Cancer-derived exosomes as novel biomarkers in metastatic gastrointestinal cancer

Zhong, Danyang; Wang, Ziyuan; Ye, Zhichao; Wang, Yifan; Cai, Xiujun

doi:10.1186/s12943-024-01948-6

Molecular Cancer

Table 1 Potential exosomal biomarkers in GIC metastasis and their mechanism

From: Cancer-derived exosomes as novel biomarkers in metastatic gastrointestinal cancer

Cancer type	Exosomal Contents	Exosome Source	Exosomal Cargo	Effect	Clinical Significance	Ref
colorectal cancer	miRNA	Cell culture fluid	miR-29a	downregulate the expression of ZO-1, Claudin-5, and Occludin via targeting KLF4	promote metastasis	[66]
		Cell culture fluid	miR-218-5p	activate the Ras/ERK/c-Fos pathway	promote metastasis	[110]
		Cell culture fluid	miR-181b-3p	downregulate SNX2 expression	promote metastasis	[111]
		serum	miR-92a-3p	inhibit FBXW7 and MOAP1	promote metastasis	[104]
		Cell culture fluid	miR-27b-3p	activate STAT3 pathway	promote metastasis	[113]
		Cell culture fluid	miR-203a-3p	inhibit the Src/PKC/GSK-3β	promote metastasis	[108]
		Serum	miRNA132-5p, miRNA6087, and miRNA320d	not mention	promote metastasis	[189]
		Serum	miR-146a-5p and miR-155-5p	activate JAK2–STAT3/NF-κB signaling	promote metastasis	[43]
		Cell culture fluid	miRNA-335-5p	overexpress of RASA1	promote metastasis	[190]
		Serum	miR-122	not mention	promote metastasis	[191]
		Serum	miR-141-3p and miR-375	not mention	promote metastasis	[91]
		Serum	miR-106b-3p	downregulate DLC-1 expression	promote metastasis	[92]
		Serum	miR-1246/92b-3p/27a-3p	target GSK3β and activate the Wnt/β-catenin pathway	promote metastasis	[65]
		Serum	miR-193a and let-7 g	not mention	promote metastasis	[192]
		Serum	miR-128-3p	activate TGF-β/SMAD and JAK/STAT3 signal pathway	promote metastasis	[102]
		Cell culture fluid	miR-106b-5p	downregulate PDCD4 and activate the PI3Kγ/AKT/mTOR signaling pathway	promote metastasis	[193]
		Cell culture fluid	miR-21-5p	suppress VHL/ HIF-1α axis, target TrkA/ERK/ELK1 pathway	promote metastasis	[194]
		Serum	miR-934	downregulate PTEN expression and activate the PI3K/AKT signaling pathway	promote metastasis	[195]
		Serum	miR-25-3p, miR-130b-3p, miR-425-5p	activate of the CXCL12/CXCR4/PTEN/PI3K/Akt pathway axis	promote metastasis	[196]
		Serum	miR- 221/222	suppress SPINT1 expression	promote metastasis	[94]
		Serum	miR-1229	inhibit the expression of HIPK2, activate VEGF pathway	promote metastasis	[197]
		Cell culture fluid	miR-183-5p	suppress FOXO1 expression	promote metastasis	[112]
	circRNA	serum	circPABPC1	upregulate HMGA2, BMP4 and ADAM19 expression	promote metastasis	[139]
		Serum	circ_FMN2	serve as miR-338-3p Sponge to downregulate MSI1	promote metastasis	[198]
		Cell culture fluid	circPACRGL	facilitate the TGF-β1 expression, regulate miR-142-3p/miR-506-3p-TGF-β1 axis	promote metastasis	[199]
		Tissue	circLONP2	not mention	promote metastasis	[140]
		Cell culture fluid	circ-ABCC1	activate the Wnt/β-catenin pathway	promote metastasis	[200]
		serum	circ-133	activate the miR-133a/GEF-H1/RhoA axis	promote metastasis	[136]
		serum	circGAPVD1	not mention	promote metastasis	[142]
		serum	circTUBGCP4	activate Akt signaling pathway, sponge with miR-146b-3p	promote metastasis	[135]
		serum	hsa-circ-0004771	not mention	promote metastasis	[201]
		Cell culture fluid	ciRS-122	ciRS-122-miR-122-PKM2 pathway	promote metastasis	[151]
		serum	circCOG2	Activate the miR-1305/TGF-β2/SMAD3 pathway	promote metastasis	[202]
		Cell culture fluid	circLPAR1	suppress the METTL3-eIF3h interaction, decrease the translation of oncogene BRD4	promote metastasis	[203]
	lncRNA	Cell culture fluid	lnc-HOXB8-1:2	bind hsa-miR-6825-5p to upregulate CXCR3 expression	promote metastasis	[204]
		Cell culture fluid	lncRNA RPPH1	interact with protein TUBB3	promote metastasis	[122]
		serum	lncRNA PVT1/VEGFA	downregulate miR-152-3p	promote metastasis	[120]
		Cell culture fluid	lncRNA PCAT1	activate of the miR-329-3p/Netrin-1-CD146 Complex	promote metastasis	[127]
		Cell culture fluid	lncRNA BANCR	regulate RhoA/ROCK signaling	promote metastasis	[205]
		Cell culture fluid	lncRNA MALAT1	sponge miR-26a/26b and activate PI3K/Akt/mTOR pathway	promote metastasis	[128]
		Cell culture fluid	lncRNA UCA1	sponge with miR-143	promote metastasis	[117]
	proteins	serum	ADAM17	cleaving the E-cadherin junction	promote metastasis	[69]
		serum	HSPC111	activate CXCL5-CXCR2 axis	promote metastasis	[68]
		serum	KRAS	not mention	promote metastasis	[71]
		serum	Cyr61	activate αV β5 /FAK/HIF-1α/STAT3/MMP2 signaling	promote metastasis	[83]
		Cell culture fluid	FMNL2	activate the EGFL6/CKAP4/ERK axis	promote metastasis	[84]
		Cell culture fluid	ADAM17	not mention	promote metastasis	[70]
hepatocellular cancer	miRNA	serum	miR-200b-3p	activate JAK/STAT signaling pathway	promote metastasis	[95]
		liver tissue	miR-20a-5p	downregulate LIMA1-Mediated β-Catenin Pathway	promote metastasis	[44]
		Cell culture fluid	miR-412,36 miR-4286,37 miR-423–5p, and miR-29a-5p,	impair lysosome biogenesis	promote metastasis	[206]
		Cell culture fluid	miR-452-5p	downregulate TIMP3	promote metastasis	[207]
		serum	miR92a-3	inhibit PTEN and activating Akt/Snail signaling	promote metastasis	[107]
		Cell culture fluid	miR-21 and miR-10b	not mention	promote metastasis	[208]
		serum	miR-18a, miR-20b, and miR-221	not mention	promote metastasis	[96]
		serum	miR-1307-5p	downregulate miR-1307-5p/SEC14L2/Akt and miR-1307-5p/ENG signaling pathways	promote metastasis	[97]
		Cell culture fluid	miR-1273f	activate the Wnt/β-catenin signaling, and downregulate LHX6	promote metastasis	[209]
		Cell culture fluid	miR-100-5p	downregulate CLDN11, activate PI3K/AKT signaling pathway	promote metastasis	[210]
		serum	miR-4661-5p	not mention	promote metastasis	[101]
	circRNA	Cell culture fluid	circ_002136	downregulate miR-19a-3p/RAB1A pathway	promote metastasis	[211]
		serum	circCCAR1	upregulate WTAP	promote metastasis	[149]
		Cell culture fluid	circ_0003028	activate miR-498/ODC1 signaling axis, sponge miR-498,	promote metastasis	[212]
		Cell culture fluid	circ_MMP2	upregulate of its host gene MMP2 via sponging of miR-136-5p	promote metastasis	[213]
		HCC tissues	circTTLL5	activate miR-136-5p/KIAA1522 axis, sponge miR-136-5p	promote metastasis	[137]
		serum	circRNA-100338	activate of MMP9, regulate VM formation	promote metastasis	[214]
		serum	circGSE1	activate the miR‐324‐5p/TGFBR1/Smad3 axis	promote metastasis	[215]
		serum	CircANTXR1	activate miR-532-5p/XRCC5 axis	promote metastasis	[216]
		HCC tissues	CircPAK1	bind 14–3–3 ζ with YAP	promote metastasis	[217]
		Cell culture fluid	circPTGR1	activate miR449a-MET pathway	promote metastasis	[141]
		Cell culture fluid	Circ-0000284	not mention	promote metastasis	[134]
		plasma	circUHRF1	inhibit NK cell function	promote metastasis	[150]
		Plasma	hsa_circ_0004277	inhibit of ZO-1	promote metastasis	[48]
		Cell culture fluid	hsa_circ_0074854	mediate macrophage M2 polarization	promote metastasis	[58]
		Cell culture fluid	CircRNA Cdr1as	promote the expression of AFP and sponge with miR-1270	promote metastasis	[218]
		Cell culture fluid	circTMEM181	inhibit the ATP-adenosine pathway, increase the expression of CD39	promote metastasis	[60]
		serum	Circ-ZNF652	vie miR-29a-3p/guanylyl cyclase domain containing 1 axis	promote metastasis	[219]
	lncRNA	serum	LINC00161	inhibiting miR-590-3p to activate the ROCK2 signaling pathway	promote metastasis	[119]
		serum	lncRNA THEMIS2- 211	activate THEMIS2-211/miR-940/SPOCK1 axis	promote metastasis	[121]
		serum	lncRNA SNHG16	activate miR-942-3p/MMP9 axis	promote metastasis	[124]
		Cell culture fluid	lncRNA H19	activate miR-520a-3p/LIMK1 axis	promote metastasis	[220]
		Cell culture fluid	lncRNA HCG18	downregulate miR-424-5p/SOX9 axis and PI3K/AKT pathway	promote metastasis	[221]
		serum	lncRNAENSG00000248932.1, ENST00000440688.1 and ENST00000457302.2	not mention	promote metastasis	[222]
	proteins	Cell culture fluid	CTLA-4	activate PTEN/CD44 signal pathway	promote metastasis	[85]
		Cell culture fluid	S100A4	activate STAT3 phosphorylation and up-regulating OPN expression	promote metastasis	[74]
		Cell culture fluid	BMI1	not mention	promote metastasis	[79]
		tumor tissue	LOXL4	activate the FAK/Src pathway	promote metastasis	[82]
		Cell culture fluid	ENO1	activate the FAK/Src-p38MAPK pathway	promote metastasis	[81]
		Cell culture fluid	RAB13	upregulate VEGF and activity of CUX1	promote metastasis	[223]
		Cell culture fluid	RAB5A	not mention	promote metastasis	[224]
gastric cancer	miRNA	peritoneal lavage	hsa-let-7 g-3p and hsa-miR-10395-3p	activate the TGFβ signaling pathway	promote metastasis	[225]
		Cell culture fluid	MiR-374a-5p	activate NF-κB signaling	promote metastasis	[226]
		serum	miR-519a-3p	activate the MAPK/ERK pathway by targeting DUSP2	promote metastasis	[98]
		Cell culture fluid	miR-106a	inhibit the expression of Smad7	promote metastasis	[227, 228]
		Cell culture fluid	miR-21-5p	activate TGF-β/Smad pathway	promote metastasis	[229]
		serum	miR-10b-5p, miR-101-3p and miR143-5p	not mention	promote metastasis	[114]
		serum	miR-301a-3p	activate MiR-301a-3p/PHD3/HIF-1α signaling axis	promote metastasis	[230]
		Cell culture fluid	miR-501-5p	downregulate of BLID, subsequent inactivate of caspase-9/-3 and phosphorylate of Akt	promote metastasis	[231]
		serum	miR-379-5p and miR-410-3p	not mention	promote metastasis	[99]
		Cell culture fluid	miR-486-5p	downregulate SMAD2, CDK4, and ACTR3	promote metastasis	[232]
		serum	hsa‐miR‐148‐3p, hsa‐miR‐335‐5p, hsa‐miR‐3613‐5p, and hsa‐miR‐556‐5p	not mention	promote metastasis	[233]
		Peritoneal lavage fluid	miR-21-5p, miR-92a-3p, miR-223-3p, and miR-342-3p	not mention	promote metastasis	[106]
		serum	miR-196a-1	inhibit SFRP1 protein expression	promote metastasis	[234]
		serum	miR-1307-3p、piR-019308、piR-004918, piR-018569	not mention	promote metastasis	[100]
	circRNA	serum	circ_0038138	downregulate miR-198/EZH2 axis	promote metastasis	[235]
		serum	circFCHO2	activate the JAK1/STAT3 pathway via sponging miR-194-5p	promote metastasis	[236]
		Tumour tissues	circNRIP1	activate AKT1/mTOR pathway, sponge of miR-149-5p	promote metastasis	[47]
		serum	circNEK9	activate miR-409-3p/MAP7 axis	promote metastasis	[133]
		serum	Hsa_circ_0000437	upregulate SRSF3, activate HSPA2-ERK signaling pathway	promote metastasis	[138]
		serum	circ-RanGAP1	activate miR-877-3p/VEGFA axis	promote metastasis	[143]
		serum	circSHKBP1	activate the miR-582-3p/HUR/VEGF pathway	promote metastasis	[144]
		Cell culture fluid	circular RNA UBE2Q2	via the circUBE2Q2-miR-370-3p-STAT3 axis	promote metastasis	[237]
		Cell culture fluid	circular RNA circ_0032821	sponge with miR-515-5p to regulate SOX9 expression	promote metastasis	[238]
		serum	circ-PVT1	by miR-30a-5p/YAP1 axis	promote metastasis	[239]
	lncRNA	Cell culture fluid	lncRNA HOTTIP	activate microRNA-885-3p/EphB2 axis	promote metastasis	[240]
		serum	lnc-SLC2A12-10:1	not mention	promote metastasis	[241]
		Cell culture fluid	lncRNA PCGEM1	reduce the degradation of SNAI1	promote metastasis	[126]
		tumor tissue	lncRNA SPRY4-IT1	activate SPRY4-IT1/miR-101-3p/AMPK axis	promote metastasis	[118]
		Cell culture fluid	lncRNA TTN-AS1	activate miR-499a-5p/ZEB1/CDX2 axis	promote metastasis	[125]
		tumor tissue	lncRNA LINC01091	activate miR-128-3p/ELF4/CDX2 axis	promote metastasis	[109]
		serum	lncRNA X26nt	decrease vascular endothelial cadherin	promote metastasis	[242]
	proteins	peritoneal lavage fluid	NNMT	activate TGF-β/smad2 signal pathway	promote metastasis	[75]
		serum	Wnt5a	inhibit of YAP signal pathway	promote metastasis	[72]
		serum	IntegrinB5	activate PI3K-AKT pathways	promote metastasis	[73]
pancreatic cancer	miRNA	Cell culture fluid	miR-125b-5p	activate of MEK2/ERK2 signaling	promote metastasis	[243]
		serum	miR-3960	suppress TFAP2A/PTEN/AKT signaling pathway	promote metastasis	[244]
		Cell culture fluid	miR-27a	induce angiogenesis by inhibiting BTG2 expression	promote metastasis	[245]
		Cell culture fluid	miR-501-3p	decrease TGFBR3 levels and activate TGF-βpathway	promote metastasis	[246]
	circRNA	serum	circ-IARS	sponge with miR-122	promote metastasis	[145]
		Cell culture fluid	circ-PED8A	upregulate MET, sponge with miR-338, activate MACC/MET/ERK or AKT pathways	promote metastasis	[146]
		serum	circZNF91	MiRNA sponge for miR-23b-3p	promote metastasis	[152]
	proteins	serum	EphA2	not mention	promote metastasis	[247]
		Cell culture fluid	CD44v6/C1QBP complex	activate of IGF-1 signal	promote metastasis	[76]
		serum	APOE	not mention	promote metastasis	[248]
		Cell culture fluid	Eps8	not mention	promote metastasis	[78]
		Cell culture fluid	ASPH	activate Notch signaling	promote metastasis	[86]
		serum	DNAJB11	activate the EGFR/MAPK pathway	promote metastasis	[87]
		serum	CCT8, CTSL, SAA1, IGF2	not mention	promote metastasis	[88]
		cancer tissue	FGD5-AS1	activate STAT3/NF-κB signaling pathway	promote metastasis	[89]
		serum	Lin28B	activate the Lin28B/let-7/HMGA2/PDGFB signaling pathway	promote metastasis	[90]
		Cell culture fluid	ZIP4	not mention	promote metastasis	[249]
		serum	PRKD-1	increase in F-actin	promote metastasis	[250]
		Cell culture fluid	DYRK1A	stabilize the c-MET receptor through SPRY2, lead to prolonged activate of extracellular signal-regulated kinase signaling	promote metastasis	[77]

Abbreviations: TGF-β1 transforming growth factor-β1, VM vasculogenic mimicry, VEGF vascular endothelial-derived growth factor, IGF-1 insulin-like growth factor 1, DYRK1A Dual-specificity tyrosine regulated kinase 1A, SPRY2 Sprouty 2, HUR human antigen R

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