Neutrophil-Lymphocyte Ratio and Circulating Tumor Cells Counts Predict Prognosis in Gastrointestinal Cancer Patients

Qian, Chao; Cai, Renjie; Zhang, Wenying; Wang, Jiong-Yi; Hu, Xiaohua; Zhang, Yanjie; Jiang, Bin; Han, Yuanfei; Liu, Feng

doi:10.3389/fonc.2021.710704

Cited by 20 publications

(12 citation statements)

References 41 publications

(71 reference statements)

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“…Meanwhile, all 3 genes were negatively related to the infiltration of CD4+ T and dendritic cells and positively related to the infiltration of neutrophils. Previous studies also identified that higher infiltration of neutrophils was consistent with poor survival status in numerous types of cancer [ 33 – 35 ]. Moreover, the expression of MAFF was negatively associated with the infiltration of CD8+ T cells.…”

Section: Resultsmentioning

confidence: 73%

Distinct Hypoxia-Related Gene Profiling Characterizes Clinicopathological Features and Immune Status of Mismatch Repair-Deficient Colon Cancer

Cao

et al. 2021

Journal of Oncology

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Despite dramatic responses to immune checkpoint inhibitors (ICIs) in patients with colon cancer (CC) harboring deficient mismatch repair (dMMR), more than half of these patients ultimately progress and experience primary or secondary drug resistance. There is no useful biomarker that is currently validated to accurately predict this resistance or stratify patients who may benefit from ICI-based immunotherapy. As hypoxic and acidic tumor microenvironment would greatly impair tumor-suppressing functions of tumor-infiltrating lymphocytes (TILs), we sought to explore distinct immunological phenotypes by analysis of the intratumoral hypoxia state using a well-established gene signature. Based on the Gene Expression Omnibus (GEO) (n = 88) and The Cancer Genome Atlas (TCGA) (n = 49) databases of patients with CC, we found that dMMR CC patients could be separated into normoxia subgroup (NS) and hypoxia subgroup (HS) with different levels of expression of hypoxia-related genes (lower in NS group and higher in HS group) using NMF package. Tumoral parenchyma in the HS group had a relatively lower level of immune cell infiltration, particularly CD8+ T cells and M1 macrophages than the NS group, and coincided with higher expression of immune checkpoint molecules and C-X-C motif chemokines, which might be associated with ICI resistance and prognosis. Furthermore, three genes, namely, MT1E, MT2A, and MAFF, were identified to be differentially expressed between NS and HS groups in both GEO and TCGA cohorts. Based on these genes, a prognostic model with stable and valuable predicting ability has been built for clinical application. In conclusion, the varying tumor-immune microenvironment (TIME) classified by hypoxia-related genes might be closely associated with different therapeutic responses of ICIs and prognosis of dMMR CC patients.

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Section: Resultsmentioning

confidence: 73%

Distinct Hypoxia-Related Gene Profiling Characterizes Clinicopathological Features and Immune Status of Mismatch Repair-Deficient Colon Cancer

Cao

et al. 2021

Journal of Oncology

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“…A total of 14 retrospective cohort studies were included ( 22 – 35 ), including 1053 patients. These studies were published from 2007 to 2021 (3 articles ( 23 , 29 , 35 ) were published in 2021). Six studies ( 23 , 25 , 26 , 32 , 34 , 35 ) were conducted in China; others were carried out in Poland ( 22 ), Brazil ( 24 ), Germany ( 28 ), South Korea ( 29 ), Japan ( 27 , 30 , 31 , 33 ) and other countries.…”

Section: Resultsmentioning

confidence: 99%

“…These studies were published from 2007 to 2021 (3 articles ( 23 , 29 , 35 ) were published in 2021). Six studies ( 23 , 25 , 26 , 32 , 34 , 35 ) were conducted in China; others were carried out in Poland ( 22 ), Brazil ( 24 ), Germany ( 28 ), South Korea ( 29 ), Japan ( 27 , 30 , 31 , 33 ) and other countries. Ten studies ( 22 , 23 , 26 , 27 , 29 , 30 , 32 – 35 ) reported the relationship between CTC and OS in gastric cancer patients, 3 ( 25 , 28 , 31 ) reported the relationship between CTC and OS or PFS in patients with gastric cancer, and 1 study ( 24 ) reported the relationship between CTC and PFS in patients with gastric cancer.…”

Section: Resultsmentioning

confidence: 99%

The prognostic role of circulating tumor cells in gastric cancer: A meta-analysis

Song

Han

et al. 2022

Front. Oncol.

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ObjectiveWe conducted a meta-analysis to evaluate the relationship between circulating tumor cells (CTC) and the prognosis of patients with gastric cancer.Materials and methodsThe cohort studies reporting on the relationship between CTC and prognosis of gastric cancer were collected from Pubmed, Cochrane, Embase, CNKI, WanFang Data, and VIP databases. The two researchers independently screened the literature, extracted the data, and evaluated the bias risk of the included literature. The data were analyzed by Revman software (Review Manager version 5.4).ResultA total of 14 retrospective cohort studies with 1053 patients were included. The results showed that the overall survival time (OS) and progression-free survival time (PFS) of CTC-positive patients were shorter compared to CTC-negative patients. Taking into consideration the critical value of CTC positive patients, country of origin, sample size, treatment mode, and study time, the subgroup analysis showed that CTC-positive was related to the shortening of OS in patients with gastric cancer. Based on the subgroup analysis of the factors such as CTC positive critical value < 2.8, sample size ≥ 75, mixed therapy, longer study duration, country, and immunofluorescence detection of CTC, it was found that OS in CTC positive group was shorter than that in CTC-negative group (all P<0.05), while the critical value of positive CTC ≥ 2.8, sample size ≥ 75, choice of treatment only for operation or non-operation, short study time and molecular detection of CTC were not associated with OS (all P>0.05). In addition, CTC-positive patients had a more advanced TNM staging, poorer tumor differentiation, and earlier distant metastasis.ConclusionCTC can be used as a prognostic indicator of gastric cancer. Gastric cancer patients with positive CTC may have a poorer prognosis compared to those with CTC-negative tumors.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022323155.

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“…The reason why we decided to analyze the internal relationships within phenotypically determined related populations is that the mentioned NLR or LMR are calculated based on the results of automated blood counters that cannot recognize subtle differences between individual cells within a related population. For example, it is generally accepted that high NLR and/or low LMR in tumor patients, including CRC patients, are associated with poor outcome [47][48] . However, it is also known that the composition of circulating neutrophils in tumor patients is diverse and includes high-density neutrophils (HDN), which are thought to have anti-tumor properties and correspond to N1 neutrophils in TME, as well as low-density neutrophils (LDN) with pro-tumor effects, which correspond to N2 49 .…”

Section: Discussionmentioning

confidence: 99%

Myeloid-derived suppressor-like cells - a potential biomarker for prognosis of colorectal cancer?

et al. 2023

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Background/Aim. Myeloid-derived suppressor cells (MDSC) represent a heterogeneous group of immature cells of myeloid origin, which have the ability to inhibit both the innate and adaptive immune response. Due to its immunosuppressive effect, MDSC can promote the growth and progression of cancer. Colorectal cancer (CRC) is one of the most common cancers in the general population for whose advanced stages of the disease there is still no good therapy. In addition to contributing to the development and spread of CRC, MDSC could potentially be markers of its prognosis. The aim of the study was to examine the potential prognostic role of peripheral blood MDSC counts in CRC patients. Methods. In a prospective study we analyzed the possibility of using CD16low granulocytes and mononuclear (M-MDSC) like cells as well as neutrophyl to lymphocyte ratio (NLR), lymphocite to monocyte ratio (LMR), CD16hi/CD16low granulocytes ratio and M/MMDSC like cells ratios before starting of the treatment as a biomarker for overall survival (OS) in patients with CRC. Hazards ratios (HRs) with the corresponding 95% confidence intervals (95%CIs) were calculated to evaluate the prognostic role of MDSCs in cancer. Results. The analysis was performed in 47 patients in stage III and IV CRC according to the TNM/AJCC disease classification. Dependable data were obtained in 32 patients. Patients blood samples are taken before the possible start of treatment (surgery, chemotherapy). Increased percentage and absolute values of CD16low granulocytes as well as absolute values of M-MDSC-like cells have been shown to be associated with shorter overall survival (OS) (p < 0.0066, p < 0.0013 and p < 0.0119, respectively). The relationship of CD16hi/CD16low granulocytes ratio and M/M-MDSC like cells ratio with OS indicated the existence of positive correlations between these parameters, which higher value of this relationship indicated longer survival of patients (p < 0.0054 and p < 0.0426, respectively). Relationship between OS and NLR indicators found statistically significant inverse correlation with NLR (p = 0.0349). No statistical significance was found in the relationship between OS and LMR. Conclusion. This study shows that percent and absolute numbers of CD16low granulocytes, as well as absolute number of M-MDSC like cells, CD16hi/CD16low granulocytes ratio, M/M-MDSC like cells and NLR ratio ratio may be reliable indicators of survival in patients with CRC.

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Neutrophil-Lymphocyte Ratio and Circulating Tumor Cells Counts Predict Prognosis in Gastrointestinal Cancer Patients

Cited by 20 publications

References 41 publications

Distinct Hypoxia-Related Gene Profiling Characterizes Clinicopathological Features and Immune Status of Mismatch Repair-Deficient Colon Cancer

Distinct Hypoxia-Related Gene Profiling Characterizes Clinicopathological Features and Immune Status of Mismatch Repair-Deficient Colon Cancer

The prognostic role of circulating tumor cells in gastric cancer: A meta-analysis

Myeloid-derived suppressor-like cells - a potential biomarker for prognosis of colorectal cancer?

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