NLR ≥ 5.0 also had higher NRS 2002 values when compared to the NLR < 5.0 group (NLR ≥ 5.0: 3.0 ± 1.1 vs. NLR < 5.0: 2.3 ± 1.2, p = 0.0004). Logistic regression revealed an association between NRS and NLR values. In hospitalised unselected cancer patients, systemic inflammation measured by NLR was associated with nutritional risk. Therefore, we highlight the importance of measuring the NLR in clinical practice, with the aim to detect nutritional risk.
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Affiliation(s)
- Jéssika M Siqueira
- Faculty of Nutrition, Federal University of Goiás, Rua 227, Quadra 68 s/n°, Setor Leste Universitário, Goiânia, GO, 74605080, Brasil
| | - Jéssika D P Soares
- Faculty of Nutrition, Federal University of Goiás, Rua 227, Quadra 68 s/n°, Setor Leste Universitário, Goiânia, GO, 74605080, Brasil
| | - Thaís C Borges
- Faculty of Nutrition, Federal University of Goiás, Rua 227, Quadra 68 s/n°, Setor Leste Universitário, Goiânia, GO, 74605080, Brasil
| | - Tatyanne L N Gomes
- Faculty of Nutrition, Federal University of Goiás, Rua 227, Quadra 68 s/n°, Setor Leste Universitário, Goiânia, GO, 74605080, Brasil
| | - Gustavo D Pimentel
- Faculty of Nutrition, Federal University of Goiás, Rua 227, Quadra 68 s/n°, Setor Leste Universitário, Goiânia, GO, 74605080, Brasil.
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9
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Du S, Fang Z, Ye L, Sun H, Deng G, Wu W, Zeng F. Pretreatment neutrophil-to-lymphocyte ratio predicts the benefit of gastric cancer patients with systemic therapy. Aging (Albany NY) 2021; 13:17638-17654. [PMID: 34245559 PMCID: PMC8312446 DOI: 10.18632/aging.203256] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 06/18/2021] [Indexed: 01/30/2023]
Abstract
Pretreatment neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with the prognosis of inoperable gastric cancer patients with systemic therapy. However, no consensus on the association has been reached. In this study, we mainly evaluated whether pretreatment NLR predicted the benefit of inoperable gastric cancer patients with systemic therapy, including chemotherapy, targeted therapy and immunotherapy. PubMed, Embase and Cochrane Library databases were systematically searched from inception up to September 16th, 2020. A total of 36 studies including 8614 patients were involved in the meta-analysis. Pooled data revealed that high pretreatment NLR was significantly associated with poor outcomes of OS (HR = 1.78, 95% CI = [1.59, 1.99]) and PFS (HR = 1.63, 95% CI = [1.39, 1.91]) in gastric cancer. Subgroup analyses stratified by country, study type, case load, analysis of HR, cutoff of pretreatment NLR, or treatment types arrived at the same conclusion. Pooled data based on different effect models and sensitivity analyses did not change the conclusion. Overall, high pretreatment NLR predicts the poor prognosis of inoperable gastric cancer patients with systemic therapy. Measurement of pretreatment NLR will assist clinicians with patient counseling and clinical treatment guiding accordingly.
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Affiliation(s)
- Songtao Du
- Department of Oncology and Geratic Surgery, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Colorectal Surgical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
- Department of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zhenhao Fang
- Department of Oncology and Geratic Surgery, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Lin Ye
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Huiyan Sun
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Guangtong Deng
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Wei Wu
- Department of Oncology and Geratic Surgery, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Furong Zeng
- Department of Oncology and Geratic Surgery, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China
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Qian C, Cai R, Zhang W, Wang J, Hu X, Zhang Y, Jiang B, Yuan H, Liu F. Neutrophil-Lymphocyte Ratio and Circulating Tumor Cells Counts Predict Prognosis in Gastrointestinal Cancer Patients. Front Oncol 2021; 11:710704. [PMID: 34307180 PMCID: PMC8293392 DOI: 10.3389/fonc.2021.710704] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 06/18/2021] [Indexed: 12/16/2022] Open
Abstract
Purpose The purpose of this study is to explore the prognostic value of associating pre-treatment neutrophil–lymphocyte ratio (NLR) with circulating tumor cells counts (CTCs) in patients with gastrointestinal cancer. Materials and Methods We collected the related data of 72 patients with gastric cancer (GC) and colorectal cancer (CRC) who received different therapies from August 2016 to October 2020, including age, gender, primary tumor location, TNM stage, tumor-differentiation, NLR, CTCs, disease-free survival (DFS) and overall survival (OS). We chose the optimal cut-off value of NLR >3.21 or NLR ≤3.21 and CTC >1 or CTC ≤1 by obtaining receiver operating characteristic (ROC) curve. The Kaplan–Meier survival analysis and Cox regression analysis were used to analyze DFS and OS. To clarify the role of the combination of NLR and CTCs counts in predicting the prognosis, we analyzed the DFS and OS when associated NLR and CTCs counts. Results A high NLR (>3.21) was associated with shorter DFS (P <0.0001) and OS (P <0.0001). Patients with high CTCs level (>1) had shorter DFS (P = 0.001) and OS (P = 0.0007) than patients with low CTCs level. Furthermore, patients who had both higher NLR and higher CTCs counts had obvious shorter DFS (P <0.0001) and OS (P <0.0001). Conclusions Patients with higher NLR and more CTCs respectively tended to have poor prognosis with shorter DFS and OS, which might be regarded as predictors of gastrointestinal cancer. In particular, associating NLR and CTCs counts might be a reliable predictor in patients with gastrointestinal cancer.
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Affiliation(s)
- Chengcheng Qian
- Department of Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Renjie Cai
- Department of Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wenying Zhang
- Department of Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiongyi Wang
- Department of Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaohua Hu
- Department of Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yanjie Zhang
- Department of Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bin Jiang
- Department of Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Haihua Yuan
- Department of Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Feng Liu
- Department of Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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11
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Walzik D, Joisten N, Zacher J, Zimmer P. Transferring clinically established immune inflammation markers into exercise physiology: focus on neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and systemic immune-inflammation index. Eur J Appl Physiol 2021; 121:1803-1814. [PMID: 33787989 PMCID: PMC8192383 DOI: 10.1007/s00421-021-04668-7] [Citation(s) in RCA: 70] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 03/16/2021] [Indexed: 02/07/2023]
Abstract
Over the last decades the cellular immune inflammation markers neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII = NLR × platelets) have emerged in clinical context as markers of disease-related inflammation and are now widely appreciated due to their integrative character. Transferring these clinically established inflammation markers into exercise physiology seems highly beneficial, especially due to the low temporal, financial and infrastructural resources needed for assessment and calculation. Therefore, the aim of this review is to summarize evidence on the value of the integrative inflammation markers NLR, PLR and SII for depiction of exercise-induced inflammation and highlight potential applications in exercise settings. Despite sparse evidence, multiple investigations revealed responsiveness of the markers to acute and chronic exercise, thereby opening promising avenues in the field of exercise physiology. In performance settings, they might help to infer information for exercise programming by reflecting exercise strain and recovery status or periods of overtraining and increased infection risk. In health settings, application involves the depiction of anti-inflammatory effects of chronic exercise in patients exhibiting chronic inflammation. Further research should, therefore, focus on establishing reference values for these integrative markers in athletes at rest, assess the kinetics and reliability in response to different exercise modalities and implement the markers into clinical exercise trials to depict anti-inflammatory effects of chronic exercise in different patient collectives.
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Affiliation(s)
- David Walzik
- Institute for Sport and Sport Science, TU Dortmund University, Dortmund, Germany
| | - Niklas Joisten
- Institute for Sport and Sport Science, TU Dortmund University, Dortmund, Germany
| | - Jonas Zacher
- Institute for Cardiovascular Research and Sport Medicine, German Sport University Cologne, Cologne, Germany
| | - Philipp Zimmer
- Institute for Sport and Sport Science, TU Dortmund University, Dortmund, Germany.
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12
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Munir H, Jones JO, Janowitz T, Hoffmann M, Euler M, Martins CP, Welsh SJ, Shields JD. Stromal-driven and Amyloid β-dependent induction of neutrophil extracellular traps modulates tumor growth. Nat Commun 2021; 12:683. [PMID: 33514748 PMCID: PMC7846803 DOI: 10.1038/s41467-021-20982-2] [Citation(s) in RCA: 104] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 12/17/2020] [Indexed: 02/07/2023] Open
Abstract
Tumors consist of cancer cells and a network of non-cancerous stroma. Cancer-associated fibroblasts (CAF) are known to support tumorigenesis, and are emerging as immune modulators. Neutrophils release histone-bound nuclear DNA and cytotoxic granules as extracellular traps (NET). Here we show that CAFs induce NET formation within the tumor and systemically in the blood and bone marrow. These tumor-induced NETs (t-NETs) are driven by a ROS-mediated pathway dependent on CAF-derived Amyloid β, a peptide implicated in both neurodegenerative and inflammatory disorders. Inhibition of NETosis in murine tumors skews neutrophils to an anti-tumor phenotype, preventing tumor growth; reciprocally, t-NETs enhance CAF activation. Mirroring observations in mice, CAFs are detected juxtaposed to NETs in human melanoma and pancreatic adenocarcinoma, and show elevated amyloid and β-Secretase expression which correlates with poor prognosis. In summary, we report that CAFs drive NETosis to support cancer progression, identifying Amyloid β as the protagonist and potential therapeutic target.
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Affiliation(s)
- Hafsa Munir
- MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Box 197 Cambridge Biomedical Campus, Cambridge, CB2 0XZ, England
| | - James O Jones
- MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Box 197 Cambridge Biomedical Campus, Cambridge, CB2 0XZ, England
- Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ, England
| | - Tobias Janowitz
- Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY, 11724, USA
- Northwell Health Cancer Institute, New York, NY, 11021, USA
- Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK
| | - Markus Hoffmann
- Friedrich Alexander University Erlangen-Nuremberg, Universitätsklinikum Erlangen, Department of Medicine 3, Universitätsstrasse 25a, 91054, Erlangen, Germany
| | - Maximilien Euler
- Friedrich Alexander University Erlangen-Nuremberg, Universitätsklinikum Erlangen, Department of Medicine 3, Universitätsstrasse 25a, 91054, Erlangen, Germany
| | - Carla P Martins
- MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Box 197 Cambridge Biomedical Campus, Cambridge, CB2 0XZ, England
- Early Oncology TDE, Oncology R&D, AstraZeneca, Cambridge, CB2 0RE, England
| | - Sarah J Welsh
- Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ, England
- Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK
| | - Jacqueline D Shields
- MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Box 197 Cambridge Biomedical Campus, Cambridge, CB2 0XZ, England.
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13
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Li Q, Huang LY, Xue HP. Comparison of prognostic factors in different age groups and prognostic significance of neutrophil-lymphocyte ratio in patients with gastric cancer. World J Gastrointest Oncol 2020; 12:1146-1166. [PMID: 33133383 PMCID: PMC7579735 DOI: 10.4251/wjgo.v12.i10.1146] [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: 06/04/2020] [Revised: 08/04/2020] [Accepted: 09/02/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) is one of the most common malignant tumors in the world. Although in recent years tremendous progress has been made in its early detection, the postoperative overall survival (OS) of GC patients remains extremely low. A number of studies have shown that age, to varying degrees, affects the prognosis of patients with GC. Therefore, this study retrospectively analyzed the clinical and pathologic data of patients with GC to explore the differences in the clinical characteristics and prognostic factors in different age groups.
AIM To explore the difference in clinicopathological characteristics and prognostic factors in GC patients in different age groups.
METHODS In this retrospective study, we analyzed 1037 GC patients admitted to Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from May 2010 to January 2013. The patients were divided into two groups based on age: Younger group (less than 70 years old) and older group (no less than 70 years old). In the younger group, we subdivided the patients in two subgroups by a cut-off value of 45 years. The clinical features and prognostic factors were analyzed in both groups. Subsequently, we retrieved studies that evaluated the predictive role of neutrophil-lymphocyte ratio (NLR) by searching two medical databases, PubMed and EMBASE, to conduct a meta-analysis. Random-effects model was used to pool the data.
RESULTS In the retrospective study, the mean OS time of the younger group (64.7 mo) was significantly longer than that of the older group (48.1 mo) (P < 0.001). Among patients under 70 years of age, hospitalization time, tumor–node–metastasis (TNM) stage, vascular invasion, and preoperative low pre-albumin were independently associated with OS (P < 0.005). In patients aged 70 years and above, TNM stage, esophageal invasion, histological type, and preoperative NLR were independent factors for OS (P < 0.05). The OS of these older patients was also significantly shorter (P < 0.05). In the meta-analysis, 19 retrieved studies included a total of 8312 patients, among whom 3558 had elevated NLR values. The results showed that high NLR value was a risk factor for the prognosis of GC (P < 0.01).
CONCLUSION The OS of elderly patients is significantly worse than that of younger patients. There are significant differences in clinicopathological characteristics and prognostic factors between younger and older patients. NLR is a convenient, inexpensive, and reproducible marker that can be used as an important predictor of the prognosis of GC.
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Affiliation(s)
- Qiong Li
- Department ofGastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
| | - Lin-Yi Huang
- Department ofGastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
| | - Hui-Ping Xue
- Department ofGastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
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14
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Zang S, Shi L, Zhao J, Yang M, Liu J, Ding H. Prealbumin to fibrinogen ratio is closely associated with diabetic peripheral neuropathy. Endocr Connect 2020; 9:858-863. [PMID: 32880377 PMCID: PMC7487192 DOI: 10.1530/ec-20-0316] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Accepted: 08/06/2020] [Indexed: 12/22/2022]
Abstract
The aim of our study was to explore the diagnostic value of prealbumin to fibrinogen ratio (PFR) for predicting prognosis with the optimal cut-off value in diabetic peripheral neuropathy (DPN) patients. A total of 568 type 2 diabetes mellitus (T2DM) patients were enrolled in this study. The values including Toronto clinical neuropathy score (TCNS), nerve conduction velocity (NCV), vibration perception threshold (VPT), blood cells count, biochemical parameters, fibrinogen and PFR were recorded. The patients were divided into tertiles based on admission PFR value. First, clinical parameters were compared among the groups. Secondly, a logistic regression and ROC analysis were performed as the statistical model. The percentage of DPN, TCNS and VPT were significantly higher in the lowest PFR tertile than in the middle PFR tertile and the highest PFR tertile (P < 0.01-0.001). NCV was significantly lower in lowest PFR tertile than in the middle PFR tertile and the highest PFR tertile (P < 0.01-0.001). The Spearman correlation analysis showed that PFR was negatively correlated with TCNS and VPT (P < 0.001), while PFR was positively correlated with median motor NCV (P < 0.001), peroneal motor NCV (P < 0.001), median sensory NCV (P < 0.001), and peroneal sensory NCV (P < 0.001). After adjusting these potentially related factors, PFR was independently related to DPN (P = 0.007). The area under ROC curve was 0.627. This study finds the first evidence to suggest PFR may be the key component associated with DPN in T2DM, while PFR might underlie the pathophysiologic features of DPN.
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Affiliation(s)
- Shufei Zang
- Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
| | - Lei Shi
- Department of Neurology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
| | - Jinying Zhao
- Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
| | - Min Yang
- Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
| | - Jun Liu
- Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
| | - Heyuan Ding
- Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
- Correspondence should be addressed to H Ding:
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15
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Profiles Combining Muscle Atrophy and Neutrophil-to-Lymphocyte Ratio Are Associated with Prognosis of Patients with Stage IV Gastric Cancer. Nutrients 2020; 12:nu12061884. [PMID: 32599747 PMCID: PMC7353220 DOI: 10.3390/nu12061884] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 06/14/2020] [Accepted: 06/20/2020] [Indexed: 12/13/2022] Open
Abstract
We aimed to investigate the impact of muscle atrophy and the neutrophil-to-lymphocyte ratio (NLR), a sub-clinical biomarker of inflammation and nutrition, on the prognosis of patients with unresectable advanced gastric cancer. We retrospectively enrolled 109 patients with stage IV gastric cancer (median age 69 years; female/male 22%/78%; median observational period 261 days). Independent factors and profiles for overall survival (OS) were determined by Cox regression analysis and decision-tree analysis, respectively. OS was calculated using the Kaplan–Meier method. The prevalence of muscle atrophy was 82.6% and the median NLR was 3.15. In Cox regression analysis, none of factors were identified as an independent factor for survival. The decision-tree analysis revealed that the most favorable prognostic profile was non-muscle atrophy (OS rate 36.8%). The most unfavorable prognostic profile was the combination of muscle atrophy and high NLR (OS rate 19.6%). The OS rate was significantly lower in patients with muscle atrophy and high NLR than in patients with non-muscle atrophy (1-year survival rate 28.5% vs. 54.7%; log-rank test p = 0.0014). In conclusion, “muscle atrophy and high NLR” was a prognostic profile for patients with stage IV gastric cancer. Thus, the assessment of muscle mass, subclinical inflammation, and malnutrition may be important for the management of patients with stage IV gastric cancer.
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16
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Yang QK, Su YN, Wang W, Wang N, Yao ZX, Zhang XJ. CONUT Score or/and Peripheral Blood CD4+/CD8+ Ratio-Based Web Dynamic Nomograms to Predict the Individualized Survival of Patients with Advanced Osteosarcoma. Cancer Manag Res 2020; 12:4193-4208. [PMID: 32581591 PMCID: PMC7276395 DOI: 10.2147/cmar.s251814] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 05/10/2020] [Indexed: 12/14/2022] Open
Abstract
Background Nutritional and immune status is paramount for the overall survival (OS) of patients with advanced osteosarcoma. Comprehensive prognostic predictors based on the two indices are scarce. This study aimed to construct and validate individualized web dynamic nomograms based on CONUT score or/and peripheral blood CD4+/CD8+ ratio for OS in patients with advanced osteosarcoma. Materials and Methods The clinical data of 376 advanced osteosarcoma patients from January 2000 to December 2019 were retrospectively collected. Data from the 301 patients (diagnosed in the first 15 years) were used as the development set and data from the remaining 75 patients were assigned as the validation set. Multivariate Cox regression analyses were conducted and three prediction models were constructed, namely, CD4+/CD8+ ratio univariate model (model 1), CONUT score univariate model (model 2), and CD4+/CD8+ ratio plus CONUT score (model 3). These models were visualized by conventional nomograms and individualized web dynamic nomograms, and their performances were further evaluated by C-index, calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA), respectively. Results In multivariate Cox analysis, age, metastasis, ALP, CD4+/CD8+ ratio, chemotherapy, and CONUT score were identified as independent prognostic factors for OS. The calibration curves of the three models all showed good agreement between the actual observation and nomogram prediction for 1-year overall survival. In the development set, the C-index and area under the curve (AUC) of model 3 (0.837, 0.848) were higher than that of model 1 (0.765, 0.773) and model 2 (0.712, 0.749). Similar trends were observed in the validation set. The net benefits of model 3 were better than the other two models within the threshold probability of 36–80% in DCA. Conclusion CONUT score and peripheral CD4+/CD8+ ratio are easily available, reliable, and economical prognostic predictors for survival prediction and stratification in patients with advanced osteosarcoma, but the two predictors combined can establish a better prognosis prediction model.
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Affiliation(s)
- Qian-Kun Yang
- Department of Bone and Soft Tissue Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, People's Republic of China
| | - Yan-Na Su
- Clinical Laboratory, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110042, People's Republic of China
| | - Wei Wang
- Department of Bone and Soft Tissue Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, People's Republic of China
| | - Nan Wang
- Department of Radiotherapy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, People's Republic of China
| | - Zhong-Xiang Yao
- Department of Physiology, Army Medical University, Chongqing 400038, People's Republic of China
| | - Xiao-Jing Zhang
- Department of Bone and Soft Tissue Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, People's Republic of China
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17
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Wu L, Saxena S, Singh RK. Neutrophils in the Tumor Microenvironment. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1224:1-20. [PMID: 32036601 DOI: 10.1007/978-3-030-35723-8_1] [Citation(s) in RCA: 111] [Impact Index Per Article: 22.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Neutrophils are the first responders to inflammation, infection, and injury. As one of the most abundant leukocytes in the immune system, neutrophils play an essential role in cancer progression, through multiple mechanisms, including promoting angiogenesis, immunosuppression, and cancer metastasis. Recent studies demonstrating elevated neutrophil to lymphocyte ratios suggest neutrophil as a potential therapeutic target and biomarker for disease status in cancer. This chapter will discuss the phenotypic and functional changes in the neutrophil in the tumor microenvironment, the underlying mechanism(s) of neutrophil facilitated cancer metastasis, and clinical potential of neutrophils as a prognostic/diagnostic marker and therapeutic target.
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Affiliation(s)
- Lingyun Wu
- Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Sugandha Saxena
- Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Rakesh K Singh
- Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
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18
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Matsunaga T, Miyata H, Sugimura K, Motoori M, Asukai K, Yanagimoto Y, Yamamoto K, Akita H, Nishimura J, Wada H, Takahashi H, Yasui M, Omori T, Ohue M, Fujiwara Y, Yano M. Prognostic Significance of C-reactive Protein-to-prealbumin Ratio in Patients with Esophageal Cancer. Yonago Acta Med 2019; 63:8-19. [PMID: 32158328 DOI: 10.33160/yam.2020.02.002] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Accepted: 11/25/2019] [Indexed: 01/27/2023]
Abstract
Background The prognostic value of combination of C-reactive protein and prealbumin (CRP/PAlb) in esophageal cancer remains unclear. Methods We enrolled 167 esophageal cancer patients who underwent curative esophagectomy. Univariate and multivariate analyses were performed to determine the prognostic significance of various markers, including CRP-to-albumin (CRP/Alb) ratio, modified Glasgow prognostic score, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index. Results Receiver operating characteristic analysis revealed the optimal cut-off value of each inflammatory factor, and CRP/PAlb ratio had the greatest discriminative power in predicting recurrence-free survival (RFS) among the examined measures (AUC 0.668). The 5-year overall survival and RFS rates were significantly lower in patients with high CRP/PAlb ratio than in those with low CRP/PAlb ratio (P < 0.001, P = 0.001, respectively). In the univariate analysis, RFS was significantly worse in patients with low BMI, T2 or deeper tumor invasion, positive lymph node metastasis, positive venous invasion, high CRP/PAlb ratio, high CRP/Alb ratio, high NLR, and high LMR. Multivariate analysis revealed that CRP/PAlb, but not CRP/Alb, was an independent prognostic factor along with lymph node metastasis. Conclusion CRP/PAlb ratio was useful for predicting the prognosis of esophageal cancer patients.
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Affiliation(s)
- Tomoyuki Matsunaga
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan.,Division of Surgical Oncology, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan
| | - Hiroshi Miyata
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Keijiro Sugimura
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Masaaki Motoori
- Department of Surgery, Osaka General Medical Center, Osaka 558-8558, Japan
| | - Kei Asukai
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Yoshitomo Yanagimoto
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Kazuyoshi Yamamoto
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Hirofumi Akita
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Junichi Nishimura
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Hiroshi Wada
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Hidenori Takahashi
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Masayoshi Yasui
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Takeshi Omori
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Masayuki Ohue
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Yoshiyuki Fujiwara
- Division of Surgical Oncology, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan
| | - Masahiko Yano
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan
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C-Reactive Protein to Prealbumin Ratio (CPR): A Novel Inflammatory-Nutritional Prognostic Factor for Predicting Cancer-Specific Survival (CSS) and Overall Survival (OS) in Patients with Resectable Esophageal Squamous Cell Carcinoma. JOURNAL OF ONCOLOGY 2019; 2019:4359103. [PMID: 31379941 PMCID: PMC6662452 DOI: 10.1155/2019/4359103] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Accepted: 06/16/2019] [Indexed: 01/16/2023]
Abstract
Background The inflammation and nutrition play an important role in prognosis. A novel index combined with inflammatory and nutritional biomarkers, named C-reactive protein (CRP) to prealbumin (PALB) ratio (CPR), was initially reported to predict the prognosis in resectable esophageal squamous cell carcinoma (ESCC). Patients and Methods A retrospective study was conducted including 346 resectable ESCC patients. The X-tile program was used to confirm the optimal cut-off value. The Kaplan-Meier methods and Cox regression analyses were performed to analyze the cancer-specific survival (CSS) and overall survival (OS). Results The optimum cut-off point was 0.03 for CPR. Patients with a high level of CPR (> 0.03) were associated with poor CSS (12.0% vs. 43.0%, P<0.001) and OS (11.2% vs. 40.7%, P<0.001). Multivariate analyses revealed that CPR was an independent predictor in resectable ESCC patients (CSS, P=0.008; OS, P=0.007). Conclusion This study, to the best of our knowledge, is the first to investigate prognostic role of CPR in patients with ESCC. Our retrospective observations indicate that CPR, with the optimal cut-off value of 0.03, is a useful potential predictor in resectable ESCC patients.
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Prognostic Value of Pretreatment Serum Transthyretin Level in Patients with Gastrointestinal Cancers. DISEASE MARKERS 2019; 2019:7142065. [PMID: 31275452 PMCID: PMC6589268 DOI: 10.1155/2019/7142065] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 04/18/2019] [Indexed: 01/19/2023]
Abstract
Background Many studies have shown the link between the pretreatment serum transthyretin and prognosis in gastrointestinal (GI) cancers. However, based on the conclusion, the initial findings were inconsistent. Hence, this meta-analysis was performed to identify the prognostic values of the pretreatment serum transthyretin in GI cancers. Methods Previous studies published before November 2018 were collected from a comprehensive literature search of several databases. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were applied in the assessment of the intensity of associations. Also, the publication bias and the robustness of merged data were assessed. All statistical analyses were undertaken using STATA/SE 14.1. Results The combined data indicated that the pretreatment serum transthyretin level was related to the prognosis in GI cancers. The group with reduced pretreatment transthyretin had a significantly worse overall survival (OS) (HR = 1.71, 95% CI: 1.37-2.05). The subgroup analysis for OS further showed the predictive value of transthyretin. In addition, the low serum transthyretin level could be an unfavorable factor for recurrence-free survival (RFS) or progression-free survival (PFS) (HR = 1.66, 95% CI: 1.14-2.18) in GI cancers. Conclusion The low pretreatment serum transthyretin level implies an unfavorable prognosis for patients with GI cancers. The monitoring of pretreatment transthyretin level could contribute to the risk stratification and individualized therapy in GI cancers.
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Lu J, Xu BB, Zheng ZF, Xie JW, Wang JB, Lin JX, Chen QY, Cao LL, Lin M, Tu RH, Huang ZN, Zheng CH, Huang CM, Li P. CRP/prealbumin, a novel inflammatory index for predicting recurrence after radical resection in gastric cancer patients: post hoc analysis of a randomized phase III trial. Gastric Cancer 2019; 22:536-545. [PMID: 30377862 DOI: 10.1007/s10120-018-0892-0] [Citation(s) in RCA: 72] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Accepted: 10/25/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Serum prealbumin (PALB) can predict the prognosis of patients with gastric cancer (GC). However, the prognostic value of combination of C-reactive protein and PALB (CRP/PALB) remains unclear. METHODS A total of 419 gastric cancer patients included in a clinical trial (NCT02327481) were analyzed. The present study is a substudy of the trial. Receiver operating characteristic (ROC) curves were generated, and by calculating the areas under the curve (AUC) and the C-index, the discriminative ability of each inflammatory index was compared, including CRP/PALB, C-reactive protein/albumin, Glasgow prognostic score (GPS), modified GPS, systemic immune-inflammation index, neutrophil-lymphocyte ratio, and platelet-lymphocyte ratio. RESULTS Ultimately, 401 patients were included in this study. The optimal cutoff value of CRP/PALB was 17.7. According to this cutoff point, the entire sample was divided into a CRP/PALB < 17.7 (LCP) group and a CRP/PALB ≥ 17.7 (HCP) group, comprising 245 and 156 patients, respectively. There were 54 and 22 patients experienced recurrence in the HCP and LCP group, respectively, p < 0.001. Compared with traditional inflammatory indices, CRP/PALB had the highest AUC (0.707) and C-index (0.716), all p < 0.05. The post-recurrence survival (PRS) of patients in the HCP group was significantly shorter than that in the LCP group (p = 0.010), especially for pathological stage III patients (p = 0.015) or patients with distant (p = 0.018) or local (p = 0.023) recurrences. CONCLUSIONS The predictive value of preoperative CRP/PALB for the recurrence of GC is significantly better than traditional inflammatory indices. HCP significantly reduces the PRS, especially for pathological stage III patients or patients with distant or local recurrences.
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Affiliation(s)
- Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China
| | - Bin-Bin Xu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China
| | - Zhi-Fang Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China
| | - Jia-Bin Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China
| | - Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China
| | - Long-Long Cao
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China
| | - Mi Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China
| | - Ru-Hong Tu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China
| | - Ze-Ning Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China.
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China.
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China.
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Tumor-Associated Neutrophils in Cancer: Going Pro. Cancers (Basel) 2019; 11:cancers11040564. [PMID: 31010242 PMCID: PMC6520693 DOI: 10.3390/cancers11040564] [Citation(s) in RCA: 235] [Impact Index Per Article: 39.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 04/09/2019] [Accepted: 04/17/2019] [Indexed: 02/07/2023] Open
Abstract
The progression of cancer is not only about the tumor cell itself, but also about other involved players including cancer cell recruited immune cells, their released pro-inflammatory factors, and the extracellular matrix. These players constitute the tumor microenvironment and play vital roles in the cancer progression. Neutrophils—the most abundant white blood cells in the circulation system—constitute a significant part of the tumor microenvironment. Neutrophils play major roles linking inflammation and cancer and are actively involved in progression and metastasis. Additionally, recent data suggest that neutrophils could be considered one of the emerging targets for multiple cancer types. This review summarizes the most recent updates regarding neutrophil recruitments and functions in the tumor microenvironment as well as potential development of neutrophils-targeted putative therapeutic strategies.
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Lin J, Zhang W, Huang Y, Chen W, Wu R, Chen X, Lou N, Wang P. Sarcopenia is associated with the neutrophil/lymphocyte and platelet/lymphocyte ratios in operable gastric cancer patients: a prospective study. Cancer Manag Res 2018; 10:4935-4944. [PMID: 30464594 PMCID: PMC6208548 DOI: 10.2147/cmar.s175421] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Purpose Sarcopenia is distinguished by decreased skeletal muscle plus low muscle strength and/or physical performance. This study was designed to demonstrate the relationship between sarcopenia and systemic inflammatory response (neutrophil/lymphocyte ratio [NLR], platelet/lymphocyte ratio [PLR], and large platelet/lymphocyte ratio [LPLR]) prior to radical gastrectomy for gastric cancer. Patients and methods We conducted a prospective study of gastric cancer patients who underwent radical gastrectomy. The clinical utility of the NLR, PLR, and LPLR was evaluated by receiver operating characteristic curves. Sarcopenia components including skeletal muscle index, handgrip strength, and 6 m usual gait speed were measured. Logistic analysis was used to identify the independent indices associated with sarcopenia. Results A total of 670 patients were included, representing 504 men and 166 women. Of these, 104 patients (15.5%) were diagnosed with sarcopenia and 567 (84.5%) were non-sarcopenia. PLR has a diagnostic sensitivity of 91.3% for sarcopenia. In addition to the indicators of preoperative age, nutritional risk screening, body mass index, preoperative albumin, and diabetes, the NLR and PLR were independent predictors for sarcopenia (P<0.05). Conclusion The present study showed that at-diagnosis sarcopenia was associated with inflammation in patients with operable gastric cancer. Due to the complex assessment of muscle condition, PLR may be used as a primary screening test for sarcopenia. How systemic inflammatory response influences changes in sarcopenia may provide new therapeutic perception toward improving outcomes.
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Affiliation(s)
- Ji Lin
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China,
| | - Weiteng Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China,
| | - Yunshi Huang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China,
| | - Weisheng Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China,
| | - Ruisen Wu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China,
| | - Xiaodong Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China,
| | - Neng Lou
- Department of General Surgery, Zhejiang University Huzhou Hospital, Huzhou, Zhejiang, China,
| | - Pengfei Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China,
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Ogata T, Satake H, Ogata M, Hatachi Y, Inoue K, Hamada M, Yasui H. Neutrophil-to-lymphocyte ratio as a predictive or prognostic factor for gastric cancer treated with nivolumab: a multicenter retrospective study. Oncotarget 2018; 9:34520-34527. [PMID: 30349646 PMCID: PMC6195378 DOI: 10.18632/oncotarget.26145] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Accepted: 09/08/2018] [Indexed: 02/07/2023] Open
Abstract
Introduction The neutrophil-to-lymphocyte ratio (NLR) is effective as a predictive factor for lung cancer treated with nivolumab. The objective of this study was to determine the effectiveness of NLR for patients with advanced gastric cancer (AGC) treated with nivolumab. Methods This was a multicenter, retrospective study of patients with AGC treated with nivolumab from June 2017 to December 2017. The NLRs were calculated before the first cycle (NLRpre) and two weeks after the first administration (NLRpost). Results Twenty-six patients were enrolled (males 19, females 7) with a median age of 64 years. The overall response rate was 15%. The median PFS was 80 days (range, 11 – 265) and the median OS was 290 days (range, 21 – 332). Stratified with high NLR (≥5) and low NLR (<5), the median PFS was shorter in the high NLRpre arm (87 vs. 45 days; p=0.066) and significantly shorter in the high NLRpost arm (94 vs. 28 days; p=0.014). The median OS was significantly shorter in the high NLRpre arm (290 vs. 175 days; p=0.008) and in the high NLRpost arm (290 vs. 69 days; p<0.001). Conclusion NLR may be an effective prognostic factor in patients with AGC treated with nivolumab.
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Affiliation(s)
- Takatsugu Ogata
- Department of Medical Oncology, Kobe City Medical Center General Hospital, Chuo-ku, Kobe City, Hyogo, 650-0047, Japan
| | - Hironaga Satake
- Cancer Treatment Center, Kansai Medical University Hospital, Shinmachi, Hirakata City, Osaka, 573-1191, Japan
| | - Misato Ogata
- Department of Medical Oncology, Kobe City Medical Center General Hospital, Chuo-ku, Kobe City, Hyogo, 650-0047, Japan
| | - Yukimasa Hatachi
- Department of Medical Oncology, Kobe City Medical Center General Hospital, Chuo-ku, Kobe City, Hyogo, 650-0047, Japan
| | - Kentaro Inoue
- Department of Surgery, Kansai Medical University Hospital, Shinmachi, Hirakata City, Osaka, 573-1191, Japan
| | - Madoka Hamada
- Department of Surgery, Kansai Medical University Hospital, Shinmachi, Hirakata City, Osaka, 573-1191, Japan
| | - Hisateru Yasui
- Department of Medical Oncology, Kobe City Medical Center General Hospital, Chuo-ku, Kobe City, Hyogo, 650-0047, Japan
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Lazăr DC, Avram MF, Romoșan I, Cornianu M, Tăban S, Goldiș A. Prognostic significance of tumor immune microenvironment and immunotherapy: Novel insights and future perspectives in gastric cancer. World J Gastroenterol 2018; 24:3583-3616. [PMID: 30166856 PMCID: PMC6113718 DOI: 10.3748/wjg.v24.i32.3583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2018] [Revised: 06/05/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
Despite a decrease in gastric cancer incidence, the development of novel biologic agents and combined therapeutic strategies, the prognosis of gastric cancer remains poor. Recently, the introduction of modern immunotherapy, especially using immune checkpoint inhibitors, led to an improved prognosis in many cancers. The use of immunotherapy was also associated with manageable adverse event profiles and promising results in the treatment of patients with gastric cancer, especially in heavily pretreated patients. These data have led to an accelerated approval of some checkpoint inhibitors in this setting. Understanding the complex relationship between the host immune microenvironment and tumor and the immune escape phenomenon leading to cancer occurrence and progression will subsequently lead to the identification of prognostic immune markers. Furthermore, this understanding will result in the discovery of both new mechanisms for blocking tumor immunosuppressive signals and pathways to stimulate the local immune response by targeting and modulating different subsets of immune cells. Due to the molecular heterogeneity of gastric cancers associated with different clinico-biologic parameters, immune markers expression and prognosis, novel immunotherapy algorithms should be personalized and addressed to selected subsets of gastric tumors, which have been proven to elicit the best clinical responses. Future perspectives in the treatment of gastric cancer include tailored dual immunotherapies or a combination of immunotherapy with other targeted agents with synergistic antitumor effects.
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Affiliation(s)
- Daniela Cornelia Lazăr
- Department of Internal Medicine I, University Medical Clinic, University of Medicine and Pharmacy “Victor Babeş”, Timişoara 300041, Timiş County, Romania
| | - Mihaela Flavia Avram
- Department of Surgery X, 1st Surgery Clinic, University of Medicine and Pharmacy “Victor Babeş”, Timişoara 300041, Timiş County, Romania
| | - Ioan Romoșan
- Department of Internal Medicine I, University Medical Clinic, University of Medicine and Pharmacy “Victor Babeş”, Timişoara 300041, Timiş County, Romania
| | - Mărioara Cornianu
- Department of Pathology, University of Medicine and Pharmacy “Victor Babeş”, Timişoara 300041, Timiş County, Romania
| | - Sorina Tăban
- Department of Pathology, University of Medicine and Pharmacy “Victor Babeş”, Timişoara 300041, Timiş County, Romania
| | - Adrian Goldiș
- Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy “Victor Babeş”, Timişoara 300041, Timiş County, Romania
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