Research ArticleOriginal Article

Somatic copy number alterations are predictive of progression-free survival in patients with lung adenocarcinoma undergoing radiotherapy

Fan Kou, Lei Wu, Yan Guo, Bailu Zhang, Baihui Li, Ziqi Huang, Xiubao Ren and Lili Yang
Cancer Biology & Medicine May 2022, 19 (5) 685-695; DOI: https://doi.org/10.20892/j.issn.2095-3941.2020.0728

Article Figures & Data

Figures

  • Figure 1
    Figure 1

    Survival analysis with respect to SCNAs in patients with NSCLC undergoing radiotherapy from TCGA and validation cohort. (A) OS and PFS in patients with NSCLC undergoing radiotherapy from TCGA cohort. (B) OS and PFS in patients with LUAD from TCGA cohort. (C) OS and PFS in patients with LUSC from TCGA cohort. (D) OS and PFS in patients with LUAD from the validation cohort. *P < 0.05.

  • Figure 2
    Figure 2

    The distribution of SCNAs in different histologic subtypes and TNM stages. (A) Distribution of SCNA levels in LUAD and LUSC. (B) Distribution of SCNA levels in 4 TNM stages. (C) Comparison of SCNA levels among TNM stages I–IV in patients with LUAD. (D) Comparison of SCNA levels among TNM stages I–IV in patients with LUSC. *P < 0.05.

  • Figure 3
    Figure 3

    Survival analysis of SCNAs in patients with LUAD undergoing radiotherapy, according to TNM stage. (A) OS and PFS in stage I. (B) OS and PFS in stage II. (C) OS and PFS in stage III. (D) OS and PFS in stage IV. *P < 0.05.

  • Figure 4
    Figure 4

    Prognostic nomogram for patients with LUAD undergoing radiotherapy. (A) Nomogram showing the assessment of PFS with SCNAs and TNM. (B) Nomogram for predicting 1-year, 3-year, and 5-year PFS in the RT-LUAD cohort. Calibration plot showing the AUC of the predictive model for PFS. (C) Calibration curve for predicting PFS at 1 year, 3 years, and 5 years in patients with LUAD.

  • Figure 5
    Figure 5

    Underlying pathways in patients with LUAD with high vs. low SCNA levels. (A & B) GSEA used to identify KEGG in the low SCNA group and high SCNA group, respectively. According to the false discovery rate q-value, the 5 most significant pathways are shown. (C) Association of the key genes in the cell cycle pathway with SCNAs in the low and high SCNA groups in TCGA cohort. (D) Expression levels of the key genes in the cell cycle pathway (PRKDC, CHEK1, CDC25A, ORC6, and MCM3) in the low and high SCNA groups in TCGA cohort. (E) Expression levels of the key genes in the cell cycle pathway (PRKDC, CHEK1, CDC25A, ORC6, and MCM3) in the low and high SCNA groups, detected in 15 patients with LUAD by RT-qPCR. Significance is given as *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001.

Tables

  • Table 1

    Clinical characteristics of patients with LUAD undergoing radiotherapy (n = 20)

    CharacteristicsLUAD (n = 20)
    Gender, n (%)
     Male9 (45.00%)
     Female11 (55.00%)
    Age, y, n (%)
     < 609 (45.00%)
     ≥ 6011 (55.00%)
    Tumor stage, n (%)
     I5 (25.00%)
     II7 (35.00%)
     III7 (35.00%)
     IV1 (5.00%)
    Progression, n (%)
     No3 (15.00%)
     Yes17 (85.00%)
    Survival, n (%)
     No9 (45.00%)
     Yes10 (50.00%)
     NA1 (5.00%)
  • Table 2

    Clinical characteristics of patients undergoing radiotherapy

    CharacteristicsTotal (n = 486)LUAD (n = 226)LUSC (n = 260)
    Gender, n (%)
     Male185 (38.07%)109 (48.23%)192 (73.85%)
     Female301 (61.93%)117 (51.77%)68 (26.15%)
    Age, y, n (%)
     < 60103 (21.19%)60 (26.55%)43 (16.54%)
     ≥ 60374 (76.96%)161 (71.24%)213 (81.92%)
     NA9 (1.85%)5 (2.21%)4 (1.54%)
    Tumor stage, n (%)
     I258 (53.09%)133 (58.85%)125 (48.08%)
     II135 (27.78%)47 (20.80%)88 (33.84%)
     III70 (14.40%)29 (12.83%)41 (15.77%)
     IV16 (3.29%)12 (5.31%)4 (1.54%)
     NA7 (1.44%)5 (2.21%)2 (0.77%)
    NSCLC, n (%)
     LUAD226 (46.50%)226 (100%)0
     LUSC260 (53.50%)0260 (100%)
    Progression, n (%)
     No322 (66.26%)135 (59.73%)187 (71.92%)
     Yes260 (33.74%)91 (40.27%)73 (28.08%)
    Survival, n (%)
     No186 (38.27%)78 (34.51%)108 (41.54%)
     Yes300 (61.73%)148 (65.49%)152 (58.46%)
  • Table 3

    Factors associated with PFS in patients with LUAD undergoing radiotherapy (n = 216)

    CharacteristicsHR (95% CI)P value
    Univariate analysis
     Gender (male vs. female)0.8646 (0.5654–1.322)0.5020
     Age (< 60 vs. ≥ 60)1.2771 (0.767–2.126)0.3470
     SCNA (low vs. high)2.0948 (1.366–3.211)0.0007*
     TNM (I vs. II)1.8650 (1.1305–3.077)0.0147*
     TNM (I vs. III)1.2912 (0.6514–2.559)0.4642
     TNM (I vs. IV)2.2676 (0.9634–5.337)0.0608
    Multivariate analysis
     Gender (male vs. female)0.8253 (0.5325–1.279)0.3902
     Age (< 60 vs. ≥ 60)1.4474 (0.8628–2.428)0.1613
     SCNA (low vs. high)2.0756 (1.3264–3.248)0.0014*
     TNM (I vs. II)1.5938 (0.9552–2.659)0.0743
     TNM (I vs. III)1.3074 (0.6570–2.602)0.4452
     TNM (I vs. IVa)1.7708 (0.7350–4.266)0.2028

    *P < 0.05 was considered significant.

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