Prognostic impact of biomarkers in NSCLC patients treated with complete resection with or without ACT
| First author [ref.] | Subjects n | Treatment | Stage | Method | Biomarker | Biomarker expression | Disease-free survival | Overall survival | ||||
| Survival | p-value | Survival | p-value | |||||||||
| Univariate | Multivariate | Univariate | Multivariate | |||||||||
| Ilie [13] | 632, only SCC | ACT (type: NA) or OP# | I–III | IHC | iNTR | Low | 43 months | <0.0001 | NA | 60 months | <0.0001 | NA |
| High | 34 months | 46 months | ||||||||||
| Sève [14] | 265 | ACT (CDDP + NVB) or OP¶ | IB–II | IHC | TUBB3 | High | HR: 1.52 (1.05–2.22) | 0.03 | 0.03 | HR: 1.39 (0.96–2.01) | 0.08 | 0.07 |
| Low | NA | NA | NA | NA | NA | NA | ||||||
| Reiman [15] | 1149 | ACT (CDDP + NVB) or OP¶ | I–III | IHC | TUBB3 | High | HR: 1.30 (1.11–1.53) | NA | 0.001 | HR: 1.27 (1.07–1.51) | NA | 0.008 |
| Low | 1 (reference) | NA | 1 (reference) | NA | ||||||||
| Okuda [16] | 50 | ACT (CDDP-based) or OP# | I–III | IHC | TUBB3 | Positive | NA | NA | NA | 27% | 0.0303 | NA |
| Negative | NA | NA | NA | 74.6% | NA | |||||||
| Pesta [17] | 22, only ADC | ACT (platinum-based) or OP# | I–III | RT-PCR | RRM1 | High | NA | NA | NA | 803 days | NA | 0.033 |
| Low | NA | NA | NA | 386 days | NA | |||||||
| Pesta [17] | 16 | ACT (platinum-based) or OP# | III | RT-PCR | RRM1 | High | 643 days | NA | 0.033 | NA | NA | NA |
| Low | 144 days | NA | NA | NA | NA | |||||||
| Olaussen [18] | 761 | ACT (CDDP-based) or OP¶ | I–III | IHC | ERCC1 | High | NA | NA | NA | HR: 0.66 (0.49–0.90) | NA | 0.009 |
| Low | NA | NA | NA | 1 (reference) | NA | |||||||
| Pesta [17] | 14, only SCC | ACT (platinum-based) or OP# | III | RT-PCR | ERCC1 | High | 337 days | NA | 0.044 | NA | NA | NA |
| Low | 128 days | NA | NA | NA | NA | |||||||
| Leng [19] | 85 | ACT (platinum-based)+ | I–IV | PCR | ERCC1 | Low | >42.6 months | 0.001 | 0.018 | >42.6 months | 0.001 | 0.027 |
| High | 15.4 months | 20.9 months | ||||||||||
| Cubukcu [20] | 44 | ACT (platinum-based)+ | I–IIIB | IHC | ERCC1 | Low | 27 months | <0.05 | <0.05 | 33 months | <0.05 | <0.05 |
| High | 13 months | 20 months | ||||||||||
| Pierceall [21] | 426, only SCC | ACT (CDDP-based) or OP¶ | I–III | IHC | ERCC1 | High | HR: 0.66 (0.45–0.96) | 0.01 | 0.03 | HR: 0.71 (0.48–1.03) | 0.07 | 0.15 |
| Low | 1 (reference) | 1 (reference) | ||||||||||
| Okuda [16] | 90 | ACT (CDDP- based) or OP# | I–III | IHC | ERCC1 | Positive | NA | NA | NA | 37.6% | 0.0068 | NA |
| Negative | NA | NA | NA | 60.8% HR: 2.18 (1.16–4.01) | 0.0145 | NA | ||||||
| Pesta [17] | 10 | ACT (platinum-based) or OP# | I | RT-PCR | BRCA1 | High | NA | NA | NA | Longer OS | NA | 0.03 |
| Graziano [22] | 250 | ACT (CBDCA + Pacl) or OP¶ | IB | IHC | p53 | Positive | HR: 1.95 (1.26–3.02) | NA | 0.0029 | HR: 2.30 (1.44–3.67) | NA | 0.0005 |
| Negative | 1 (reference) | NA | 1 (reference) | NA | ||||||||
| Pierceall [21] | 426, only SCC | ACT (CDDP-based) or OP¶ | I–III | IHC | p53 | High | HR: 0.72 (0.5–1.03) | NA | 0.08 | HR: 0.69 (0.48–1.00) | 0.03 | 0.05 |
| Low | 1 (reference) | NA | 1 (reference) | |||||||||
| Tsao [23] | 253 | ACT (CDDP-NVB) or OP¶ | IB–II | IHC | p53 | Positive | NA | NA | NA | HR: 1.89 (1.07–3.34) | 0.03 | 0.02 |
| Negative | NA | NA | NA | 1 (reference) | ||||||||
| Filipits [24] | 782 | ACT (CDDP-based) or OP¶ | I–III | IHC | MRP2 | Positive | NA | NA | NA | 40% | 0.007 | NA |
| Negative | NA | NA | NA | 45% HR: 1.37 (1.09–1.72) | ||||||||
| Kamal [25] | 673 | ACT (CDDP-based) or OP¶ | I–III | IHC | MSH2 | High | NA | NA | NA | 58 months | 0.01 | NA |
| Low | NA | NA | NA | 42 months HR: 0.66 (0.49–0.90) | NA | |||||||
| Pierceall [21] | 426, only SCC | ACT (CDDP-based) or OP¶ | I–III | IHC | MSH2 | High | HR: 0.67 (0.47–0.96) | 0.03 | 0.14 | HR: 0.89 (0.52–1.28) | 0.18 | 0.52 |
| Low | 1 (reference) | 1 (reference) | ||||||||||
| Nakano [26] | 151 | ACT (UFT)+ | I–III | IHC | TS | Negative | NA | NA | NA | HR: 2.663 | NA | 0.0003 |
| Positive | NA | NA | NA | 1 (reference) | NA | |||||||
| Miyoshi [27] | 54 | ACT (UFT)+ | I–II | IHC | TS | Negative | NA | NA | NA | 89.5% | 0.001 | NA |
| Positive | NA | NA | NA | 50.0% | NA | |||||||
| Graziano [22] | 250 | ACT (CBDCA + Pacl) or OP¶ | IB | IHC | Mucin | Positive | HR: 2.05 (1.31–3.21) | NA | 0.0018 | HR: 2.03 (1.26–3.26) | NA | 0.004 |
| Negative | 1 (reference) | NA | 1 (reference) | NA | ||||||||
| Leng [19] | 85 | ACT (platinum-based)+ | I–IV | PCR | BAG-1 | Low | >42.6 months | 0.001 | 0.017 | >42.6 months | 0.001 | 0.022 |
| High | 12.9 months | 17.0 months | ||||||||||
| Shi [28] | 144 | ACT (Pacl-, Gem-, NVB- or Doc- based) or OP# | I–III | IHC | pERK1/2 | Positive | NR | 0.01 | NA | NA | NA | NA |
| Negative | 21.1 months HR: 0.33 (0.18–0.61) | 0.001 | ||||||||||
| Shi [28] | 144 | ACT (Pacl-, Gem-, NVB- or Doc- based) or OP# | I–III | IHC | pAkt-1 | Positive | 15.7 months | 0.021 | NA | NA | NA | NA |
| Negative | 48.2 months HR: 1.76 (1.11–2.79) | 0.016 | ||||||||||
| Voortman [29] | 639 | ACT (CDDP-based) or OP¶ | I–III | RT-PCR | Micro-RNA | Negative | NA | NA | NA | 47 months | 0.06 (p-trend: 0.01) | NA |
| Positive | NA | NA | NA | 59 months HR: 0.81 (0.65–1.01) | NA | |||||||
| Yan [30] | 151 | ACT (Pacl-, Gem-, NVB- or Doc-based)+ | I–III | IHC | TopIIA | High | HR: 0.44 (0.24–0.82) | NA | 0.009 | NA | NA | NA |
| Low | NA | NA | NA | NA | NA | |||||||
Survival data are presented as time, hazard ratios (HR) (95% CI) or % 5-year survival. NSCLC: nonsmall cell lung cancer; ACT: adjuvant chemotherapy; SCC: squamous cell carcinoma; NA: not available; OP: complete surgery only; IHC: immunohistochemistry; iNTR: intratumoral CD66b+ neutrophil/CD8+ lymphocyte ratio; CDDP: cisplatin; NVB: vinorelbine; TUBB3: β-tubulin class III; ADC: adenocarcinoma; RT-PCR: reverse transcriptase PCR; RRM1: ribonucleoside-diphosphate reductase large subunit; ERCC1: excision repair cross-complementation group 1; BRCA1: breast cancer susceptibility gene 1; OS: overall survival; CBDCA: carboplatin; Pacl: paclitaxel; MRP2: multidrug resistance protein 2; MSH2: MutS homologue 2; UFT: uracil-tegafur; TS: thymidylate synthase; BAG-1: BCL2-associated athanogene; Gem: gemcitabine; Doc: docetaxel; pERK1/2: extracellular signal-regulated kinase 1/2; NR: not reached; pAkt-1: protein kinase B; TopIIA: topoisomerase II-α. #: not randomised patients, ACT group and OP group (control group); ¶: randomised trial, ACT group and OP group (control group); +: not randomised patients, only ACT patients.