Novel biomarkers for early detection of gastric cancer

Table 1 Overview of non-coding RNAs for early detection of GC in the past 5 years

Circulating biomarkers	Alterations	Patients	Controls (normal)	Sample	Methods	Sensitivity (%)	Specificity (%)	AUC	Ref.
miRNA
miR-25	Upregulated	65	65	Plasma	qRT-PCR	87.6	76.9	0.817	[102]
miR-214	Downregulated	168	74	Plasma	qRT-PCR	73.2	91.9	0.880	[103]
miR-376c	Upregulated	47	67	Plasma	qRT-PCR	71.0	78.0	0.77	[104]
miR-381	Downregulated	40	40	Serum	qRT-PCR	83.6	97.5	0.931	[105]
miR-200c	Upregulated	200	250	Tissue and blood	Micoarrayand qRT-PCR	74.0	66.0	0.75	[106]
miR-551b-5p	Downregulated	40	40	Serum	qRT-PCR	77.5	80.0	0.84	[107]
Combination of miR-21, miR-93, miR-106a, and miR-196b	Upregulated	11	17	Plasma	qRT-PCR	84.8	79.2	0.887	[108]
Combination of miR-16, miR-25, miR-92a, miR-451 and miR-486-5p	Upregulated	40	40	Plasma	qRT-PCR	72.9	89.2	0.812	[109]
Combination of miR-4257, miR-6785-5p, miR-187-5p and miR-5739	Upregulated	1417	1417	Serum	microarray analysis	0.996 (index)	0.953 (index)	0998	[23]
Combination of miR-18a, miR-181b, and miR-335	Upregulated	176	173	Serum	qRT-PCR	71.6	87.9	0.86	[95]
Combination of miR-425-5p, miR-1180-3p. miR-122-5p, miR-24-3p and miR-4632-5p	Downregulated	30	90	Plasma	qRT-PCR	NA	NA	0829	[21]
Combination of miRNA-3185, miRNA-6083, miRNA-6792-3p, and miRNA-659-3p	Upregulated	52	30	Plasma	qRT-PCR	NA	NA	0.825	[110]
Combination of miRNA-936, miRNA-1306-3p	Downregulated	52	30	Plasma	qRT-PCR	NA	NA	0.730	[110]
Long non-coding RNAs
ZNFX1-AS1	Upregulated	50	50	Plasma	qRT-PCR	84	68	0.85	[26]
LINC00978	Upregulated	38	31	Serum	qRT-PCR	80	70	0.831	[111]
CTC-501O10.1	Upregulated	100	100	Plasma	qRT-PCR	90	51	0.74	[112]
AC100830.4	Upregulated	100	100	Plasma	qRT-PCR	84	58	0.73	[112]
RP11-210K20.5	Upregulated	100	100	Plasma	qRT-PCR	89	55	0.737	[112]
CTC-497E21.4	Upregulated	110	84	Serum	qRT-PCR	81.8	75.0	0.896	[113]
SNHG17	Upregulated	67	67	Plasma	qRT-PCR	NA	NA	0.748	[114]
ARHGAP27P1	Downregulated	53	53	Plasma	qRT-PCR	75,5	60.4	0.732	[115]
PANDAR	Upregulated	109	106	Plasma	qRT-PCR	NA	NA	0.767	[27]
FOXD2-AS1	Upregulated	109	106	Plasma	qRT-PCR	NA	NA	0.700	[27]
SMARCC2	Upregulated	109	106	Plasma	qRT-PCR	NA	NA	0.748	[27]
LINC00086	Downregulated	168	74	Plasma	qRT-PCR	72.6	83.8	0.86	[103]
B3GALT5-AS1	Upregulated	107	87	Serum	qRT-PCR	87.4	74.7	0.816	[28]
C5orF66-AS1	Downregulated	200	278	Serum	qRT-PCR	77.5	53.6	0.668	[29]
HCP5	Upregulated	98	82	Serum	qRT-PCR	80	70	0.818	[30]
Combined of lnc-MB21D1-3:5, lnc-PSCA-4:2 and lnc-ABCC5-2:1	Upregulated	52	30	Plasma	qRT-PCR	NA	NA	0904	[110]
circular RNAs
has_circ_0000745	Downregulated	60	60	Plasma	qRT-PCR	85.5	45,0	0.683	[33]
circPTPN22	Upregulated	120	104	Plasma	qRT-PCR	78.0	84.0	0.857	[35]
hsa_circ_0001789	Downregulated	24	24	Plasma	qRT-PCR	84.0	50.0	0.82	[34]
8-circRNA biomarker panel	Upregulated	92	46	Serum	qRT-PCR	78.3	78.3	0.87	[36]

miRNA: Micro RNA; qRT-PCR: Quantitative reverse transcriptase polymerase chain reaction; AUC: Area under curve; HCP5: HLA Complex P5; lncRNA: Long non-coding RNA; circ RNA: Circular RNA; NA: Not applicable; ZNFX1-AS1: ZNFX1 antisense RNA 1; PANDAR: Promoter of CDKN1A antisense DNA damage activated RNA; FOXD2-AS1: FOXD2 adjacent opposite strand RNA 1; SMARCC2: SWI/SN F related, matrix associated, actin dependent regulator of chromatin subfamily c member 2; B3GALT5-AS1: B3GALT5 antisense RNA 1; C5orf66-AS1: C5orf66 antisense RNA 1.

Table 2 Overview of exosome associated with early detection of gastric cancer

Marker	Alterations	Patients	Controls (normal)	Sample	Methods	Sensitivity (%)	Specificity (%)	AUC	Ref.
miRNA
miR-590-5p	Downregulated	168	50	Serum	qRT-PCR	63.7	86.0	0.810	[44]
miR-92a-3p	Downregulated	131	122	Serum	qRT-PCR	NA	NA	0.829	[116]
Combination of miR-92b-3p, let-7g-5p, miR-146b-5p, and miR-9-5p	Upregulated	36	12	Serum	qRT-PCR	60	84	0.773	[43]
LncRNA
HOTTIP	Upregulated	126	120	Serum	qRT-PCR	69.8	85.0	0.827	[117]
UEGC1	Upregulated	51	60	Plasma	qRT-PCR	NA	NA	0.876	[39]
Pcsk2-2:1	Upregulated	63	29	Serum	qRT-PCR	84	86.5	0.896	[40]
GNAQ-6:1	Downregulated	43	27	Serum	qRT-PCR	83.7	55.6	0.736	[41]
RNA-GC1	Upregulated	522	219	Serum	qRT-PCR	88.2	82.3	0.90	[42]
piRNAs
piR-019308	Upregulated	70	60	Serum	qRT-PCR	57.14	91.67	0.820	[47]
piR-004918	Upregulated	70	60	Serum	qRT-PCR	42.86	95.0	0.754
piR-018569	Upregulated	70	60	Serum	qRT-PCR	44.29	96.67	0.732

miRNA: MicroRNA; lncRNA: Long non-coding RNA; circRNA: Circular RNA; piRNA: Piwi-interacting RNAs; qRT-PCR: Quantitative reverse transcriptase polymerase chain reaction; NA: Not applicable; GNAQ-6:1: G protein subunit alpha q-6:1.

Table 3 Clinical trials of blood-based biofluid biomarkers for gastric cancer detection

Clinical trials	Type of trial	Phase	Results	Participants (estimated)	Assay	Comments
ctDNA
NCT05027347	Cohort	NA	Recruiting	200	Ultradeep massive parallel sequencing assay	Development of a protocol for detection of ctDNA in plasma of patients with early stages of GC
NCT04511559	Cohort	NA	Not yet recruiting	540	ctDNA methylation sequencing	The correlation between the plasma ctDNA methylation status and the diagnosis of patients with early GC
NCT05208372	Case-control	NA	Recruiting	200	CTC and ctDNA test	Investigation of the value of CTCs and ctDNA in the diagnosis of metastasis of GC in peritoneal flushing fluid and blood
NCT04665687	Cohort	NA	Recruiting	1730	Illumina HiSeq2000/2500-based, MiSeq NGS targeted sequencing	Identification whether tumor’s molecular profiling based on blood could be used for diagnosis of EGC and precancerous gastric adenoma
NCT05029869	Cohort	NA	Recruiting	100	NGS technologies	Study aims to evaluate the use of NGS to detect ctDNA in GC patients after gastrectomy
NCT05224596	Case-control	NA	Recruiting	498	Blood draw and blood-based biomarkers analyses	Multi-omics 498 study aimed at detecting GC by combined assays for serum protein markers, deep sequencing of cfDNA, ctDNA mutation and RNA
miRNAs
NCT04329299	Cohort	NA	Completed	6862	Blood-based biomarkers analyses	Validation of the predictive value of various blood biomarkers, such as miRNA
lncRNAs
NCT05397548	Cohort	NA	Recruiting	700	RT-PCR	Study to investigate the predictive value of circulating exosomal lncRNA-GC1 for early-detection and monitoring progression of GC
Methylation
NCT04511559	Cohort	NA	Not yet recruiting	540	ctDNA methylation sequencing	Methylation analysis of ct DNA in early diagnosis in patients with GC
NCT03076567	Observational	NA	Completed	440	NA	Discovery and validation of plasma DNA methylation biomarker for detection of GC
NCT05336058	Cohort	NA	Recruiting	1240	Multi-target PCR	Exploration of the clinical performance of polygene methylation in the adjunctive diagnosis of GC
NCT04253106	Non-randomized	NA	Recruiting	10	NGS	Activating methylation profiles identified by liquid biopsies could identify CDH1 and CTNNA1 pathogenic variants carriers with DGC
Multi-omics
NCT04947995	Case-control	NA	Recruiting	450	ctDNA multi-omics test	Exploration of a blood-based multi-omics assay and computational model for early detection of GC
NCT05347524	Observational	NA	Recruiting	384	Blood draw and blood-based biomarkers analyses	Detection of peritoneal metastasis of GC by combined assays for methylation of cfDNA and other blood-based biomarkers

GC: Gastric cancer; NGS: Next generation sequencing; PCR: Polymerase chain reaction; DGC: Diffuse gastric cancer; ctDNA: Circulating tumor DNA; cfDNA: Cell-free DNA; miRNA: MicroRNA; lncRNA: Long non-coding RNA; NA: Not applicable; lncRNA-GC1: Gastric cancer-associated lncRNA1.