Gastric cancer (GC) is one of the most common malignant tumors globally. Guiding the individualized treatment of GC is the focus of research. Obtaining representative biological samples to study the biological characteristics of GC is the focus of diagnosis and treatment of GC. Liquid biopsy technology can use high-throughput sequencing technology to detect biological genetic information in blood. Compared with traditional tissue biopsy, liquid biopsy can determine the dynamic changes of tumor. As a noninvasive auxiliary diagnostic method, liquid biopsy can provide diagnostic and prognostic information concerning the progression of the disease. Liquid biopsy includes circulating tumor cells, circulating tumor DNA, circulating tumor RNA, tumor educated platelets, exosomes, and cytokines. This article describes the classification of liquid biopsy and its application value in the occurrence, development, and therapeutic efficacy of GC.

• CXCR4
• VEGF
• angiogenesis
• gastric cancer
• lymph node metastases
• lymphangiogenesis

• CXCR4
• gastric cancer
• gastric precancerous lesions
• immune infiltrates
• malignant transformation

• CC chemokine subfamily
• cancer
• chemoresistance
• inflammation
• platinum drugs

• Cell Proliferation
• Chemokines, CC/classification
• Chemokines, CC/immunology
• Drug Resistance, Neoplasm/immunology
• Humans
• Inflammation/genetics
• Neoplasms/drug therapy
• Neoplasms/immunology
• Platinum/therapeutic use
• Signal Transduction/drug effects
• Tumor Microenvironment/drug effects
• Tumor Microenvironment/immunology

• HOTAIR
• CXCR4
• RhoA
• gastric cancer
• metastasis
• miR-126

• 3' Untranslated Regions
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs/genetics
• Neoplasm Metastasis
• RNA, Long Noncoding/genetics
• Receptors, CXCR4/genetics
• Signal Transduction
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• rhoA GTP-Binding Protein/metabolism

• 2017-ZQN-18 Young and middle-aged key personnel training program for provincial health planning students
• 2014-2-8 Provincial Youth Health Science Research Project
• 2017-1-13 Provincial Youth Health Science Research Project
• 2016J01436 Natural Science Foundation of Fujian
• 2013-2016 National key clinical specialty construction project

• CXCR4
• biomarker
• gastrointestinal cancer
• hazard ratio
• prognosis

To determine whether p21-activated Kinase (PAK) 6 is a prognostic and predictive marker in gastric cancer (GC) and to construct a classifier that can identify a subset of patients who are highly sensitive to 5-fluorouracil/oxaliplatin chemotherapy. We retrospectively analyzed the expression levels of PAK6, cyclooxygenase 2, p21^WAF1, Ki-67, excision repair cross-complementing gene 1, and thymidylate synthase in 242 paraffin-embedded GC specimens of the training cohort by immunohistochemistry. Then, we used support vector machine (SVM)–based methods to develop a predictive classifier for chemotherapy (chemotherapy score – CS-SVM classifier). Further validation was performed in an independent cohort of 279 patients. High PAK6 expression was associated with poor prognosis and increased chemoresistance to 5-FU/oxaliplatin chemotherapy. The CS-SVM classifier distinguished patients with stage II and III GC into low- and high-CS-SVM groups, with significant differences in the 5-year disease-free survival (DFS) and overall survival (OS) in chemotherapy patients. Moreover, chemotherapy significantly prolonged the DFS and OS of the high CS-SVM patients in the training and validation cohorts. In conclusion, PAK6 was an independent prognostic factor and increased chemoresistance. The CS-SVM classifier distinguished a subgroup of stage II and III patients who would highly benefit from chemotherapy, thus facilitating patient counseling and individualizing the management.

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p21-activated Kinase 6 was a predictive biomarker and increased chemoresistance to 5-FU/oxaliplatin chemotherapy.

PAK6 was an independent prognostic factor and increased chemoresistance. The chemotherapy score – support vector machine classifier distinguished a subgroup of stage II and III patients who would highly benefit from chemotherapy. The model maybe useful for patient counseling and individualized treatment decision-making.

• 5-FU/oxaliplatin chemotherapy
• Gastric cancer
• Nomogram
• SVM classifier
• p21-activated kinase 6

• CXCL12
• CXCR4
• CXCR7
• gastric carcinoma
• inhibitor
• targeted therapy

• Animals
• Chemokine CXCL12/antagonists & inhibitors
• Chemokine CXCL12/metabolism
• Humans
• Molecular Targeted Therapy
• Receptors, CXCR4/antagonists & inhibitors
• Receptors, CXCR4/metabolism
• Signal Transduction
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/pathology

• CXC chemokine receptor-7
• Gastric cancer
• Liver metastasis
• Lymph node metastasis
• Stromal cell derived factor-1

• Aged
• Carcinoma/pathology
• Carcinoma/secondary
• Cell Line, Tumor
• Cell Proliferation
• Chemokine CXCL12/metabolism
• Female
• Gene Knockdown Techniques
• Humans
• Immunohistochemistry
• Liver/pathology
• Liver Neoplasms/pathology
• Liver Neoplasms/secondary
• Lymph Nodes/pathology
• Lymphatic Metastasis
• Male
• Middle Aged
• RNA Interference
• RNA, Small Interfering/metabolism
• Receptors, CXCR/genetics
• Receptors, CXCR/metabolism
• Signal Transduction
• Stomach/pathology
• Stomach Neoplasms/pathology

• Carcinogenesis
• Chronic inflammation
• DNA damage response
• Genomic instability
• Immune response
• Oxidative stress

For many tumors, the overexpression of the chemokine receptor CXCR4 is associated with increased malignancy and poor patient outcomes. However, comprehensive data for neuroendocrine neoplasms of the lung are still lacking.

CXCR4 expression was evaluated in a panel of bronchopulmonary neuroendocrine neoplasms (BP-NEN) comprising typical carcinoids (n = 26), atypical carcinoids (n = 30), and small cell lung cancers (SCLC, n = 34). Samples were analyzed by immunohistochemistry using the novel monoclonal rabbit anti-human CXCR4 antibody UMB-2 and by qRT-PCR. The expression was correlated with clinical data and overall patient survival.

CXCR4 was predominantly localized at the plasma membrane of the tumor cells. CXCR4 was expressed with a high intensity in almost all of the 30 SCLC samples. In contrast, it was detected infrequently and with low intensity in the typical carcinoid and atypical carcinoid samples. There was a significant correlation between the immunohistochemistry and qRT-PCR data. Additionally, there was a significant negative relationship between CXCR4 expression and overall survival.

With increasing malignancy, BP-NEN clearly differ in the extent of CXCR4 expression. As in other tumor entities, CXCR4 overexpression significantly correlates with negative patient outcome. Due to its particular high expression rate in SCLC, CXCR4 may serve as a promising new target for diagnostic and pharmacological intervention as well as for peptide receptor-based radionuclide therapy.

C-X-C chemokine receptor 4 (CXCR4) is frequently over-expressed in various types of cancer; many agents against CXCR4 are in clinical development currently despite variable data for the prognostic impact of CXCR4 expression. Here eighty-five studies with a total of 11,032 subjects were included to explore the association between CXCR4 and progression-free survival (PFS) or overall survival (OS) in subjects with cancer. Pooled analysis shows that CXCR4 over-expression is significantly associated with poorer PFS (HR 2.04; 95% CI, 1.72-2.42) and OS (HR=1.94; 95% CI, 1.71-2.20) irrespective of cancer types. Subgroup analysis indicates significant association between CXCR4 and shorter PFS in hematological malignancy, breast cancer, colorectal cancer, esophageal cancer, renal cancer, gynecologic cancer, pancreatic cancer and liver cancer; the prognostic effects remained consistent across age, risk of bias, levels of adjustment, median follow-up period, geographical area, detection methods, publication year and size of studies. CXCR4 over-expression predicts unfavorable OS in hematological malignancy, breast cancer, colorectal cancer, esophageal cancer, head and neck cancer, renal cancer, lung cancer, gynecologic cancer, liver cancer, prostate cancer and gallbladder cancer; these effects were independence of age, levels of adjustment, publication year, detection methods and follow-up period. In conclusion, CXCR4 over-expression is associated with poor prognosis in cancer.

• CXCR4
• cancer
• meta-analysis
• prognostic biomarker
• survival

Enhancer of zeste 2 (EZH2), a key component of polycomb repressive complex 2 (PRC2), was of great importance in human cancer pathogenesis. Various studies examined the relationship between EZH2 overexpression with the clinical outcome in patients with digestive cancers, but yielded conflicting results. Electronic databases updated to January 2015 were searched to find relevant studies. A meta‐analysis was conducted with eligible studies which quantitatively evaluated the relationship between EZH2 overexpression and survival of patients with digestive cancers. Survival data were aggregated and quantitatively analysed. We performed a meta‐analysis of 10 studies (n = 1461 patients) that evaluated the correlation between EZH2 overexpression and survival in patients with digestive cancers. Combined hazard ratios suggested that EZH2 overexpression was associated with poor prognosis of overall survival (HR = 1.54, 95% CI: 1.27–1.81) in patients with oesophageal cancer. In the stratified analysis, no significant risks were found among gastric cancer (HR = 0.66, 95% CI: 0.16–1.15) and colorectal cancer (HR = 0.91, 0.63–1.19), indicating that EZH2 was not an indicator of poor prognosis in gastric cancer or colorectal cancer. Enhancer of zeste 2 overexpression indicates a poor prognosis for patients with oesophageal cancer, but not among gastric cancer or colorectal cancer.

• colorectal cancer
• enhancer of zeste homolog 2
• gastric cancer
• meta-analysis
• oesophageal cancer
• prognosis

• CXCL12
• CXCR4
• cancer-associated fibroblasts
• gastric cancer
• integrin β1

• Gastric cancer
• Nomogram
• Overall survival
• Prognosis
• Tumor-associated macrophages

• Enhancer of zeste homolog 2
• colorectal cancer
• esophageal cancer
• gastric cancer
• meta-analysis
• prognosis

• CXCL12
• CXCR4
• CXXR4
• Gliomas
• Gliome
• Recurrence pattern
• Récidive

• HOTAIR
• cancer
• digestive system
• lncRNA
• prognosis

Cellular chemotaxis is the best-known function of chemokine receptors which are closely linked with tumor metastasis. In fact, positive expression of chemokine receptors could also be identified even in some patients without metastatic tumors, while the clinical relevance of this data has not been fully established. Our studies were designed to clarify the CCR4 expression profiles and to explore its potential role in histologically node-negative (pN0) gastric cancer (GC). Immunohistochemistry (IHC) or immunohistofluorescence (IHF) analysis was performed on specimens obtained from 108 patients with pN0 GC. We found that CCR4 was aberrantly over-expressed inpN0 GC tissues, with different expression patterns on tumor cells and being associated with T-stage (P = 0.002). The matrigel in vitro invasion assay revealed that over-expression of CCR4 in GC cell lines significantly enhanced the invasive capacity of these cells. Results from real-time RT-PCR and gelatinzymography showed a significant increase in matrix metalloproteinase (MMP)-9 production induced by the forced expression of CCR4 in GC cell lines. Our data suggest that the aberrant CCR4 expression is involved in tumor invasion of pN0 GC and, conceivably, antagonists of CCR4 might be useful candidates for controlling early events in tumor progression.

• Adult
• Aged
• Cell Line, Tumor
• Cell Movement
• Female
• Humans
• Male
• Matrix Metalloproteinase 9/genetics
• Matrix Metalloproteinase 9/metabolism
• Middle Aged
• Neoplasm Invasiveness
• Receptors, CCR4/genetics
• Receptors, CCR4/metabolism
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/pathology
• Up-Regulation

The aim of this study was to reveal the exact changes during the occurrence of breast cancer to explore significant new and promising genes or factors related to this disease.

We compared the gene expression profiles of breast cancer tissues with its uninvolved normal breast tissues as controls using the cDNA microarray analysis in seven breast cancer patients. Further, one representative gene, named IFI30, was quantitatively analyzed by real-time PCR to confirm the result of the cDNA microarray analysis.

A total of 427 genes were identified with significantly differential expression, 221 genes were up-regulated and 206 genes were down-regulated. And the result of cDNA microarray analysis was validated by detection of IFI30 mRNA level changes by real-time PCR. Genes for cell proliferation, cell cycle, cell division, mitosis, apoptosis, and immune response were enriched in the up-regulated genes, while genes for cell adhesion, proteolysis, and transport were significantly enriched in the down-regulated genes in breast cancer tissues compared with normal breast tissues by a gene ontology analysis.

Our present study revealed a range of differentially expressed genes between breast cancer tissues and normal breast tissues, and provide candidate genes for further study focusing on the pathogenesis and new biomarkers for breast cancer.

• Breast neoplasms
• Candidate genes
• Microarray

Aberrant chemokine stromal cell-derived factor 1 (SDF-1) expression has been shown to be involved in the development and progression of various malignancies. Our present study aims to investigate the clinical and prognostic value of SDF-1 expression and improve risk stratification in patients with gastric cancer. Peritumoral and intratumoral SDF-1 levels were assessed in 220 retrospectively enrolled gastric cancer patients, and their relations with clinicopathological features and clinical outcomes were evaluated. A predictive nomogram was created to refine risk stratification for overall survival of gastric cancer patients. Compared with peritumor tissues, tumor tissues showed decreased SDF-1 expression levels according to TNM stage progression in gastric cancer specimens. Peritumoral SDF-1 expression correlated positively with tumor invasion depth and lymph node metastasis, whereas intratumoral SDF-1 expression associated negatively with tumor size, tumor differentiation, tumor invasion depth, lymph node metastasis, and clinical TNM stage. Moreover, both low peritumoral SDF-1 expression and high intratumoral SDF-1 expression indicated favorable overall survival, and SDF-1 risk derived from the peritumoral/intratumoral SDF-1 expression signature could stratify prognosis of patients with gastric cancer. After backward elimination, SDF-1 risk was identified as an independent prognostic factor for survival. Finally, a predictive nomogram was generated with identified independent prognosticators to assess patient survival at 3 and 5 years following surgery. Conclusively, SDF-1 risk, an identified independent prognostic factor, could be developed into a nomogram with tumor invasion depth, lymph node involvement, and distant metastasis to refine predictive accuracy for survival in patients with gastric cancer after surgical resection.

• Gastric cancer
• overall survival
• predictive nomogram
• prognostic biomarker
• stromal cell-derived factor 1

Gastric cancer (GC), which is mainly induced by Helicobacter pylori (H. pylori) infection, is one of the leading causes of cancer-related death in the developing world. Active inflammation initiated by H. pylori infection and maintained by inherent immune disorders promotes carcinogenesis and postoperative recurrence. However, the presence with H. pylori in tumors has been linked to a better prognosis, possibly due to the induction of antitumor immunity. Tumor infiltrations of tumor-associated macrophages, myeloid-derived suppressor cells, neutrophils, Foxp3⁺ regulatory T cells are correlated with poor prognosis. Tumor infiltrating CD8⁺ cytotoxic T lymphocytes, dendritic cells, and CD45RO T cells are generally associated with good prognosis of GC, although some subsets of these immune cells have inverse prognosis prediction values. High ratios of Foxp3⁺/CD4⁺ and Foxp3⁺/CD8⁺ in tumors are associated with a poor prognosis; whereas high Th1/Th2 ratio in tumors predicts a good prognosis. High levels of interleukin (IL)-6, IL-10, IL-32, and chemokine C-C motif ligands (CCL)7 and CCL21 in circulation, high expression of CXC chemokine receptor 4, chemokine C-C motif receptor (CCR)3, CCR4, CCR5, CCR7, hypoxia-inducible factor-1α, signal transducer activator of transcription-3, cyclooxygenase-2, and orphan nuclear receptor 4A2 in tumors are associated with an unfavorable prognosis. Increased serum levels of matrix metalloproteinases (MMP)-3, MMP-7, and MMP-11 and increased levels of MMP-9, MMP-12, and MMP-21 in tumors are consistently associated with poor survival of GC. Further emphasis should be put on the integration of these biomarkers and validation in large cohorts for personalized prediction of GC postoperative prognosis.

• Gastric cancer
• Inflammation
• Biomarker
• Prognosis

• Animals
• Biomarkers, Tumor/metabolism
• Cytokines/metabolism
• Gastritis/complications
• Gastritis/immunology
• Gastritis/metabolism
• Gastritis/microbiology
• Helicobacter Infections/complications
• Helicobacter Infections/immunology
• Helicobacter Infections/metabolism
• Helicobacter Infections/microbiology
• Helicobacter pylori/immunology
• Helicobacter pylori/pathogenicity
• Host-Pathogen Interactions
• Humans
• Inflammation Mediators/metabolism
• Lymphocytes, Tumor-Infiltrating/immunology
• Lymphocytes, Tumor-Infiltrating/metabolism
• Predictive Value of Tests
• Prognosis
• Risk Factors
• Signal Transduction
• Stomach Neoplasms/etiology
• Stomach Neoplasms/immunology
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/microbiology
• Stomach Neoplasms/mortality
• Transcription Factors/metabolism
• Tumor Microenvironment

• polypeptide n-acetylgalactosaminyl transferase-5 (galnac-t5)
• prognostic
• glycosylation
• gastric cancer
• overall survival

• Aged
• Biomarkers, Tumor/genetics
• Disease-Free Survival
• Female
• Gene Expression Regulation, Neoplastic
• Glycosylation
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Molecular Targeted Therapy
• N-Acetylgalactosaminyltransferases/genetics
• Neoplasm Staging
• Prognosis
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/genetics
• Stomach Neoplasms/pathology
• Polypeptide N-acetylgalactosaminyltransferase

Gastric cancer is the fourth most common cancer, and the second-highest cause of cancer-related deaths worldwide. Despite extensive research to identify novel diagnostic and therapeutic agents, patients with advanced gastric cancer suffer from a poor quality of life and poor prognosis, and treatment is dependent mainly on conventional cytotoxic chemotherapy. To improve the quality of life and survival of gastric cancer patients, a better understanding of the underlying molecular pathologies, and their application towards the development of novel targeted therapies, is urgently needed. Chemokines are a group of small proteins associated with cytoskeletal rearrangements, the directional migration of several cell types during development and physiology, and the host immune response via interactions with G-protein coupled receptors. There is also growing evidence to suggest that chemokines not only play a role in the immune system, but are also involved in the development and progression of tumors. In gastric cancer, CXC chemokines and chemokine receptors regulate the trafficking of cells in and out of the tumor microenvironment. CXC chemokines and their receptors can also directly influence tumorigenesis by modulating tumor transformation, survival, growth, invasion and metastasis, as well as indirectly by regulating angiogenesis, and tumor-leukocyte interactions. In this review, we will focus on the roles of CXC chemokines and their receptors in the development, progression, and metastasis of gastric tumors, and discuss their therapeutic potential for gastric cancer.

• Chemokine
• Chemokine receptor
• Gastric neoplasm
• Therapeutic target

• Carcinoma/metabolism
• Carcinoma/therapy
• Cell Survival
• Cell Transformation, Neoplastic
• Chemokines, CXC/metabolism
• Disease Progression
• Humans
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Prognosis
• Quality of Life
• Receptors, Chemokine/metabolism
• Stomach/pathology
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/therapy
• Treatment Outcome
• Tumor Microenvironment

The chemokine receptor CXCR4 plays a significant role in biological processes, as well as in tumorigenesis and the progression of cancer, especially breast cancer. However, the clinical application of CXCR4 for breast cancer prognosis is still very limited. A meta-analysis based on published studies was performed with the aim of obtaining an accurate evaluation of the relationship between CXCR4 expression and the prognosis of breast cancer.

A comprehensive search strategy was used to search relevant literature in PubMed, MEDLINE and the ISI Web of Science. The correlation between CXCR4 expression and clinicopathological features and breast cancer prognosis was analyzed. This meta-analysis was carried out using Review Manager 4.2.

Thirteen eligible studies consisting of 3865 participants were included. We found that breast cancers with CXCR4 expression were associated with lymph node status (pooled RR =1.20, 95% CI: 1.01-1.43, P<0.001) and distant metastasis (pooled RR =1.52, 95% CI: 1.17-1.98, P = 0.125). CXCR4 overexpression was significantly associated with disease free survival (DFS) (RR = 0.77, 95% CI = 0.70–0.86, P = 0.554) and overall survival (OS) (RR = 0.70, 95% CI = 0.59–0.83, P = 0.329). However, there was no significant association between CXCR4 expression and some clinical parameters of breast cancer, such as tumor category, ER status, PR status, or c-erbB-2 status.

Our meta-analysis showed that CXCR4 is an efficient prognostic factor for breast cancer. Overexpression of CXCR4 was significantly associated with lymph node status and distant metastasis and indicated poor overall and disease free survival.