Prognostic Biomarkers for Gastric Cancer: An Umbrella Review of the Evidence

Zhou, Cen; Zhong, Xi; Song, Yongxi; Shi, Jinxin; Wu, Zhonghua; Guo, Zhexu; Sun, Jie; Wang, Zhenning

doi:10.3389/fonc.2019.01321

Cited by 12 publications

(7 citation statements)

References 106 publications

(35 reference statements)

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“…Although many prognostic signatures have been developed for GC, reliable biomarkers based on the intrinsic biological characteristics within the TME are yet to be developed (Zhou et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

A novel adenosine signalling‐based prognostic signature in gastric cancer and its association with cancer immune features and immunotherapy response

Wang

et al. 2023

Cell Biology International

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Reliable prognostic signatures that can reflect the intrinsic characteristics of gastric cancer (GC) are still rare. Here, we developed an adenosine‐based prognostic signature and explored its association with the tumour immune in GC patients, aiming at confirming the prognostic value of adenosine‐related genes and guiding the GC risk stratification and immunotherapeutic response prediction. We collected adenosine pathway‐related genes from STRING websites and manual searching. We enrolled the The Cancer Genome Atlas cohort and four gene expression omnibus cohorts of GC for generating and validating the adenosine pathway‐based signature using the Cox regression method. Gene expression in the signature was verified using polymerase chain reaction. We also performed gene set enrichment analysis, immune infiltration assessment and immunotherapy response prediction based on this signature. Our study resulted in a six‐gene adenosine signature (GNAS, CXCR4, PPP1R1B, ADCY6, NT5E and NOS3) for risk stratification of GC prognosis, with the highest area under the receiver operating characteristic curve up to 0.767 for predicting 10‐year overall survival (OS). In the training cohort, patients with signature‐defined high risk had significantly poorer OS than those with low risk (p < .001). Multivariate analysis identified the signature as an independent prognostic factor (hazard ratio 2.863, 95% confidence interval [1.871–4.381], p < .001). These findings were confirmed in four independent cohorts. Expression detection showed that all signature genes were upregulated in both GC tissues and cell lines. Further analysis revealed that the signature‐defined high‐risk patients were characterised by immunosuppressive states and associated with a poor immunotherapy response. In conclusion, the adenosine pathway‐based signature represents a promising risk stratification tool for GC in guiding individualised prognostication and immunotherapy.

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Section: Discussionmentioning

confidence: 99%

A novel adenosine signalling‐based prognostic signature in gastric cancer and its association with cancer immune features and immunotherapy response

Wang

et al. 2023

Cell Biology International

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“…Systematic inflammation is closely related to cancer development, and inflammation may already exist at early stages of tumorigenesis ( 19 ). Cancer cells produce granulocyte colony-stimulating factor (G-CSF), which promotes the upregulation of circulating neutrophils ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

Preoperative peripheral blood inflammatory markers especially the fibrinogen-to-lymphocyte ratio and novel FLR-N score predict the prognosis of patients with early-stage resectable extrahepatic cholangiocarcinoma

Zhang

Lou

et al. 2022

Front. Oncol.

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BackgroundSystemic inflammation is important in the development of extrahepatic cholangiocarcinoma (ECC). The aim of this study was to compare the prognostic power of preoperative peripheral blood inflammatory markers and the novel FLR-N score in patients with resectable ECC.MethodsA total of 140 patients with resectable ECC and 140 healthy controls (HCs) were recruited for the study. The Mann−Whitney U test was used to evaluate the differences in inflammatory markers between groups. Kaplan−Meier and Cox regression analyses were used to evaluate the prognostic power of preoperative fibrinogen, albumin, prealbumin, bilirubin, neutrophils, lymphocytes, monocytes, platelets, fibrinogen-to-lymphocyte ratio (FLR), fibrinogen-to-albumin ratio (FAR), fibrinogen-to-prealbumin ratio (FPR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), FLR-neutrophil (FLR-N) score, and CA19-9 in patients with resectable ECC. Nomogram was developed based on the results of multivariate Cox analyses.ResultsPatients with resectable ECC had significantly higher levels of neutrophils, monocytes, fibrinogen, FLR, FAR, FPR, NLR, PLR, and MLR and lower levels of lymphocytes, albumin, and prealbumin than HCs (all P < 0.01). Albumin, prealbumin, and FPR had a good ability to distinguish between ECC patients with total bilirubin < 34 µmol/L and HCs (AUCs of 0.820, 0.827, and 0.836, respectively). Kaplan−Meier analysis showed that high neutrophil, fibrinogen, FLR, FAR, PLR, MLR, and FLR-N score values were associated with poor survival in patients with resectable ECC. Multivariate analyses indicated that neutrophils (P = 0.022), FLR (P = 0.040), FLR-N score (P < 0.0001), and positive lymph node metastasis (P = 0.016) were independent factors for overall survival (OS). Nomogram were developed to predict OS for patients with ECC.ConclusionThe prognostic roles of inflammatory markers in patients with resectable ECC were different. The preoperative neutrophil count, FLR and FLR-N score could serve as noninvasive markers for predicting the prognosis of resectable ECC.

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“…Molecular subtyping of GC involves the screening of the genes or protein markers related to tumorigenesis, diagnosis, and prognosis. The currently studied genes and protein markers include oncogenes, tumor suppressor genes, intercellular adhesion molecules, growth factors, and certain hormone receptors[ 17 ]. Although most of them show poor sensitivity, specificity, or reliability, a few have been recognized as effective biomarkers.…”

Section: Discussionmentioning

confidence: 99%

Cost-effective low-coverage whole-genome sequencing assay for the risk stratification of gastric cancer

Ye¹,

Mao²,

Zhou³

et al. 2022

WJGO

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BACKGROUND Gastric cancer (GC), a multifactorial disease, is caused by pathogens, such as Helicobacter pylori ( H. pylori ) and Epstein-Barr virus (EBV), and genetic components. AIM To investigate microbiomes and host genome instability by cost-effective, low-coverage whole-genome sequencing, as biomarkers for GC subtyping. METHODS Samples from 40 GC patients were collected from Taizhou Hospital, Zhejiang Province, affiliated with Wenzhou Medical University. DNA from the samples was subjected to low-coverage whole-genome sequencing with a median genome coverage of 1.86 × (range: 1.03 × to 3.17 ×) by Illumina × 10, followed by copy number analyses using a customized bioinformatics workflow ultrasensitive chromosomal aneuploidy detector. RESULTS Of the 40 GC samples, 20 (50%) were found to be enriched with microbiomes. EBV DNA was detected in 5 GC patients (12.5%). H. pylori DNA was found in 15 (37.5%) patients. The other 20 (50%) patients were found to have relatively higher genomic instability. Copy number amplifications of the oncogenes, ERBB2 and KRAS, were found in 9 (22.5%) and 7 (17.5%) of the GC samples, respectively. EBV enrichment was found to be associated with tumors in the gastric cardia and fundus. H. pylori enrichment was found to be associated with tumors in the pylorus and antrum. Tumors with elevated genomic instability showed no localization and could be observed in any location. Additionally, H. pylori- enriched GC was found to be associated with the Borrmann type II/III and gastritis history. EBV-enriched GC was not associated with gastritis. No statistically significant correlation was observed between genomic instability and gastritis. Furthermore, these three different molecular subtypes showed distinct survival outcomes ( P = 0.019). EBV-positive tumors had the best prognosis, whereas patients with high genomic instability (CIN+) showed the worst survival. Patients with H. pylori infection showed intermediate prognosis compared with the other two subtypes. CONCLUSION Thus, using low-coverage whole-genome sequencing, GC can be classified into three categories based on disease etiology; this classification may prove useful for GC diagnosis and precision medicine.

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Prognostic Biomarkers for Gastric Cancer: An Umbrella Review of the Evidence

Cited by 12 publications

References 106 publications

A novel adenosine signalling‐based prognostic signature in gastric cancer and its association with cancer immune features and immunotherapy response

A novel adenosine signalling‐based prognostic signature in gastric cancer and its association with cancer immune features and immunotherapy response

Preoperative peripheral blood inflammatory markers especially the fibrinogen-to-lymphocyte ratio and novel FLR-N score predict the prognosis of patients with early-stage resectable extrahepatic cholangiocarcinoma

Cost-effective low-coverage whole-genome sequencing assay for the risk stratification of gastric cancer

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