Association of survivin splice variants with prognosis and treatment of breast cancer

Table 1 Summarized data from research articles that examined the expression of survivin transcript variants (used method is provided) accordingly to clinicopathological characteristics of patients and their survival

Ref.	Examined variants	Methods	Association with patient characteristics	Conclusion
Végran et al[22]	wt, sur2b, surΔΕx3, sur3b, sur2a	Real time qPCR	Tumor grade, estrogen receptors, lymph nodes	High expression sur3b tumors had shorter OS and DFS
Span et al[23]	wt, sur2b, surΔΕx3, sur3b, sur2a	Reverse transcription qPCR	Age, tumor grade, lymph nodes, steroid hormone receptors	High expression of sur2a, sur3b and wt indicate poorer prognosis
Ryan et al[10]	wt, sur2b, surΔΕx3	Reverse transcription qPCR, Western blotting	Tumor size, nodal metastases, breast cancer type	Wt and surΔΕx3 were correlated posively with apoptosis
Pavlidou et al[4]	wt, sur2b, surΔΕx3	Real time qPCR	Tumor grade, estrogen receptors	Sur2b/wt had significant association with estrogen receptors
Athanassiadou et al[24]	wt	Immunocytochemistry, immunohistochemistry	Grade, lymph nodes, tumor size	increased wt may indicate a worse prognosis

wt: Wild-type surviving; sur2b: Survivin-2b; surΔΕx3: Survivin-ΔΕx3; sur3b: Survivin-3b; sur2a: Survivin-2a; qPCR: Quantitative polymerase chain reaction; OS: Overall survival; DFS: Disease free survival.

Table 2 Panel of 21 genes used in oncotype DX breast cancer assay

Proliferation group	Invasion group	Estrogen group	HER2 group		Reference genes
Ki-671	ST3	ER	GRB7 (growth factor receptor-bound protein 7)	GSTM11	ACTB1
STK151	CTSL2	PR1	HER2 [human EGF (epidermal growth factor) receptor 2]	CD68	GAPDH1
BIRC5 (Survivin)1		Bcl2			RPLPO1
CCNB11		SCUBE2 [Signal peptide CUB (complement proteins C1r/C1s, Uegf, and Bmp 1)-EGF domain-containing protein 2]		BAG1	GUS1
MYBL21					TFRC1

¹Genes used in 12-gene oncotype DX for ductal carcinoma in situ. ER: Estrogen receptor; PR: Progesterone receptor; Bcl2: B-cell CLL/lymphoma 2; ST3: Stromelysin 3; CTSL2: Cathepsin L2; Ki-67: Kinase inhibitor; STK15: Serine/threonine kinase 15; CCNB1: Cyclin B1; MYBL2: Myeloblastosis family transcription factor-like 2; ACTB: Beta-actin; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; RPLPO: Ribosomal phosphoprotein; GUS: β-glucuronidase; TFRC: Transferrin receptor; GSTM1: Glutathione S-transferase M1 gene; CD68: CD68 molecule; BAG1: Bcl2–associated athanogene 1.

Table 3 Summarized data for research articles, which correlated survivin isoforms with breast cancer treatment

Ref.	Examined variants	Methods	Approaches for inhibition of survivin variants	Conclusion
Yamanaka et al[55]	wt, sur2b, surΔΕx3, sur3b	Real time qPCR	YM155	Survivin suppressing activity of YM155 may offer novel therapeutic option in TNBC
Boidot et al[57]	wt, sur2b, surΔΕx3, sur3b, sur2a	Real time qPCR	FEC/Tax-Epi	Alternative survivin transcript expression levels may be predictive markers in FEC and Tax-Epi treatment
Zheng et al[58]	wt, sur2b, surΔΕx3	MMT, flow cytmetry	Recombinant plasmids pGEM-T	Feasibility of targeting wt and surΔΕx3 in treating breast cancer

wt: Wild-type surviving; sur2b: Survivin-2b; surΔΕx3: Survivin-ΔΕx3; sur3b: Survivin-3b; sur2a: Survivin-2a; MMT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; YM155: Sepantronium bromide; FEC: 5-fluorouracil + epirubicin + cyclophosphamide; Tax-Epi: Docetaxel + epirubicin; TNBC: Triple negative breast cancer.