Tumor-infiltrating Neutrophils is Prognostic and Predictive for Postoperative Adjuvant Chemotherapy Benefit in Patients With Gastric Cancer

Zhang, Heng; Líu, Hao; Shen, Zhongliang; Lin, Chao; Wang, Xuefei; Qin, Jing; Qin, Xinyu; Xu, Jiejie; Sun, Yihong

doi:10.1097/sla.0000000000002058

Cited by 181 publications

(171 citation statements)

References 51 publications

Supporting

Mentioning

163

Contrasting

Order By: Relevance

“…whereas IFN-b can regulate the antitumor phenotype of N1. 9,28,42 In our study, low TIN predict a favorable survival for biliary cancer.…”

Section: Discussionsupporting

confidence: 53%

“…TIN can be attracted by granulocyte colony‐stimulating factor (G‐CSF), granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), chemokine (C‐X‐C motif) ligand (CXCL)1, CXCL2, CXCL5 and CXCL8 secreted by cancer cells, endothelial cells or fibroblasts . Simultaneously, G‐CSF and transforming growth factor beta (TGF‐β) can control the immunosuppressive function of N2 by regulating transcription factors inhibitor of DNA binding 1 (ID1), retinoblastoma 1 (RB1) and interferon regulatory factor 8 (IRF8), whereas IFN‐β can regulate the antitumor phenotype of N1 . In our study, low TIN predict a favorable survival for biliary cancer.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Tumor‐infiltrating neutrophils predict prognosis and adjuvant chemotherapeutic benefit in patients with biliary cancer

Wang

Suo

et al. 2018

Cancer Science

Self Cite

View full text Add to dashboard Cite

Tumor‐infiltrating neutrophils (TIN) carry out quite significant but opposite functions in different cancers, and their function in biliary cancer has not been fully characterized. To investigate the prognostic significance of TIN in biliary cancer, a training set (n = 118) and a validation set (n = 127) were involved in this study. TIN were evaluated by immunohistochemical staining of CD66b, and then defined as low (neutrophils <18/high‐power field [HPF]) vs high (neutrophils ≥18/HPF). Kaplan‐Meier curve, Cox proportional hazards models and receiver operating characteristic curve were used to assess the prognostic significance. TIN was identified as an independent prognostic factor for overall survival in the training set (HR: 4.720; 95% CI: 2.623‐8.493; P < .001) which was confirmed in the validation set (HR: 4.993; 95% CI: 2.626‐9.492; P < .001). Notably, among patients with stage III and IV disease, those with low TIN could benefit from adjuvant chemotherapy, with a reduced risk of compromised survival compared with those with high TIN (HR: 0.294; 95% CI: 0.099‐0.873; P = .047 in the training set; and HR: 0.100; 95% CI: 0.022‐0.462; P = .006 in the validation set). In addition, TIN were negatively related to biological pathways as regulation of activated T‐cell proliferation and lymphocyte‐mediated immunity, and showed a negative correlation with CD8 + T cells (r = −.324, P < .001). Taken together, our results implicate TIN as an independent marker of prognosis and indicator of patients who would benefit from adjuvant chemotherapy in biliary cancer.

show abstract

“…whereas IFN-b can regulate the antitumor phenotype of N1. 9,28,42 In our study, low TIN predict a favorable survival for biliary cancer.…”

Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Tumor‐infiltrating neutrophils predict prognosis and adjuvant chemotherapeutic benefit in patients with biliary cancer

Wang

Suo

et al. 2018

Cancer Science

Self Cite

View full text Add to dashboard Cite

show abstract

“…Li et al19 showed that TANs are an independent and unfavorable factor in the prognosis of gastric cancer patients. However, Sun et al26 found that gastric cancer patients with high CD66b + TAN levels gain a survival benefit and are prone to improved OS from postoperative adjuvant chemotherapy. In contrast, low TAN levels identified a subgroup of muscle invasive bladder cancer (MIBC) patients who appeared to benefit from adjuvant chemotherapy 16.…”

Section: Discussionmentioning

confidence: 99%

“…However, other studies have revealed that tumor‐infiltrating neutrophils are associated with a better prognosis in CRC and might promote antitumor immunity 22, 25. CD66b was found to be a reliable marker to identify TANs in cancer tissues using immunohistochemistry, including in CRC tissues 17, 19, 22, 24, 26. Thus, the prognostic role of TANs in CRC is not yet conclusive, and the relationship of IL‐37 and CD66b + TANs has not been previously elucidated.…”

Section: Introductionmentioning

confidence: 96%

Prognostic significance of nomograms integrating IL‐37 expression, neutrophil level, and MMR status in patients with colorectal cancer

et al. 2018

View full text Add to dashboard Cite

Interleukin (IL)‐37 and neutrophils are considered to be involved in human cancer, but their prognostic significance in colorectal cancer (CRC) has not been elucidated. The aim of this study was to evaluate the prognostic value of IL‐37 expression and neutrophil levels in CRC. We retrospectively analyzed IL‐37 expression, CD66b+ neutrophil levels, and mismatch repair (MMR) status in 337 paraffin‐embedded CRC specimens from the training cohort by immunohistochemistry. Their prognostic values were assessed using Kaplan‐Meier curves and multivariate Cox regression models. Moreover, several risk factors were used to form nomograms to evaluate survival, and the performance of the nomograms was assessed with respect to calibration, discrimination, and clinical usefulness. Further validation was performed in an independent cohort of 245 cases. Low IL‐37 expression and high CD66b+ neutrophil levels were significantly associated with diminished disease‐free survival (DFS) and overall survival (OS), and patients with MMR‐deficient CRC had better clinical outcomes. Furthermore, multivariate Cox analysis identified IL‐37, CD66b+ neutrophils, and MMR status as independent prognostic factors for DFS and OS. Two nomograms integrating the three markers with four clinicopathological risk factors were developed and validated for predicting DFS and OS with good calibration and discrimination (C‐index: training cohort, 0.798 (95% confidence interval:0.764‐0.832) and 0.828 (0.796‐0.860), respectively; validation cohort, 0.739 (0.696‐0.783) and 0.761 (0.715‐0.808), respectively). Decision curve analysis demonstrated that the nomograms were clinically useful. Intratumoral IL‐37, CD66b+ neutrophils, and MMR status were independent prognostic factors for CRC patients. Nomograms incorporating these biomarkers and clinicopathological features could be conveniently used to facilitate the individualized prediction of DFS and OS.

show abstract

“…Formalin-fixed paraffin-embedded surgical specimens were used for tissue microarray (TMA) construction and subsequent immunohistochemistry study as described previously. 20 The TMA slide was dried 2 hr at 608C, the sections were dewaxed in xylene and graded alcohols, hydrated and washed in phosphate-buffered saline. After the endogenous peroxidase was inhibited by 3% H 2 O 2 for 30 min, the sections were pretreated in a microwave oven (15 min in sodium citrate buffer, pH 6) and then incubated with 10% normal goat serum for 60 min.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Low tumor infiltrating mast cell density confers prognostic benefit and reflects immunoactivation in colorectal cancer

Mao

Feng

Zheng

et al. 2018

Intl Journal of Cancer

View full text Add to dashboard Cite

The role of mast cells (MCs) in colorectal cancer (CRC) progression was controversial. Thus, our study was designed to evaluate the prognostic value of MCs as well as their correlation with immune microenvironment. A retrospective cohort of CRC patients of stages I-IV was enrolled in our study. Consecutive patients (854) were divided into training set (427 patients) and validation set (427 patients) randomly. The findings were further validated in a GEO cohort, GSE39582 (556 patients). The mast cell density (MCD) was measured by immunohistochemical staining of tryptase or by CIBERSORT algorithm. Low MCD predicted prolonged overall survival (OS) in training and validation set. Moreover, MCD was identified as an independent prognostic indicator in both sets. Better stratification for CRC prognosis can be achieved by building a MCD based nomogram. The prognostic role of MCD was further validated in GSE39582. In addition, MCD predicted improved survival in stages II and III CRC patients receiving adjuvant chemotherapy (ACT). Multiple immune pathways were enriched in low MCD group while cytokines/chemokines promoting anti-tumor immunity were highly expressed in such group. Furthermore, MCD was negatively correlated with CD8+ T cells infiltration. In conclusion, MCD was identified as an independent prognostic factor, as well as a potential biomarker for ACT benefit in stages II and III CRC. Better stratification of CRC prognosis could be achieved by building a MCD based nomogram. Moreover, immunoactivation in low MCD tumors may contributed to improved prognosis.

show abstract

Tumor-infiltrating Neutrophils is Prognostic and Predictive for Postoperative Adjuvant Chemotherapy Benefit in Patients With Gastric Cancer

Abstract: TIN in gastric cancer was identified as an independent prognostic factor, which could be incorporated into standard TNM staging system to refine risk stratification and predict for overall survival benefit from postoperative chemotherapy in patients with gastric cancer.

Cited by 181 publications

References 51 publications

Tumor‐infiltrating neutrophils predict prognosis and adjuvant chemotherapeutic benefit in patients with biliary cancer

Tumor‐infiltrating neutrophils predict prognosis and adjuvant chemotherapeutic benefit in patients with biliary cancer

Prognostic significance of nomograms integrating IL‐37 expression, neutrophil level, and MMR status in patients with colorectal cancer

Low tumor infiltrating mast cell density confers prognostic benefit and reflects immunoactivation in colorectal cancer

Contact Info

Product

Resources

About