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pmid:32795325

Bioinformatic analysis revealing mitotic spindle assembly regulated NDC80 and MAD2L1 as prognostic biomarkers in non-small cell lung cancer development.

Rong Wei · Ziyue Wang · Yaping Zhang · Bin Wang · Ningning Shen · Li E · Xin Li · Lifang Shang · Yangwei Shang · Wenpeng Yan · Xiaoqin Zhang · Wenxia Ma · Chen Wang

BMC medical genomics · 2020 doi:10.1186/s12920-020-00762-5

Paper

complete

Experiment

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Data

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Analysis

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
id
pmid:32795325
kind
science-record
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sha256:7bba95a0f90d1ee96f91a018d33bb4c7fcf607b78c73cb3738f8b1a6acec66c6
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https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json
created_at
2026-11-01T15:41:07Z
updated_at
2026-11-01T22:02:02Z
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paper object · 10 fields
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title
Bioinformatic analysis revealing mitotic spindle assembly regulated NDC80 and MAD2L1 as prognostic biomarkers in non-small cell lung cancer development.
doi
10.1186/s12920-020-00762-5
pmid
32795325
authors array · 13 items
[0]
Rong Wei
[1]
Ziyue Wang
[2]
Yaping Zhang
[3]
Bin Wang
[4]
Ningning Shen
[5]
Li E
[6]
Xin Li
[7]
Lifang Shang
[8]
Yangwei Shang
[9]
Wenpeng Yan
[10]
Xiaoqin Zhang
[11]
Wenxia Ma
[12]
Chen Wang
journal
BMC medical genomics
year
2020
abstract
BACKGROUND: Lung cancer has been the leading cause of tumor related death, and 80% ~ 85% of it is non-small cell lung cancer (NSCLC). Even with the rising molecular targeted therapies, for example EGFR, ROS1 and ALK, the treatment is still challenging. The study is to identify credible responsible genes during the development of NSCLC using bioinformatic analysis, developing new prognostic biomarkers and potential gene targets to the disease. METHODS: Firstly, three genes expression profiles GSE44077, GSE18842 and GSE33532 were picked from Gene Expression Omnibus (GEO) to analyze the genes with different expression level (GDEs) between NSCLC and normal lung samples, and the cellular location, molecular function and the biology pathways the GDEs enriched in were analyzed. Then, gene function modules of GDEs were explored based on the protein-protein interaction network (PPI), and the top module which contains most genes was identified, followed by containing genes annotation and survival analysis. Moreover, multivariate cox regression analysis was performed in addition to the Kaplan meier survival to narrow down the key genes scale. Further, the clinical pathological features of the picked key genes were explored using TCGA data. RESULTS: Three GEO profiles shared a total of 664 GDEs, including 232 up-regulated and 432 down-regulated genes. Based on the GDEs PPI network, the top function module containing a total of 69 genes was identified, and 31 of 69 genes were mitotic cell cycle regulation related. And survival analysis of the 31 genes revealed that 17/31 genes statistical significantly related to NSCLC overall survival, including 4 spindle assembly checkpoints, namely NDC80, BUB1B, MAD2L1 and AURKA. Further, multivariate cox regression analysis identified NDC80 and MAD2L1 as independent prognostic indicators in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) respectively. Interestingly, pearson correlation analysis indicated strong connection between the four genes NDC80, BUB1B, MAD2L1 and AURKA, and their clinical pathological features were addressed. CONCLUSIONS: Using bioinformatic analysis of GEO combined with TCGA data, we revealed two independent prognostic indicators in LUAD and LUSC respectively and analyzed their clinical features. However, more detailed experiments and clinical trials are needed to verify their drug targets role in clinical medical use.
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And then multivariate COX regression analysis was performed using TCGA mRNA transcription data including 223 lung adenocarcinoma and 482 lung squamous cell carcinoma, which were downloaded from TCGA database [24] to identify the independent prognostic indicators from the univariate significant gene lists.
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sections[8] "Survival analysis of module genes to identify key genes" paragraph 3
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And then multivariate COX regression analysis was performed using TCGA mRNA transcription data including 223 lung adenocarcinoma and 482 lung squamous cell carcinoma, which were downloaded from TCGA database [24] to identify the independent prognostic indicators from the univariate significant gene lists.
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the published estimate and its evidence
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Signaling pathways that Cluster 1 genes mainly enriched in
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Function module analysis based on PPI network
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Signaling pathways that Cluster 1 genes mainly enriched in
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pathways
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count
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Related GDEs in the network
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Cell Cycle, Mitotic
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31
[2]
2.76403E-29
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CENPE; KNTC1; KIF18A; TOP2A; MAD2L1; CCNB2; CKS1B; MCM4; CCNB1; PTTG1; NUF2; CDK1; AURKA; PLK1; TYMS; CCNA2; CDC20; NDC80; BUB1; CDC6; GINS2; CDC45; PLK4; CDCA8; KIF20A; RRM2; KIF2C; RFC4; KIF23; CENPF; NEK2;
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22
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1.71367E-18
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CENPE; KNTC1; KIF18A; MAD2L1; MCM4; NUF2; CDK1; PLK1; CDC20; NDC80; BUB1; CDC6; GINS2; CDC45; PLK4; CDCA8; KIF20A; KIF2C; RFC4; KIF23; CENPF; NEK2;
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Mitotic M-M/G1 phases
[1]
20
[2]
1.48601E-16
[3]
CENPE; KNTC1; KIF18A; MAD2L1; MCM4; NUF2; CDK1; PLK1; CDC20; NDC80; BUB1; CDC6; CDC45; PLK4; CDCA8; KIF20A; KIF2C; KIF23; CENPF; NEK2;
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5.76137E-16
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Polo-like kinase signaling events in the cell cycle
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14
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2.77681E-14
[3]
CENPE; CCNB1; CDK1; AURKA; TPX2; ECT2; PLK1; PRC1; CDC20; NDC80; BUB1; PLK4; DLGAP5; KIF20A;
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13
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3.83583E-13
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Mitotic Prometaphase
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12
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5.11023E-12
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CENPE; KNTC1; KIF18A; MAD2L1; NUF2; PLK1; CDC20; NDC80; BUB1; CDCA8; KIF2C; CENPF;
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Cell Cycle Checkpoints
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11
[2]
1.32039E-08
[3]
MAD2L1; CCNB2; MCM4; NDC80; CCNB1; CDK1; CDC20; CDC6; CDC45; RFC4; CHEK1;
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[0]
Signaling by Aurora kinases
[1]
11
[2]
1.04137E-10
[3]
NCAPH; NCAPG; AURKA; TPX2; NDC80; BUB1; CDCA8; DLGAP5; KIF20A; KIF2C; KIF23;
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Multivariate cox regression analysis on LUAD overall survival
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Survival analysis of cluster 1 module genes
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Table 2
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Multivariate cox regression analysis on LUAD overall survival
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Lung adenocarcinoma
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[1]
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Mo vs M1
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2.321
[2]
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[0]
NDC80 expression
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[0]
< median vs > median
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2.480
[2]
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Multivariate cox regression analysis on LUSC overall survival
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PMC7437940
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14
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Survival analysis of cluster 1 module genes
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Table 3
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Multivariate cox regression analysis on LUSC overall survival
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Lung squamous cell carcinoma
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Hazard ratio
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MAD2L1 expression
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The association between NDC80 and LUAD clinical pathological features
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PMC7437940
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15
section_title
NDC80 and MAD2L1 association with NSCLC clinical features
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table object · 8 fields
label
Table 4
caption
The association between NDC80 and LUAD clinical pathological features
rows array · 29 items
[0] array · 3 items
[0]
parameters
[1]
NDC80
[2]
P value
[1] array · 2 items
[0]
–
[1]
+
[2] array · 2 items
[0]
Gender
[1]
P = 0.209
[3] array · 3 items
[0]
male
[1]
45 (45.9%)
[2]
53 (54.1%)
[4] array · 3 items
[0]
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[1]
68 (54.4%)
[2]
57 (45.6%)
[5] array · 2 items
[0]
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[1]
P = 0.027
[6] array · 3 items
[0]
< 60 years old
[1]
24 (39.3%)
[2]
37 (60.7%)
[7] array · 3 items
[0]
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[1]
82 (56.2%)
[2]
64 (43.8%)
[8] array · 2 items
[0]
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[1]
P = 0.002
[9] array · 3 items
[0]
no
[1]
23 (65.7%)
[2]
12 (34.3%)
[10] array · 3 items
[0]
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[2]
31 (67.4%)
[11] array · 3 items
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[1]
39 (59.1%)
[2]
27 (40.9%)
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P = 0.032
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[1]
66 (57.4%)
[2]
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[1]
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[2]
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[2]
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[1]
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[2]
4 (44.4%)
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[1]
P = 0.199
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[1]
37 (61.7%)
[2]
23 (38.3%)
[20] array · 3 items
[0]
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[1]
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[2]
68 (52.3%)
[21] array · 3 items
[0]
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[1]
7 (41.2%)
[2]
10 (58.8%)
[22] array · 3 items
[0]
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[1]
6 (40.0%)
[2]
9 (60.0%)
[23] array · 2 items
[0]
N
[1]
P = 0.053
[24] array · 3 items
[0]
-
[1]
69 (56.6%)
[2]
53 (43.4%)
[25] array · 3 items
[0]
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[1]
44 (43.6%)
[2]
57 (56.4%)
[26] array · 2 items
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[1]
P = 0.497
[27] array · 3 items
[0]
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[1]
81 (50.9%)
[2]
78 (49.1%)
[28] array · 3 items
[0]
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[1]
27 (45.8%)
[2]
31 (54.2%)
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section[15]/table-wrap[1]#Tab4
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The association between MAD2L1 and LUSC clinical pathological features
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pmcid
PMC7437940
section_index
15
section_title
NDC80 and MAD2L1 association with NSCLC clinical features
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Table 5
caption
The association between MAD2L1 and LUSC clinical pathological features
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[0] array · 3 items
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[1]
MAD2L1
[2]
P value
[1] array · 2 items
[0]
–
[1]
+
[2] array · 2 items
[0]
Gender
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P = 0.097
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[0]
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[1]
170 (47.8%)
[2]
186 (52.2%)
[4] array · 3 items
[0]
female
[1]
71 (56.3%)
[2]
55 (43.7%)
[5] array · 2 items
[0]
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[1]
P = 0.100
[6] array · 3 items
[0]
< 60 years old
[1]
44 (42.7%)
[2]
59 (57.3%)
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[0]
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[1]
192 (51.9%)
[2]
178 (48.1%)
[8] array · 2 items
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[1]
P = 0.973
[9] array · 3 items
[0]
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[1]
131 (50.6%)
[2]
128 (49.4%)
[10] array · 3 items
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28 (50.0%)
[2]
28 (50.0%)
[11] array · 3 items
[0]
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[1]
82 (49.4%)
[2]
84 (50.6%)
[12] array · 2 items
[0]
Stage
[1]
P = 0.062
[13] array · 3 items
[0]
I
[1]
132 (56.2%)
[2]
103 (43.8%)
[14] array · 3 items
[0]
II
[1]
70 (44.6%)
[2]
87 (55.4%)
[15] array · 3 items
[0]
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35 (42.7%)
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47 (57.3%)
[16] array · 3 items
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[1]
4 (57.1%)
[2]
3 (42.9%)
[17] array · 2 items
[0]
T
[1]
P = 0.314
[18] array · 3 items
[0]
I
[1]
60 (56.1%)
[2]
47 (43.9%)
[19] array · 3 items
[0]
II
[1]
131 (46.5%)
[2]
151 (53.5%)
[20] array · 3 items
[0]
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[1]
38 (54.3%)
[2]
32 (45.7%)
[21] array · 3 items
[0]
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[1]
12 (52.2%)
[2]
11 (47.8%)
[22] array · 2 items
[0]
N
[1]
P = 0.001
[23] array · 3 items
[0]
-
[1]
171 (55.9%)
[2]
135 (44.1%)
[24] array · 3 items
[0]
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[1]
70 (39.8%)
[2]
106 (60.2%)
[25] array · 2 items
[0]
M
[1]
P = 0.036
[26] array · 3 items
[0]
-
[1]
188 (48.0%)
[2]
204 (52.0%)
[27] array · 3 items
[0]
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[1]
52 (60.5%)
[2]
34 (39.5%)
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Go analysis revealing biological processes centered on NDC80
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PMC7437940
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16
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NDC80 and MAD2L1 centered signaling pathways
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Table 6
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Go analysis revealing biological processes centered on NDC80
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[1]
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[3]
FDR
[4]
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[0]
Cell division
[1]
11
[2]
483
[3]
7.33E-16
[4]
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[0]
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[1]
10
[2]
253
[3]
7.33E-16
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AURKB,BUB1,BUB1B,CASC5,CENPE, MAD2L1,NDC80,NUF2,SPC25,ZWINT
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7
[2]
123
[3]
1.31E-11
[4]
AURKB,BUB1,BUB1B,CENPE,MAD2L1, NDC80,ZWINT
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Spindle attachment to kinetochore
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4
[2]
20
[3]
1.32E-08
[4]
AURKB,CASC5,CENPE,NDC80
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Spindle checkpoint
[1]
4
[2]
23
[3]
2.07E-08
[4]
AURKB,BUB1,BUB1B,MAD2L1
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section[16]/table-wrap[1]#Tab6
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Go analysis revealing biological processes centered on MAD2L1
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NDC80 and MAD2L1 centered signaling pathways
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Go analysis revealing biological processes centered on MAD2L1
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[2]
Background gene counts
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FDR
[4]
Matching proteins in the network
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[2]
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9
[2]
184
[3]
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[4]
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999
[3]
6.17E-08
[4]
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anaphase-promoting complex-dependent catabolic process
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[2]
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9.05E-15
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ANAPC1,ANAPC4,BUB1B,BUB3,CDC16,CDC20,MAD2L1
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Mitotic spindle assembly checkpoint
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5
[2]
21
[3]
4.46E-11
[4]
BUB1,BUB1B,BUB3,MAD1L1,MAD2L1
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And then multivariate COX regression analysis was performed using TCGA mRNA transcription data including 223 lung adenocarcinoma and 482 lung squamous cell carcinoma, which were downloaded from TCGA database [24] to identify the independent prognostic indicators from the univariate significant gene lists.
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And then multivariate COX regression analysis was performed using TCGA mRNA transcription data including 223 lung adenocarcinoma and 482 lung squamous cell carcinoma, which were downloaded from TCGA database [24] to identify the independent prognostic indicators from the univariate significant gene lists.
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32795325", "kind": "science-record", "revision": 7, "content_hash": "sha256:7bba95a0f90d1ee96f91a018d33bb4c7fcf607b78c73cb3738f8b1a6acec66c6", "created_at": "2026-11-01T15:41:07Z", "updated_at": "2026-11-01T22:02:02Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatic analysis revealing mitotic spindle assembly regulated NDC80 and MAD2L1 as prognostic biomarkers in non-small cell lung cancer development.", "doi": "10.1186/s12920-020-00762-5", "pmid": "32795325", "authors": ["Rong Wei", "Ziyue Wang", "Yaping Zhang", "Bin Wang", "Ningning Shen", "Li E", "Xin Li", "Lifang Shang", "Yangwei Shang", "Wenpeng Yan", "Xiaoqin Zhang", "Wenxia Ma", "Chen Wang"], "journal": "BMC medical genomics", "year": 2020, "abstract": "BACKGROUND: Lung cancer has been the leading cause of tumor related death, and 80% ~ 85% of it is non-small cell lung cancer (NSCLC). Even with the rising molecular targeted therapies, for example EGFR, ROS1 and ALK, the treatment is still challenging. The study is to identify credible responsible genes during the development of NSCLC using bioinformatic analysis, developing new prognostic biomarkers and potential gene targets to the disease.\nMETHODS: Firstly, three genes expression profiles GSE44077, GSE18842 and GSE33532 were picked from Gene Expression Omnibus (GEO) to analyze the genes with different expression level (GDEs) between NSCLC and normal lung samples, and the cellular location, molecular function and the biology pathways the GDEs enriched in were analyzed. Then, gene function modules of GDEs were explored based on the protein-protein interaction network (PPI), and the top module which contains most genes was identified, followed by containing genes annotation and survival analysis. Moreover, multivariate cox regression analysis was performed in addition to the Kaplan meier survival to narrow down the key genes scale. Further, the clinical pathological features of the picked key genes were explored using TCGA data.\nRESULTS: Three GEO profiles shared a total of 664 GDEs, including 232 up-regulated and 432 down-regulated genes. Based on the GDEs PPI network, the top function module containing a total of 69 genes was identified, and 31 of 69 genes were mitotic cell cycle regulation related. And survival analysis of the 31 genes revealed that 17/31 genes statistical significantly related to NSCLC overall survival, including 4 spindle assembly checkpoints, namely NDC80, BUB1B, MAD2L1 and AURKA. Further, multivariate cox regression analysis identified NDC80 and MAD2L1 as independent prognostic indicators in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) respectively. Interestingly, pearson correlation analysis indicated strong connection between the four genes NDC80, BUB1B, MAD2L1 and AURKA, and their clinical pathological features were addressed.\nCONCLUSIONS: Using bioinformatic analysis of GEO combined with TCGA data, we revealed two independent prognostic indicators in LUAD and LUSC respectively and analyzed their clinical features. 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