Table 1 Thirty-eight studies reporting 48 molecules that were associated with clinical survival, recurrence or therapeutic outcome of ESCC patients

BRCA1

Prognosis and chemoradiotherapy

23,326,344

144

Low BRCA1 expression was an independent prognostic factor in cisplatin-based chemotherapy (HR 0.29, 95% CI 0.12–0.71; P = 0.007) or chemoradiotherapy (HR 0.12, 95% CI 0.04–0.37; P < 0.001) group.

CCNA2

Chemotherapy

23,205,070

48

The expression of cyclin A was an independent prognosis factor in patients with ESCC following paclitaxel-based chemotherapy.

CCND1

Prognosis and radiochemotherapy

9,988,238

172

Patients with cyclin D1-positive carcinomas showed significantly worse overall survival than patients with cyclin D1-negative carcinomas (HR 2.14, 95% CI 1.134–3.42; P = 0.0038)

CD163 & CD68

Prognosis and neoadjuvant chemotherapy

25,752,960

210

High infiltration of CD68+ macrophages and CD163+ macrophages was significantly associated with poor prognosis for patients undergoing neoadjuvant chemotherapy (P = 0.057, P = 0.003).

CD274

Prognosis and chemoradiotherapy

26,623,522

45

The higher PD-L1 H-scores had poorer overall survival (median 16.7 versus 32.9 months, P = 0.02) than those with lower H-scores. (HR 2.29, 95% CI 1.12–4.69; P = 0.023)

CD44 & PROM1

Prognosis

27,748,881

47

Patients with strong expression of CD44 or CD133 and those with a high ratio of CD133-positive tumor cells showed significantly poor prognosis regardless of the effect of chemotherapy. PROM1 (HR 5.05, 95% CI 1.12–4.69; P = 0.023)

CDKN2A

neoadjuvant chemotherapy

26,514,506

101

ESCC tumors that were found positive for p16 expression appeared to fall into responders group rather than non responders (P = 0.008) and reported with less mortality (P = 0.048).

CEA & KRT19

Chemoradiotherapy

19,863,186

84

CEA may be helpful in predicting the responsiveness in ESCC of primary lesions to CRT, with the effective rates (CR + PR) in CEA high and low groups of 58.3% (14/24) and 93.3% (56/60), respectively (P = 0.013 and 0.013).

EGFR

Chemoradiotherapy

17,940,077

62

The difference in the CR rate between EGFR positive and -negative groups was significant (CR rate: 62% vs. 34%; P = 0.037).

CRP

Chemoradiotherapy

21,224,533

36

Serum CRP can predict of CRT response with an accuracy of 75%.

ERCC1

Chemotherapy

23,263,828

46

Patients with ERCC1 negative tumors had a higher treatment response than the ERCC1 positive group (radiological response rates; 92.3% vs.50%, P = 0.013).

FAM84B

Neoadjuvant chemoradiation

25,980,316

21

The fold-change of circulating FAM84B mRNA expression can predict the pCR with an AUC of 0.73.

FDXR

Prognosis and Neoadjuvant chemoradiation

26,637,858

50

Fdxr was significantly correlated with postoperative outcomes and an independent prognostic factor (HR 4.950, 95% CI 1.603–15.38; 0.012).

HOXC6 & HOXC8

Prognosis

24,525,058

274

HOXC6 and HOXC8 were independent prognostic factors in patients with ESCC. HOXC6: (HR 1.341, 95% CI 0.895–2.010; P = 0.045); HOXC8: (HR 1.657, 95% CI 1.146–2.395; P = 0.007).

IL6R

Prognosis

23,648,090

218

The sIL6R level was one of several significant independent predictors of an unfavorable outcome. (HR 3.20, 95% CI 1.34–7.53; P = 0.008)

MDM2 & MKI67

Prognosis and chemoradiotherapy

25,880,782

79

MDM2 and p16 are predictive markers for chemoradioresistance in cStageIII ESCC and Ki-67 is a prognostic marker following dCRT in cStageIII ESCC.

MLH1

Prognosis

18,053,639

51

The expression of hMLH1 is a potential marker of tumor response and survival.

MMS19

Chemoradiotherapy

25,892,874

103

High cytoplasmic MMS19 expression was associated with a good response to chemoradiotherapy (OR 11.5, 95% CI: 3.0–44.5; P < 0.001).

MT3

Prognosis

16,351,731

64

Esophageal squamous cell carcinomas with negative p53, positive CDC25B, and negative MT expressions respond well to CRT.

MUC13 & MUC20

Prognosis and neoadjuvant chemotherapy

26,323,930

186

The median survival time of patients with low MUC13/high MUC20 expression was significantly shorter than that of patients with high MUC13/low MUC20 expression (27.7  months vs. 59.5 months, P = 0.021; HR 0.531, 95% CI: 0.299–0.944; P = 0.031).

MUC4

neoadjuvant chemotherapy

26,673,820

186

Low expression of MUC4 and MUC20 in resection samples was significantly correlated with better TRG (tumor regression grade). MUC4 and MUC20 were identified as potential biomarkers for predicting the efficacy of neoadjuvant chemotherapy in ESCC patients.

NOTCH1 & PIK3CA

Prognosis and Chemotherapy

26,528,858

104

NOTCH1 mutations was correlated with shorter survival times and failed to respond to chemotherapy, whereas PIK3CA mutations pointed to better responses to chemotherapy and longer survival times than patients without PIK3CA mutations.

PTGS2

Prognosis and Chemoradiotherapy

21,437,756

58

Negative or weak expression of PTGS2 was correlated significantly with CRT response (OR 6.296, 95% CI 1.58–25.096; P = 0.010).

PTPN6

Prognosis

32,536,826

184

Elevated PTPN6 expression indicated longer OS (HR 1.123, 95% CI: 0.565–2.230; P = 0.741).

RAD51

Prognosis and recurrence

24,065,387

89

Rad51 expression in ESCC was associated with poor survival (P = 0.0324) and recurrence (P = 0.0171).

REG1A

Prognosis

23,645,481

177

REG1A expression was a significant prognostic factor (HR 3.095, 95% CI: 1.569–5.943; P = 0.0015).

SFN

Chemoradiation therapy

15,999,354

62

SFN-positive expressions were closely related to the response to CRT.

Prognosis

24,743,601

278

Downregulation of 14–3-3σpredicts poor survival, suggesting that 14–3-3σmay be a biomarker for early detection of high-risk subjects and diagnosis of ESCC. (HR 0.466, 95% CI 0.251–0.866; P = 0.016).

Prognosis

20,108,042

148

Reduced stratifin expression, T4 stage, lymph node metastasis, and distant metastasis were independent risk factors for worse prognosis in ESCC patients.

SGTA

Prognosis

23,939,810

120

SGTA expression indicated poor prognosis (RR 3.513, 95% CI: 2.161–9.791; P = 0.016).

TGFB1 & VEGFA

Prognosis

24,623,035

79

VEGFA and TGFB1 were significantly associated with pathological response and/or DFS, and may be used to predict pathological response and survivals for ESCC patients receiving combined modality therapy.

TP53 & RRM2B

Prognosis and chemoradiotherapy

15,655,547

62

p53 or p53R2 (RRM2B) expression was correlated with a favorable response to CRT (P = 0.0001 or 0.041 clinical, P = 0.016 or 0.0018 histological, respectively; TP53, RR 2.688, 95% CI: 1.157–6.250; P = 0.0011. RRM2B, RR 2.469, 95% CI: 1.164–5.235; P = 0.0057).

Prognosis

25,135,238

36

The median tumor associated survival was 34.2 months for patients with normal TP53, compared with 8.9 months for those with mutant TP53. The latter had a 3-fold higher risk of death (HR 3.01, 95% CI 1.359–6.86; P = 0.005).

Prognosis

10,414,702

42

The current study indicated that p53 mutation of tumor tissues might be a prognostic factor for esophageal squamous cell carcinoma cases and one of the risk factors for its recurrence.

Chemotherapy

19,941,080

97

Patients with mutations in p53 therefore showed significantly poorer prognosis than those without mutant p53.

RAC3 & TRAM1

Prognosis and chemoradiotherapy

19,552,757

98

Overexpression of AIB1/RAC3/ TRAM1 is a useful predictor of CRT resistance and an independent molecular marker of poor prognosis for ESCC patients.

ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH1L1, ALDH1L2

Prognosis and recurrence

22,847,125

152

ALDH1 was a predictor of postoperative recurrence and prognosis in ESCC, and CD44 might be a predictor of recurrence and prognosis.

PITX2

Prognosis and chemoradiotherapy

23,132,660

454

High expression of PITX2 was associated with poor disease-specific survival (HR 1.732, 95% CI 1.133–2.646; P = 0.011) in ESCC.