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pmid:33881940

APLN: A potential novel biomarker for cervical cancer.

Yusha Chen · Xiaoqian Lin · Jinwen Zheng · Jiancui Chen · Huifeng Xue · Xiangqin Zheng

Science progress · 2021 doi:10.1177/00368504211011341

Paper

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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
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pmid:33881940
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science-record
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2026-11-01T15:41:33Z
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2026-11-01T22:03:36Z
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paper object · 10 fields
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title
APLN: A potential novel biomarker for cervical cancer.
doi
10.1177/00368504211011341
pmid
33881940
authors array · 6 items
[0]
Yusha Chen
[1]
Xiaoqian Lin
[2]
Jinwen Zheng
[3]
Jiancui Chen
[4]
Huifeng Xue
[5]
Xiangqin Zheng
journal
Science progress
year
2021
abstract
Apelin (APLN) is recently demonstrated a direct association with many malignant diseases. However, its effects on cervical cancer remain unclear. This study therefore aims to evaluate the association between APLN expression and cervical cancer using publicly available data from The Cancer Genome Atlas (TCGA). The Pearson χ2 test and Fish exact test, as well as logistic regression, were used to evaluate the relationship between clinicopathological factors in cervical cancer and the expression of APLN. Additionally, the Cox regression and Kaplan-Meier methods were conducted to analyze the Overall Survival (OS) of cervical cancer patients in TCGA. Finally, gene set enrichment analysis (GSEA) was performed to establish its biological functions. High expression of APLN in cervical cancer was significantly associated with a more advanced clinical stage (OR = 1.91 (1.21-3.05) for Stage II, Stage III, and Stage IV vs Stage I, p = 0.006). Additionally, it was associated with poor outcome after primary therapy (OR = 2.14 (1.03-4.59) for Progressive Disease (PD), Stable Disease (SD), and Partial Response (PR) vs Complete Remission (CR), p = 0.045) and high histologic grade (OR = 1.67 (1.03-2.72) for G3 and G4 vs G1 and G2, p = 0.037). Moreover, multivariate analysis showed that high expression of APLN was associated with a shorter OS. GSEA demonstrated that six KEGG pathways, including PPAR signaling, ECM-receptor interaction, focal adhesion, MAPK signaling, TGF-beta signaling, and Gap junction pathways were differentially enriched in the high expression APLN phenotype. The recent study suggests that APLN plays an important role in the progression of cervical cancer and might be a promising prognostic biomarker of the disease.
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The expression levels of APLN in tumor and no-paired normal cervical tissue samples were compared using the Wilcoxon rank-sum test.
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sections[7] "Statistical analysis" paragraph 2
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The expression levels of APLN in tumor and no-paired normal cervical tissue samples were compared using the Wilcoxon rank-sum test.
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The RNA-seq data (Workflow Type: HTSeq-Counts) and corresponding clinical information were downloaded from the TCGA-Cervical Adenocarcinoma and Cervical Squamous Cell Carcinoma datasets.
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sections[3] "RNA-sequencing data preprocessing" paragraph 2
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The RNA-seq data (Workflow Type: HTSeq-Counts) and corresponding clinical information were downloaded from the TCGA-Cervical Adenocarcinoma and Cervical Squamous Cell Carcinoma datasets.
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The mtDNA Amerindian Haplogroup B2 enhances the risk for Cervical Cancer of HPV: de-regulation of mitochondrial genes may be involved.
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Gene expression in early stage cervical cancer
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Association between APLN expression and clinicopathological features in the TCGA cohort.
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Association between the expression of APLN and clinicopathologic features
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Table 1.
caption
Association between APLN expression and clinicopathological features in the TCGA cohort.
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[0] array · 5 items
[0]
Characters
[1]
Level
[2]
Low expression of APLN
[3]
High expression of APLN
[4]
p Value
[1] array · 5 items
[0]
n
[1]
[2]
152
[3]
152
[4]
[2] array · 5 items
[0]
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[1]
N0
[2]
75 (68.2%)
[3]
58 (69.9%)
[4]
0.924
[3] array · 3 items
[0]
N1
[1]
35 (31.8%)
[2]
25 (30.1%)
[4] array · 5 items
[0]
M stage (%)
[1]
M0
[2]
63 (96.9%)
[3]
53 (86.9%)
[4]
0.049a,b
[5] array · 3 items
[0]
M1
[1]
2 (3.1%)
[2]
8 (13.1%)
[6] array · 5 items
[0]
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[1]
Stage I
[2]
92 (62.6%)
[3]
70 (46.7%)
[4]
0.006 a
[7] array · 3 items
[0]
Stage II–IV
[1]
55 (37.4%)
[2]
80 (53.3%)
[8] array · 5 items
[0]
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[1]
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[2]
73 (48.0%)
[3]
49 (32.2%)
[4]
0.007 a
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[0]
Yes
[1]
79 (52.0%)
[2]
103 (67.8%)
[10] array · 5 items
[0]
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[1]
CR
[2]
99 (88.4%)
[3]
82 (78.1%)
[4]
0.129 b
[11] array · 3 items
[0]
PD
[1]
8 (7.1%)
[2]
14 (13.3%)
[12] array · 3 items
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PR
[1]
4 (3.6%)
[2]
4 (3.8%)
[13] array · 3 items
[0]
SD
[1]
1 (0.9%)
[2]
5 (4.8%)
[14] array · 5 items
[0]
Race (%)
[1]
Asian
[2]
15 (11.2%)
[3]
5 (4.0%)
[4]
0.054 b
[15] array · 3 items
[0]
Black or African American
[1]
12 (9.0%)
[2]
18 (14.4%)
[16] array · 3 items
[0]
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[1]
107 (79.9%)
[2]
102 (81.6%)
[17] array · 5 items
[0]
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[1]
Adenosquamous
[2]
29 (19.1%)
[3]
23 (15.1%)
[4]
0.446
[18] array · 3 items
[0]
Squamous cell carcinoma
[1]
123 (80.9%)
[2]
129 (84.9%)
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[0]
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[1]
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[2]
11 (7.7%)
[3]
7 (5.4%)
[4]
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G2
[1]
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[2]
57 (44.2%)
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[1]
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[2]
64 (49.6%)
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[1]
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[2]
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[2]
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[3]
10 (8.7%)
[4]
0.230
[24] array · 3 items
[0]
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[1]
45 (38.8%)
[2]
37 (32.2%)
[25] array · 3 items
[0]
Pre
[1]
56 (48.3%)
[2]
68 (59.1%)
[26] array · 5 items
[0]
PIK3CA status (%)
[1]
Mut
[2]
40 (27.8%)
[3]
42 (29.6%)
[4]
0.837
[27] array · 3 items
[0]
WT
[1]
104 (72.2%)
[2]
100 (70.4%)
[28] array · 5 items
[0]
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[1]
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[2]
91 (59.9%)
[3]
95 (62.5%)
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0.724
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[0]
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[1]
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APLN expression a associated with clinical pathological characteristic (logistic regression).
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Association between the expression of APLN and clinicopathologic features
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Table 2.
caption
APLN expression a associated with clinical pathological characteristic (logistic regression).
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[0] array · 4 items
[0]
Characteristics
[1]
Odds ratio in APLN expression
[2]
Odds ratio (OR)
[3]
p Value
[1] array · 4 items
[0]
N stage (N1 vs N0)
[1]
193
[2]
0.92 (0.50–1.71)
[3]
0.801
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M stage (M1 vs M0)
[1]
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[2]
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[3]
0.055
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[1]
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[2]
1.91 (1.21–3.05)
[3]
0.006 b
[4] array · 4 items
[0]
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[1]
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[2]
1.32 (0.73–2.43)
[3]
0.362
[5] array · 4 items
[0]
Histologic grade (G3 and G4 vs G1 and G2)
[1]
272
[2]
1.67 (1.03–2.72)
[3]
0.037 b
[6] array · 4 items
[0]
PIK3CA status (Mut vs WT)
[1]
286
[2]
1.09 (0.65–1.83)
[3]
0.737
[7] array · 4 items
[0]
Primary therapy outcome (PD, SD, and PR vs CR)
[1]
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[2]
2.14 (1.03–4.59)
[3]
0.045 b
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Univariate and multivariate Cox proportional hazard analysis of APLN expression and OS for patients with cervical cancer in the TCGA cohort.
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Univariate and multivariate Cox analyses of survival
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Table 3.
caption
Univariate and multivariate Cox proportional hazard analysis of APLN expression and OS for patients with cervical cancer in the TCGA cohort.
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[0] array · 6 items
[0]
Characteristics
[1]
Total (N)
[2]
HR (95% CI) univariate analysis
[3]
p Value univariate analysis
[4]
HR (95% CI) multivariate analysis
[5]
p Value multivariate analysis
[1] array · 6 items
[0]
N stage (N1 vs N0)
[1]
193
[2]
2.695 (1.358–5.349)
[3]
0.005 a
[4]
2.887 (1.206–6.912)
[5]
0.017 a
[2] array · 6 items
[0]
Clinical stage (stage II and stage III and stage IV vs stage I)
[1]
297
[2]
1.429 (0.896–2.280)
[3]
0.134
[4]
[5]
[3] array · 6 items
[0]
Radiation therapy (yes vs no)
[1]
304
[2]
1.153 (0.681–1.951)
[3]
0.596
[4]
[5]
[4] array · 6 items
[0]
Histological type (squamous vs adenosquamous cell carcinoma)
[1]
304
[2]
1.010 (0.530–1.926)
[3]
0.976
[4]
[5]
[5] array · 6 items
[0]
Menopause status (post vs pre and peri)
[1]
231
[2]
1.275 (0.744–2.185)
[3]
0.376
[4]
[5]
[6] array · 6 items
[0]
Histologic grade (G3 and G4 vs G1 and G2)
[1]
272
[2]
0.889 (0.527–1.502)
[3]
0.661
[4]
[5]
[7] array · 6 items
[0]
Age (>50 vs ≤50)
[1]
304
[2]
1.317 (0.825–2.101)
[3]
0.248
[4]
[5]
[8] array · 6 items
[0]
PIK3CA status (Mut vs WT)
[1]
286
[2]
1.011 (0.599–1.707)
[3]
0.967
[4]
[5]
[9] array · 6 items
[0]
Primary therapy outcome (PD, SD, and PR vs CR)
[1]
217
[2]
13.514 (7.250–25.189)
[3]
<0.001 a
[4]
7.877 (2.792–22.222)
[5]
<0.001 a
[10] array · 6 items
[0]
Race (Asian and Black or African American vs White)
[1]
259
[2]
0.841 (0.427–1.658)
[3]
0.618
[4]
[5]
[11] array · 6 items
[0]
APLN (high vs low)
[1]
304
[2]
1.942 (1.192–3.164)
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Univariate and multivariate Cox proportional hazard analysis of APLN expression and PFS for patients with cervical cancer in the TCGA cohort.
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PMC10454995
section_index
11
section_title
Univariate and multivariate Cox analyses of survival
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table object · 8 fields
label
Table 4.
caption
Univariate and multivariate Cox proportional hazard analysis of APLN expression and PFS for patients with cervical cancer in the TCGA cohort.
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[0] array · 6 items
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[1]
Total (N)
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HR (95% CI) univariate analysis
[3]
p Value univariate analysis
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HR (95% CI) multivariate analysis
[5]
p Value multivariate analysis
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N stage (N1 vs N0)
[1]
193
[2]
1.983 (0.986–3.990)
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0.055
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Clinical stage (stage II, stage III and stage IV vs stage I)
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[2]
1.308 (0.821–2.084)
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0.258
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[3] array · 6 items
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Radiation therapy (yes vs no)
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1.288 (0.754–2.200)
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0.354
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Histological type (squamous vs adenosquamous cell carcinoma)
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304
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0.778 (0.433–1.397)
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0.749
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Histologic grade (G3 and G4 vs G1 and G2)
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[2]
1.594 (0.967–2.627)
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[0]
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304
[2]
1.612 (1.012–2.568)
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0.044 a
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1.174 (0.688–2.002)
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0.557
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PIK3CA status (Mut vs WT)
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[2]
0.994 (0.589–1.679)
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0.983
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[5]
[9] array · 6 items
[0]
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[2]
7.907 (4.631–13.500)
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<0.001 a
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<0.001 a
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[2]
1.066 (0.553–2.057)
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0.848
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APLN (high vs low)
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0.032 a
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Univariate and multivariate Cox proportional hazard analysis of APLN expression and DSS for patients with cervical cancer in the TCGA cohort.
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pmcid
PMC10454995
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11
section_title
Univariate and multivariate Cox analyses of survival
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Table 5.
caption
Univariate and multivariate Cox proportional hazard analysis of APLN expression and DSS for patients with cervical cancer in the TCGA cohort.
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[0]
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Total (N)
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HR (95% CI) univariate analysis
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p Value univariate analysis
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HR (95% CI) multivariate analysis
[5]
p Value multivariate analysis
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N stage (N1 vs N0)
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191
[2]
3.303 (1.446–7.541)
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0.005 a
[4]
2.970 (1.187–7.430)
[5]
0.02 a
[2] array · 6 items
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[2]
1.608 (0.941–2.749)
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0.082
[4]
[5]
[3] array · 6 items
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Radiation therapy (yes vs no)
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[2]
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Menopause status (post vs pre and peri)
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1.233 (0.678–2.243)
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0.955 (0.530–1.720)
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0.877
[4]
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[2]
1.333 (0.780–2.278)
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PIK3CA status (Mut vs WT)
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[2]
1.097 (0.606–1.989)
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0.759
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[9] array · 6 items
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[2]
16.934 (8.629–33.235)
[3]
<0.001 a
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10.497 (3.470–31.753)
[5]
<0.001 a
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[2]
0.770 (0.344–1.724)
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0.526
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APLN (high vs low)
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[2]
2.178 (1.236–3.838)
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0.007 a
[4]
5.134 (1.854–14.216)
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KEGG pathways enriched in the high APLN expression group using GSEA.
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APLN-related signaling pathways based on gene set enrichment analysis (GSEA)
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Table 6.
caption
KEGG pathways enriched in the high APLN expression group using GSEA.
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[0]
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p. adjust
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section[12]/table-wrap[1]#table6-00368504211011341
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The expression levels of APLN in tumor and no-paired normal cervical tissue samples were compared using the Wilcoxon rank-sum test.
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GSE29570
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The RNA-seq data (Workflow Type: HTSeq-Counts) and corresponding clinical information were downloaded from the TCGA-Cervical Adenocarcinoma and Cervical Squamous Cell Carcinoma datasets.
basis
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The expression levels of APLN in tumor and no-paired normal cervical tissue samples were compared using the Wilcoxon rank-sum test.
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33881940", "kind": "science-record", "revision": 8, "content_hash": "sha256:30ccdace1b843f75b13128a4488210bbecebdadef15ad805fb41f62eede34350", "created_at": "2026-11-01T15:41:33Z", "updated_at": "2026-11-01T22:03:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "APLN: A potential novel biomarker for cervical cancer.", "doi": "10.1177/00368504211011341", "pmid": "33881940", "authors": ["Yusha Chen", "Xiaoqian Lin", "Jinwen Zheng", "Jiancui Chen", "Huifeng Xue", "Xiangqin Zheng"], "journal": "Science progress", "year": 2021, "abstract": "Apelin (APLN) is recently demonstrated a direct association with many malignant diseases. However, its effects on cervical cancer remain unclear. This study therefore aims to evaluate the association between APLN expression and cervical cancer using publicly available data from The Cancer Genome Atlas (TCGA). The Pearson χ2 test and Fish exact test, as well as logistic regression, were used to evaluate the relationship between clinicopathological factors in cervical cancer and the expression of APLN. Additionally, the Cox regression and Kaplan-Meier methods were conducted to analyze the Overall Survival (OS) of cervical cancer patients in TCGA. Finally, gene set enrichment analysis (GSEA) was performed to establish its biological functions. High expression of APLN in cervical cancer was significantly associated with a more advanced clinical stage (OR = 1.91 (1.21-3.05) for Stage II, Stage III, and Stage IV vs Stage I, p = 0.006). Additionally, it was associated with poor outcome after primary therapy (OR = 2.14 (1.03-4.59) for Progressive Disease (PD), Stable Disease (SD), and Partial Response (PR) vs Complete Remission (CR), p = 0.045) and high histologic grade (OR = 1.67 (1.03-2.72) for G3 and G4 vs G1 and G2, p = 0.037). Moreover, multivariate analysis showed that high expression of APLN was associated with a shorter OS. GSEA demonstrated that six KEGG pathways, including PPAR signaling, ECM-receptor interaction, focal adhesion, MAPK signaling, TGF-beta signaling, and Gap junction pathways were differentially enriched in the high expression APLN phenotype. 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