A systematic review of miRNAs as biomarkers for chemotherapy-induced cardiotoxicity in breast cancer patients reveals potentially clinically informative panels as well as key challenges in miRNA research

Brown, Cameron; Mantzaris, Michael; Nicolaou, Elpiniki; Karanasiou, Georgia; Papageorgiou, Elisavet; Curigliano, Giuseppe; Cardinale, Daniela; Filippatos, Gerasimos; Memos, Nikolaos; Naka, Katerina K.; Papakostantinou, Andri; Vogazianos, Paris; Ioulianou, Erietta; Shammas, Christos; Constantinidou, Anastasia; Tozzi, Federica; Fotiadis, Dimitrios I.; Antoniades, Athos

doi:10.1186/s40959-022-00142-1

Table 1 List of microRNA’s targeted by studies of breast cancer patients displaying cardiotoxicity following treatment with Anthracyclines and comparison of expression with control groups

From: A systematic review of miRNAs as biomarkers for chemotherapy-induced cardiotoxicity in breast cancer patients reveals potentially clinically informative panels as well as key challenges in miRNA research

MicroRNA	Reference	Subjects (Healthy Controls/ Chemotherapy group)	Treatment	Period Tested	Expression Change to Control group	Differential Expression	Proposed Role
Section A
hsa-miR-29a-3p	[33]	17/17	DOX	6 months	Increased	+ 5 RE	Cardiac repair
hsa-miR-199a-3p	[28]	38/7	NAC	2 cycles	Increased	+ 1.2 FC	Cardiomyocyte regeneration
hsa-miR-1273 g-3p	[34]	20/20	AC	PT	Decreased	−0.52Log₂ΔCt	Regulatory function of TGF-β pathway
hsa-miR-4638-3p	[34]	20/20	AC	PT	Decreased	−1.37 Log₂ΔCt	Regulatory function of TGF-β pathway
Section B
hsa-miR-34a-5p	[33]	17/17	DOX	6 months	Increased	+ 40 RE	Cardiac repair
	[28]	38/7	NAC	2 cycles	Increased	+ 24.3 FC
	[32]	44/12	DOX	3 months	No significant change	–
	[32]	14/18	EPI	3 months	No significant change	–
hsa-miR-1	[31]	46/10	DOX	4 cycles	Increased	+ 2Log₂FC	Cardiac hypertrophy
	[28]	38/7	NAC	3 months	No significant change	–
	[32]	44/12	DOX	3 months	No significant change	–
	[32]	14/18	EPI	3 months	No significant change	–
hsa-miR-17-5p	[29]	170/9	EC-D	8 cycles	No significant change	–	Pro-angiogenic
hsa-miR-17-5p	[30]	346/19	EC-D	8 cycles	Decreased	0.213 OR
hsa-miR-19a	[29]	170/9	EC-D	8 cycles	Increased	+ 2.1 RE	Pro-angiogenic
hsa-miR-19a	[30]	346/19	EC-D	8 cycles	No significant change	–
hsa-miR-122-5p	[32]	44/12	DOX	3 months	Increased	+ 3 ΔΔCt	Coronary disease
hsa-miR-122-5p	[32]	14/18	EPI	3 months	No significant change	–
hsa-miR-130a	[29]	170/9	EC-D	8 cycles	No significant change	–	Cardiomyopathy
	[30]	346/19	EC-D	8 cycles	No significant change	–
	[35]	60/12	EC-D + T	15 months	Increased	+ 4 RE
hsa-miR-378	[29]	170/9	EC-D	8 cycles	No significant change	–	Pro-angiogenic
hsa-miR-378	[30]	346/19	EC-D	8 cycles	Decreased	0.278 OR
hsa-miR-423	[28]	38/7	NAC	3 months	Increased	+ 1.3 FC	Progressive heart failure
	[31]	46/10	DOX	4 cycles	No significant change	–
	[33]	17/17	DOX	6 months	Increased	+ 6.5 RE
hsa-miR-499	[32]	44/12	DOX	3 months	Increased	+ 2 ΔΔCt	Acute myocardial infarction
	[28]	38/7	NAC	3 months	No significant change	–
	[32]	14/18	EPI	3 months	No significant change	–
	[33]	17/17	DOX	6 months	Increased	+ 15 RE
hsa-miR-885-5p	[32]	44/12	DOX	3 months	Increased	+ 2 ΔΔCt	Liver toxicity
hsa-miR-885-5p	[32]	14/18	EPI	3 months	No significant change	–
Section C
hsa-Let-7b	[29]	170/9	EC-D	8 cycles	No significant change	–	Pro-angiogenic
hsa-Let-7b	[30]	346/19	EC-D	8 cycles	No significant change	–
hsa-miR-17-3p	[29]	170/9	EC-D	8 cycles	No significant change	–	Cardiac hypertrophy
hsa-miR-17-3p	[30]	346/19	EC-D	8 cycles	No significant change	–
hsa-miR-18a	[29]	170/9	EC-D	8 cycles	No significant change	–	Oncogenic inhibitor
hsa-miR-18a	[30]	346/19	EC-D	8 cycles	No significant change	–	in breast cancer
hsa-miR-19b-1	[29]	170/9	EC-D	8 cycles	No significant change	–	Inflammatory
hsa-miR-19b-1	[30]	346/19	EC-D	8 cycles	No significant change	–	response
hsa-miR-92a	[29]	170/9	EC-D	8 cycles	No significant change	–	Pro-angiogenic
hsa-miR-92a	[30]	346/19	EC-D	8 cycles	No significant change	–
hsa-miR-133a	[28]	38/7	NAC	3 months	No significant change	–	Acute myocardial infarction
hsa-miR-133b	[31]	46/10	DOX	4 cycles	No significant change	–	Acute myocardial
hsa-miR-133b	[28]	38/7	NAC	3 months	No significant change	–	infarction
hsa-miR-146a	[31]	46/10	DOX	4 cycles	No significant change	–	Inflammatory response
hsa-miR-208a	[28]	38/7	NAC	3 months	No significant change	–	Cardiomyocyte
hsa-miR-208a	[31]	46/10	DOX	4 cycles	No significant change	–	damage
hsa-miR-208b	[28]	38/7	NAC	3 months	No significant change	–	Cardiomyocyte
hsa-miR-208b	[31]	46/10	DOX	4 cycles	No significant change	–	damage
hsa-miR-296	[29]	170/9	EC-D	8 cycles	No significant change	–	Angiogenesis
hsa-miR-296	[30]	346/19	EC-D	8 cycles	No significant change	–
Section D
hsa-miR-20a	[29]	170/9	EC-D	8 cycles	Increased	+ 1.1 RE	Pro-angiogenic
hsa-miR-20a	[30]	346/19	EC-D	8 cycles	Decreased	0.264 OR
hsa-Let-7f	[29]	170/9	EC-D	8 cycles	Increased	+ 1.1 RE	Pro-angiogenic
hsa-Let-7f	[30]	346/19	EC-D	8 cycles	Decreased	0.228 OR
hsa-miR-126	[29]	170/9	EC-D	8 cycles	Increased	+ 1.5 RE	Pro-angiogenic
	[33]	17/17	DOX	6 months	Increased	+ 28 RE
	[30]	346/19	EC-D	8 cycles	Decreased	0.358 OR
	[28]	38/7	NAC	3 months	Increased	+ 1.3 FC
hsa-miR-210	[29]	170/9	EC-D	8 cycles	Increased	+ 1.2 RE	Pro-angiogenic
hsa-miR-210	[30]	346/19	EC-D	8 cycles	Decreased	0.475 OR

Part A: microRNAs with significant changes in expression with no independent replication, Part B: microRNAs with significant changes in expression and independent replication (whether significant or not), Part C: microRNAs with no significant changes in expression detected, Part D: microRNAs with contradictory evidence of direction of expression change in independent replication. Key: EC-D = Epirubicin + Cyclophosphamide (4 cycles) followed by Docetaxel (4 cycles), DOX = Doxorubicin, EPI = Epirubicin, NAC = Cyclophosphamide + Epirubicin (4 cycles) followed by Paclitaxel (9 to 12 weeks), AC = Anthracycline chemotherapy (not specified), PT = Post-treatment, RE = Relative Expression, FC = Fold Change, OR = Odds Ratio

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