Body fluids biomarkers associated with prognosis of acute ischemic stroke: progress and prospects

Figures & data

Figure 1. The candidate prognostic biomarkers of AIS in body fluids.

(A) Schematic diagram of AIS. (B) Network map of 181 keywords, these 181 keywords that appeared more than twice were included and classified into nine clusters in the map by the VOS viewer. (C) AIS prognostic biomarkers in body fluids.

Table 1. Prognostic biomarkers of AIS associated with inflammatory and their prognostic value.

Biomarker	Detection time	Enrolled patients	Prognostic indicator	Ref.
NLR	On admission	First-ever AIS (n = 448)	Unfavorable functional outcome at 3 months (adjusted HR = 2.32)	[18]
Low NLR	After thrombectomy	AIS (n = 142)	Favorable outcomes at 3 months (OR = 0.785)	[20]
NLR	On admission	AIS received EVT (n = 211)	Early neurological deterioration (OR = 1.011)	[25]
PLR	On admission	AIS (n = 363)	Post-stroke depression (OR = 5.145)	[26]
High PLR and high NLR	On admission	First-ever AIS (n = 448)	Unfavorable functional outcome (adjusted HR = 3.77)	[18]
PNR	On admission	AIS (n = 151)	Unfavorable functional outcome (OR = 0.967)	[27]
PNR	24 h after IVT	AIS (n = 151)	Unfavorable functional outcome (OR = 0.933)	[27]
LMR	Before thrombolysis	AIS (n = 591)	Post-thrombolysis early neurological deterioration (OR = 0.680)	[24]
LMR	On admission	AIS (n = 179)	Unfavorable clinical outcome at 3 months (OR = 0.761)	[28]
Low LMR	On admission	AIS (n = 507)	Post-stroke depression (OR = 2.633)	[29]
WMR	On admission	AIS undergone vascular reperfusion surgery (n = 549)	Poor outcome at 3 months (OR = 2.257)	[30]
SII	On admission	AIS (n = 234)	Poor prognosis at discharge (adjusted OR = 2.350)	[31]
SII	On admission	Large vessel occlusion AIS received EVT (n = 379)	Symptomatic intracranial hemorrhage after EVT treatment (OR = 1.005)	[32]
SII	On admission	AIS received IVT (n = 216)	Poor functional outcome at 3-months (OR = 3.953)	[33]
Log-transformed SII	Admitted to ICU	AIS (n = 1181)	30–day all-cause mortality (HR = 2.44)	[34]
SIRI	On admission	AIS received EVT (n = 279)	Poor functional outcome at 3-months (OR = 1.08)	[35]
Low SIRI	On admission	AIS (n = 161)	Favorable outcomes at 3 months (OR = 1.557)	[36]
SIRI	On admission	Mild AIS (n = 240)	Unfavorable functional outcome at 3 months (OR = 2.938)	[37]
SIRI	On admission	AIS (n = 2043)	30–day all-cause mortality (HR = 1.54) 90-day all-cause mortality (HR = 1.56) 1-year all-cause mortality (HR = 1.44)	[38]
WBC	After IVT	AIS (n = 447)	Unfavorable functional outcome at 3 months (adjusted OR = 4.48) 90-day all-cause mortality (adjusted HR = 2.19)	[39]
Low WBC	On admission	AIS received IVT (n = 657)	3–month functional independence (OR = 1.69)	[40]
Leukocytosis 24 h	After IVT	AIS received IVT (n = 213)	Poor short-term functional outcomes (OR = 6.648)	[41]
High PCT	Within 48 h of admission	AIS (n = 748)	30–day all-cause mortality (HR = 5.486)	[42]
IL-5	On admission	First-ever AIS (n = 180)	Poor functional outcome at 3-months (OR = 0.042)	[43]
IL-6	On admission	First-ever AIS (n = 180)	Poor functional outcome at 3-months (OR = 1.293)	[43]
IL-6	After EVT	AIS received EVT (n = 210)	Early neurological deterioration (OR = 1.98)	[44]
IL-10	After EVT	AIS received EVT (n = 210)	Early neurological deterioration (OR = 1.18)	[44]
IL-10	On admission	AIS (n = 350)	Post-stroke depression (adjusted OR = 0.615)	[45]
Low IL-33	On admission	Non-thrombolytic AIS (n = 151)	Hemorrhage transformation (OR = 5.773)	[46]

CRP: C-reactive protein; EVT: Endovascular therapy; HR: Hazard ratio; IVT: Intravenous thrombolysis; LMR: Lymphocyte-to-monocyte ratio; NER: Neutrophil-to-eosinophil ratio; NLR: Neutrophil-lymphocyte ratio; OR: Odds ratio; PLR: Platelet-to-lymphocyte ratio; PNR: Platelet-to-neutrophil ratio; PCT: Procalcitonin; SII: Systemic immune-inflammation index; SIRI: Systemic inflammatory response index; WMR: White blood cell count to mean platelet volume ratio; WBC: White blood cell.

Table 2. Nucleic acid-related prognostic markers of AIS in blood.

Biomarker	Detection time	Enrolled patients	Prognostic indicator	Ref.
miR-124-3p, miR-125b-5p, miR-192-5p	24 h after thrombolysis	AIS (n = 84)	Unfavorable outcomes at 3 months	[63]
miR-9-5p and miR-128-3p	/	AIS (n = 88)	miR-9-5p and miR-128-3p were positively correlated with mRS score (r values were 0.066 and 0.082, respectively)	[65]
miR-491-5p	On admission	AIS (n = 215)	Unfavorable outcomes at 1 year (OR = 0.9)	[66]
miR-206	On admission	AIS (n = 215)	Hemorrhagic transformation (OR = 1.64)	[66]
miRNA-24 and miRNA-29b	/	AIS (n = 105)	miR-24 and miR-29b were negatively correlated with NIHSS score (r values were -0.758 and -0.794, respectively) and mRS score (r values were -0.817 and -0.860, respectively) in elderly AIS patients	[67]
miR-185 and miR-424	On admission	AIS (n = 142)	miR-185 and miR-424 were positively correlated with NIHSS score and mRS score in AIS patients (r values were0.735, 0.802, 0.796, 0.873)	[68]
LncRNA NEAT1	On admission	AIS (n = 210)	RFS in lncRNA NEAT1 high expression patients was shorter compared with lncRNA NEAT1 low expression patients	[69]
LncRNA UCA1	On admission	first-episode AIS (n = 160)	High lncRNA UCA1 expression was associated with worse accumulating RFS in AIS patients	[70]
LncRNA GAS5	On admission	AIS (n = 120)	Elevated lnc-GAS5 was correlated with shorter RFS	[71]
LncRNA HULC	On admission	first-episode AIS (n = 215)	lncRNA HULC high expression predicted worse RFS	[72]
LncRNA NORAD	On admission	AIS (n = 103)	NORAD upregulation was associated with unfavorable prognosis; NORAD was positively correlated with NIHSS scores (r = 0.840)	[73]
LncRNA ZFAS1	On admission	AIS (n = 241)	Lower lnc-ZFAS1 expression relates to increased neurological impairment and inflammation as well as worse RFS in AIS patients	[64]
MALT1	On admission	first-episode AIS (n = 120)	High MALT1 expression independently associated with shorter RFS in AIS patients	[74]
cfDNA	On admission	AIS (n = 54)	Higher cf-DNA levels were associated with poor outcome in AIS patients	[75]

cfDNA: Cell-free DNA; HR: Hazard ratio; MALT1: Mucosa-associated lymphoid tissue lymphoma translocation protein 1; OR: Odds ratio; r: Person correlation coefficient.

Table 3. Prognostic biomarkers in urine, saliva, and CSF.

Biomarker		Detection time	Enrolled patients	Relative prognostic value	Ref.
Urine	Urinary protein	On admission	AIS (n = 2842)	Patients with positive urinary protein was associated with a 2.74-fold and 1.62-fold increase in the risk of in-hospital mortality (adjusted HR = 2.74)	[105]
	UACR	On admission	AIS (n = 294)	Early neurological deterioration was positively associated with high UACR (≥39.6 mg/g creatinine)	[101]
	Urinary ketone	On admission	AIS or transient ischemic attack (n = 14015)	30–day all-cause mortality (HR = 2.44), Poor functional outcomes (OR = 1.85	[104]
	Urinary titin	Immediately after admission, and on days 3, 5, and 7	AIS (n = 41)	The peak urinary titin level was associated with the mRS score (r = 0.55), the NIHSS score (r = 0.72), and the Barthel index (r = -0.59) upon hospital discharge	[106]
Saliva	g_Streptococcus, g_Prevotella, g_Veillonella, and g_Fusobacterium	2 h after ischemic stroke	AIS (n = 146)	The higher the abundance of two specific microorganisms, the worse the prognosis of AIS patients at 3 months	[108]
CSF	Tau	On admission	AIS (n = 50)	CSF tau was also significantly correlated with mRS score at 12 months after stroke (r = 0.403)	[109]
	GFAP, S100B	On admission	AIS (n = 89)	GFAP and S100B concentrations correlated with mRS score at month 3 (r = 0.42 and r = 0.28, respectively).	[110]
	CSF/plasma proCPU ratio	Hyperacute phase	AIS (n = 72) or transient ischemic attack (n = 14)	statistically significant correlations of the proCPU ratio with mRS score and mortality at month 3 (r = 0.30 and r = 0.31, respectively)	[111]

CSF: Cerebrospinal fluid; GFAP: Glial fibrillary astrocytic protein; HR: Hazard ratio; OR: Odds ratio; proCPU: Procarboxypeptidase U; r: Person correlation coefficient; Tau: Microtubule-associated protein tau; UACR: Urinary albumin/creatinine ratio.

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