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Table 1 Liquid biopsies based molecular determinants of BrM in various cancers

From: Liquid biopsies to occult brain metastasis

S. No.

Sample

Cancer Type

Molecular Determinants

Readout

Reference

1

CTCs/Blood/ (N = 10)

BC

EpCAM (+ve) /Notch Signaling

Upregulation in Notch Signaling

[33]

2

CTCs/ctDNA/ Blood/(N = 10)

LC

NRF2

Mutations in NRF2 (R34G)

[34]

3

CTCs/Blood/(N = 4)

BC

Semaphorin 4D/GPX1/MYC

High expression of SEMA4D, GPX1 and MYC gene amplification

[35]

4

CTCs/Blood/(N = 38)

BC

HER2+/EGFR+/HPSE+/NOTCH1+

Brain metastasis selected markers

[36]

5

CTCs/Pleural effusion/(N = 3)

BC

ST6GALNAC5

The high expression of ST6GALNAC5 facilitates co-option and passage through BBB

[37, 38]

6

CTCs/CSF/(N = 13)

BC

Syndecan-1 and MUC-1

Overexpression of syndecan-1 and MUC-1 in Leptomeningeal metastasis

[39]

7

ctDNA/Serum/(N = 311)

NSCLC

EGFR

BrM associated with the EGFR mutation and in concordance with EGFR status in tissues

[40]

8

ctDNA/Blood/(N = 28)

Metastatic Brain tumor

ALK, MDM2

BrM associated with the ALK and MDM2 mutation

[41]

9

ctDNA/Blood/(N = 70)

BC

miR124-2; miR3193; CCDC8

BrM associated with miR124-2, CCDC8 hypermethylation, and miR3193 hypomethylation

[42]

10

ctDNA/Blood/(N = 205)

LC

TGF-ß1

rs1982073 mutant

[43]

11

ctDNA/CSF/(N = 21;12)

LC

EGFR

> 50% patients have EGFR mutations

[44, 45]

12

ctDNA/Blood/(N = 92)

Melanoma

BRAF/NRAS

BRAF (V600E/K/D); NRAS (Q61R/L)

[46]

13

Protein/Serum/(N = 379)

LC

Cathepsin F/ Fibulin-1

Cathepsin upregulates in LC patients’ serum

[47]

14

Protein/Serum/(N = 29)

Brain Metastatic

C-Reactive Protein

C-reactive protein was upregulated in brain metastatic patients’ blood as compared to glioblastoma

[48]

15

Protein/Serum/(N = 120)

LC

IL6

Elevated IL6 in serum associated with BrM

[49]

16

Protein/Serum/(N = 30)

LC

S100ß

Serum has significantly high S100ß

[50]

17

Protein/Serum/(N = 68)

LC

Myelin

Myelin is high in serum

[51]

18

Protein/CSF/(N = 45)

Leukemia

sVEGFR-1,2

Elevated serum levels of sVEGFR-2

[52]

19

Protein/Serum/(N = 147)

BC

Glial fibrillary acidic protein

Elevated serum levels of GFAP

[53]

20

Protein/Serum/(N = 244)

BC

Tau

Elevated serum levels of Tau

[54]

21

Protein/Serum/(N = 68)

LC

Neurofilament Light Chain

Elevated serum levels of NFL

[55]

22

Protein/Serum/(N = 103)

BC

CXCL13; CX3CL1

CXCL13 and CX3CL1 enhances BBB permeability

[56]

23

Exosome/(N = 75)

LC

Integrinβ3

BrM occurs in patients with high EV ITGβ3 levels

[57]

24

Exosome/(N = 104)

BC

CEMIP

Tumor derived exosomes enriched in CEMIP protein promoted BrM

[58]

25

Exosome/(N = 6)

LC

miR-550a35p

miR-550a-3-5p controls the BrM

[59]

26

Exosome/(N = 38)

BC

miR-105

Cancer secreted miR-105 destroys BBB

[60]

27

Exosome/(N = 65)

LC

miR-335-5p/miR-34b-3p

miR-335-5p & miR-34b-3p are unique in BrM

[61]

28

Exosome/(N = 56)

BC

miR-181c/miR-503/miR-105

Enriches exosomes promotes BrM

[62, 63]

29

Serum/CSF/(N = 118)

BC

miR-200a, miR-200b, miR-200c, miR-141

Upregulated in BrM

[64]

30

Serum/(N = 24)

SCLC

LncRNA XR_429159.1

Downregulated in BrM

[65]