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Copyright ©The Author(s) 2016.
World J Gastroenterol. Jan 21, 2016; 22(3): 1202-1212
Published online Jan 21, 2016. doi: 10.3748/wjg.v22.i3.1202
Table 1 Novel biomarkers in the breakthrough of gastric cancer diagnosis
Biomarkers/proteomics techniquesMethods and InvestigationRef.
MALDI-TOF-MSSpectral peaks for the peptides with (m/z) values of 1741 and 4210 were the most significantly different between precancerous lesions, GC patients and healthy controls and the sensitivity and specificity of this diagnostic model was found to be clinically significantLi et al[19]
SELDICompared to conventional biomarkers CEA, in a micro-particle enzyme immunoassay, 5 distinct protein peaks at 2046, 3179, 1817, 1725 and 1929 m/z were automatically chosen as components of the best biomarker pattern for diagnosis of GC, with a single protein peak at 4665 m/z, which could distinguish between stage I/II and stage III/IV gastric cancer with high specificity and sensitivityLu et al[20]
CTCsClinical researches have already proven than the CTC count can effectively predict prognosis, progression free survival (PFS) and overall survival (OS) for breast, prostate and colorectal cancers with good specificity and high repetition rateDawson et al[27]
piR-651 and piR-823piR-651 and piR-823 are significantly lower in the peripheral blood of gastric cancer patients when compared to normal controlCui et al[29]
miR-421miR-421 level in CTC obtained from peripheral blood of GC patients was significantly higher than that of their control group and the transfection of miR-421 inhibitors could significantly inhibit tumor growth in vivoZhou et al[30]
miR-375 and miR-142-5pmiRNA expression profile in gastric cancer patients indicated that the combination of miR-375 and miR-142-5p could predict recurrence risk for gastric cancer patientsZhang et al[31]
Survivin mRNASurvivin mRNA is an independent prediction factor for disease free survival, whereby a high Survivin mRNA expression after radical tumor resection was an indicator of tumor recurrenceCao et al[34]
B7-H3 mRNAQuantitative RT-PCR confirmed that B7-H3 mRNA was expressed in all 4 GC cell lines and that the 5-yr survival rate of GC patients with high B7-H3 expression was significantly lower than the ones with low expressionArigami et al[35]
miR-21, miR-106a and miR-17miR-21, miR-106a and miR-17 expression patterns showed that the microRNA levels in the GC patients were significantly higher than the control group and the level of microRNA was related to the TNM staging, tumor size and histological classification[38]Zheng et al[36]
MAGE mRNAMAGE-1 and MAGE-3 mRNA is expressed in tumor cells and peripheral blood of GC patients while they are not expressed in the healthy controls; suggesting that MAGE could be a specific tumor marker in the detection of CTCsWang et al[39]
cfDNAcfDNA significantly decreased after surgery and therefore, a decrease in the cfDNA level after surgery would imply positive outcome of the surgery and postoperative treatment while an increase in the cfDNA level would indicate poor outcome or signs of disease progression such as metastasisHuang et al[44], Frattini et al[45], Sozzi et al[46]
cfDNAAs compared to GC patients and advanced GC patients, the level of cfDNA in normal subjects was lower; whereby the level of cfDNA in the 24-h-after-surgery group decreased significantly compared to the pre-operation groupKim et al[47]
cfDNAThe mean level of plasma cfDNA in GC was 2.4-fold higher in the patient group compared with the control group, indicating that plasma cfDNA levels may be useful for predicting patients with gastric cancerPark et al[48]
TP53 mutationsTargeted deep sequencing of plasma cell-free DNA by massively parallel sequencing was performed in patients with tumors harboring TP53 mutations and found detectable TP53 mutation levels in preoperative cfDNA to conclude that ctDNA could serve as a useful biomarker to monitor gastric cancer progression and residual diseaseHawakawa et al[49]
p14 promoter methylationAnalysis of GC specimen found that the rate of methylation of the p14 promoter in invasive GC was 45.5%Leung et al[52]
p15 promoter methylationMethylation of the p15 promoter was present in GC patients whereby there was a higher detection rate of abnormal methylation of MGMT, p15 and mismatch repair gene as compared to healthy controlsLeung et al[52]
MGMT, p15, and Hm-LH1 MethylationThe methylation specific polymerase chain reaction (MSP) method was used to detect the methylation status of MGMT, p15, and Hm-LH1 and found that there was a high detection rate of MGMT, p15 and Hm-LH1 methylation in the plasma of GC, with an even higher methylation detection rate in stages III, IV and distant metastasis GC while there was no abnormal corresponding methylation in the healthy controlsKolesnikova et al[53] Tani et al[54]
p15 and p16 Methylationmethylation-specific PCR was used to investigate the methylation status of p15 and p16 in GC cell lines and tumor tissues and the findings implicated that the inactivation of the multiple tumor suppressor gene p15 and p16 genes was associated with the occurrence of GCLeung et al[55,56]
p16 hyper-methylationMSP was used to investigate the level of p16 in GC and they found out that the correlation of the immune-activity and hyper-methylation of p16 shows that methylation is an important mechanism for the deactivation of p16 in GC and that the inactivation of p16 expression was accompanied by the hyper-methylation of the promoterShim et al[57] Song et al[58]
Runt related transcription factor 3 (Runx3) gene methylationThe pre-operative and post-operative Runt related transcription factor 3 (Runx3) gene methylation level and the results showed that the Runx3 methylation index was related to the tumor grade, tissue type, lymphatic invasion and metastasis and its sensitivity was higher than CEA. On the other hand, the Runx3 methylation level in post-operative serum significantlySakakura et al[63]