Current status of predictive biomarkers for neoadjuvant therapy in esophageal cancer

Table 1 Molecular biomarkers for predicting the response to neoadjuvant therapy in esophageal cancer

Modality/biomarker	N	Histology	Neoadjuvant therapy	Sensitivity	Specificity	PPV	NPV	Accuracy	Ref.
Gene expression profiling
5 genes (EPB41L3, RNPC1, RTKN, STAT5B, and NMES1)	13	Squamous-23%Adeno-77%	CRT; 5-FU and cisplatin, 40.05-44 Gy	100%	91%	NA	NA	95%	[15]
3 genes (PERP, S100A2, and SPRR3)	19	Squamous-11%Adeno-84%	CRT; 5-FU, docetaxel and irinotecan, 50.4 Gy	86%	85%	75%	92%	85%	[16]
Ephrin B3 receptor	47	Adeno-100%	CT; 5-FU, cisplatin and leucovorin	89%	84%	89%	84%	87%	[17]
199 genes	25	Squamous-100%	CT; 5-FU, cisplatin and adriamycin	68%	93%	88%	79%	82%	[18]
32 genes	46	Squamous-46%Adeno-54%	CRT; 5-FU and cisplatin, 35-50 Gy	100%	67%	55%	100%	76%	[19]
Single nucleotide polymorphisms
XRCC1 R399Q	210	Squamous-17%Adeno-83%	CRT; 5-FU, cisplatin and paclitaxel, RT (NA)	NA	NA	NA	NA	NA	[26]
ERCC1 C118T/XRCC1 A194G	52	Squamous-60%Adeno-40%	CRT; 5-FU and cisplatin, 36 Gy	54/5%	67/100%	80/100%	37/59%	58/60%	[27]
MicroRNAs
miR-192, miR-194	8	Squamous-25%Adeno-75%	CRT; 5-FU and cisplatin, 40 Gy	NA	NA	NA	NA	NA	[40]
HS-240, has-miR-296, has-miR-141, has-miR-31, HS-217	25	Squamous-20%Adeno-80%	CRT; cisplatin and irinotecan, 50.4 Gy	NA	NA	NA	NA	NA	[41]
Serum miR-200c	64	Squamous-100%	CT; 5-FU, cisplatin and adriamycin or docetaxel	68%	62%	53%	75%	64%	[43]
miR-200c	98	Squamous-91%	CT; 5-FU, cisplatin and adriamycin	NA	NA	NA	NA	NA	[44]
miR-31	19	Squamous-5%Adeno-95%	CRT; 5-FU and cisplatin, 40.05 Gy	NA	NA	NA	NA	NA	[45]
Proteomics
Mitochondrial respiratory chain complexes	69	Adeno-100%	CT; 5-FU and cisplatin	50%	93%	82%	74%	71%	[53]
C4a, C3a	31	Squamousand adeno; NA	CRT; 5-FU and cisplatin, 40-44 Gy	79%	83%	NA	NA	81%	[54]
Immunohistochemistry
CD44+/CD24-	27	Adeno-100%	CRT; NA	50%	100%	100%	50%	67%	[64]
EGFR	37	Squamous-100%	CT; 5-FU, cisplatin and docetaxel	93%	55%	58%	92%	70%	[65]
HER2/neu	34	Squamous-100%	CRT; 5-FU and cisplatin or leucovorin, 39.6-40 Gy	69%	71%	60%	79%	71%	[66]
p53 (wild-type)	1497	Squamous-91%Adeno-9%	CRT or CT (meta-analysis)	NA	NA	NA	NA	NA	[73]
MLH1, FANCD2	79	Squamous-27%Adeno-71%	CRT; 5-FU, cisplatin and/or paclitaxel, 45-64.8 Gy	20%	100%	100%	22%	35%	[77]
Heat-shock proteins and glucose-regulated proteins	90	Adeno-100%	CT; 5-FU, cisplatin or oxaliplatin	61%	63%	53%	70%	62%	[80]
Serum biomarker
Serum soluble interleukin-6 receptor	37	Squamous-100%	CRT; 5-FU and cisplatin, 40 Gy	NA	NA	NA	NA	NA	[81]
Thymidylate synthetase and dihydropyrimidine dehydrogenase	29	Squamous-34% Adeno-66%	CRT; 5-FU and cisplatin, 36 Gy	20%	100%	100%	36%	45%	[82]
Common blood tests
Neutrophil-to-lymphocyte ratio	83	Squamous-84%	CT; 5-FU and cisplatin	71%	66%	56%	79%	68%	[83]
Albumin	246	Squamous-13%Adeno-86%	CT; cisplatin, epirubicin and 5-FU or capecitabine, or epirubicin and oxaliplatin	NA	NA	NA	NA	NA	[84]

PPV: Positive predict value; NPV: Negative predict value; Squamous: Squamous cell carcinoma; Adeno: Adenocarcinoma; CRT: Chemoradiotherapy; CT: Chemotherapy; 5-FU: 5-fluorouracil; NA: Not available.