Flowchart of the study. CC, cervical cancer; EC, endometrial cancer; VC, vulvar cancer, PPI, protein-protein interaction.
DEGs in CC, EC and VC. (A) Venn diagram of three gynecological tumor types. The yellow circles represent the DEGs in CC, the blue circles represent the DEGs in EC and the red circles represent the DEGs in VC. The overlapping areas indicate the shared genes of any two or three groups. (B) The protein-protein interaction network of the 25 hub genes. The circle nodes represent genes. Red indicates genes in CC, yellow represents genes in EC and green indicates genes in VC. The thickness of the line between any two nodes represents the strength of the connection. (C) Gene ontology analysis of 25 DEGs. The results are presented for the following three categories: Biological process, cellular component and molecular function DEG, differentially expressed gene; CC, cervical cancer; EC, endometrial cancer; VC, vulvar cancer.
Pathway networks. (A) Model of the pathway network. The red circle nodes indicate a pathway and the lines represent the interactions between two pathways. The strength of the interaction is represented by the thickness of the line, according to the mean value of JC and OC. (B) Model of the core pathway network. Red circle nodes indicate a pathway and the lines represent the interactions between two pathways The strength of the interaction is represented by the thickness of the line according to the mean value of JC and OC. JC, Jaccard coefficient; OC, overlap coefficient.
Gene-Pathway network. Orange diamonds indicate a pathway and circles represent a gene. Red indicates genes in cervical cancer, yellow represents genes in endometrial cancer and green indicates genes in vulvar cancer.
Sub-molecular network of CC, EC and VC. Orange diamonds indicate a pathway and circles represent a gene. Red indicates genes in CC, yellow represent genes in EC and green indicates genes in VC. CC, cervical cancer; EC, endometrial cancer; VC, vulvar cancer.
Topological parameters of the hub genes.
| Gene | Degree | Betweeness | Closeness | Group | Regulation |
|---|---|---|---|---|---|
| Mean | 13 | 2081.81034 | 3.73×10−4 | – | – |
| CDK1 | 115 | 20448.4838 | 5.21×10−4 | CC/EC | Up |
| CCNB1 | 100 | 16335.9142 | 5.23×10−4 | CC/EC | Up |
| CDC20 | 92 | 8148.54809 | 4.76×10−4 | EC | Up |
| CCNA2 | 91 | 8126.90458 | 4.89×10−4 | CC/EC/VC | Up |
| AURKA | 90 | 9181.94344 | 4.76×10−4 | EC/VC | Up |
| TOP2A | 87 | 21409.6376 | 5.15×10−4 | EC/VC | Up |
| UBE2C | 82 | 14916.6491 | 4.82×10−4 | EC/VC | Up |
| BIRC5 | 80 | 16279.0157 | 5.13×10−4 | EC/VC | Up |
| PCNA | 62 | 26080.2036 | 5.25×10−4 | CC/EC | Up |
| VEGFA | 56 | 32712.0335 | 5.43×10−4 | VC | Up |
| PIK3R1 | 46 | 24576.8505 | 4.91×10−4 | VC | Down |
| HIST1H2BK | 43 | 8689.20717 | 4.70×10−4 | CC/VC | Up |
| HIST1H2BD | 43 | 8689.20717 | 4.70×10−4 | VC | Up |
| HIST1H2BH | 42 | 8291.98846 | 4.70×10−4 | VC | Up |
| ACACB | 41 | 40853.547 | 4.98×10−4 | VC | Down |
| CXCL8 | 40 | 28927.396 | 5.16×10−4 | VC | Up |
| H2AFZ | 39 | 8793.56814 | 4.67×10−4 | CC | Up |
| IGF1 | 38 | 16278.2011 | 5.07×10−4 | CC/VC | Down |
| ACLY | 37 | 34157.4527 | 4.81×10−4 | EC | Up |
| CCND1 | 36 | 28548.907 | 5.39×10−4 | EC | Up |
| GAPDH | 33 | 41598.1258 | 5.39×10−4 | EC | Up |
| PPP2R5C | 32 | 10238.8057 | 4.75×10−4 | CC | UP |
| FYN | 32 | 17254.3572 | 5.22×10−4 | CC/VC | Down |
| FGF2 | 32 | 19465.3169 | 5.20×10−4 | EC | Down |
| BCL2 | 32 | 17923.6004 | 4.86×10−4 | VC | Down |
CC, cervical cancer; EC, endometrial cancer; VC, vulvar cancer.
Pathways enriched in three types of gynecological cancer.
| Pathway | Regulation | P-value | Genes in the pathway |
|---|---|---|---|
| Viral carcinogenesis | – | 3.43×10−9 | HIST1H2BD, CCND1, CDK1, HIST1H2BH, CDC20, PIK3R1, HIST1H2BK, CCNA2 |
| Hepatitis B | – | 9.66×10−9 | BIRC5, CCND1, BCL2, PIK3R1, PCNA, CXCL8, CCNA2 |
| AMPK signaling pathway | – | 1.13×10−7 | CCND1, PPP2R5C, IGF1, ACACB, PIK3R1, CCNA2 |
| Oocyte meiosis | – | 1.31×10−7 | AURKA, PPP2R5C, IGF1, CDK1, CDC20, CCNB1 |
| Cell cycle | Up | 1.31×10−7 | CCND1, CDK1, CDC20, PCNA, CCNA2, CCNB1 |
| EGFR tyrosine kinase inhibitor resistance | – | 4.35×10−7 | FGF2, BCL2, IGF1, PIK3R1, VEGFA |
| Pathways in cancer | – | 6.44×10−7 | FGF2, BIRC5, CCND1, BCL2, IGF1, PIK3R1, CXCL8, VEGFA |
| Progesterone-mediated oocyte maturation | – | 1.15×10−6 | IGF1, CDK1, PIK3R1, CCNA2, CCNB1 |
| AGE-RAGE signaling pathway in diabetic complications | – | 1.35×10−6 | CCND1, BCL2, PIK3R1, CXCL8, VEGFA |
| HIF-1 signaling pathway | – | 1.49×10−6 | BCL2, IGF1, GAPDH, PIK3R1, VEGFA |
| Focal adhesion | – | 2.13×10−6 | CCND1, BCL2, IGF1, FYN, PIK3R1, VEGFA |
| PI3K-Akt signaling pathway | – | 3.48×10−6 | FGF2, CCND1, BCL2, PPP2R5C, IGF1, PIK3R1, VEGFA |
| p53 Signaling Pathway | – | 3.94×10−6 | CCND1, BCL2, PCNA |
| IL-7 Signal Transduction | Down | 4.77×10−6 | BCL2, FYN, PIK3R1 |
| Colorectal cancer | – | 5.72×10−6 | BIRC5, CCND1, BCL2, PIK3R1 |
| p53 signaling pathway | – | 1.00×10−5 | CCND1, IGF1, CDK1, CCNB1 |
| Melanoma | – | 1.00×10−5 | FGF2, CCND1, IGF1, PIK3R1 |
| Cyclins and Cell Cycle Regulation | Up | 1.23×10−5 | CCND1, CDK1, CCNB1 |
| Platinum drug resistance | – | 1.25×10−5 | BIRC5, BCL2, PIK3R1, TOP2A |
| Regulation of BAD phosphorylation | Down | 1.80×10−5 | BCL2, IGF1, PIK3R1 |
| Prostate cancer | – | 2.52×10−5 | CCND1, BCL2, IGF1, PIK3R1 |
| Endocrine resistance | – | 3.71×10−5 | CCND1, BCL2, IGF1, PIK3R1 |
| Proteoglycans in cancer | – | 4.47×10−5 | FGF2, CCND1, IGF1, PIK3R1, VEGFA |
| Bladder cancer | Up | 7.25×10−5 | CCND1, CXCL8, VEGFA |
| Sphingolipid signaling pathway | – | 8.32×10−5 | BCL2, PPP2R5C, FYN, PIK3R1 |
| FoxO signaling pathway | – | 1.29×10−4 | CCND1, IGF1, PIK3R1, CCNB1 |
| Systemic lupus erythematosus | Up | 1.32×10−4 | H2AFZ, HIST1H2BD, HIST1H2BH, HIST1H2BK |
| NFAT and Hypertrophy of the heart (Transcription in the broken heart) | Down | 1.66×10−4 | FGF2, IGF1, PIK3R1 |
| Breast cancer | – | 1.80×10−4 | FGF2, CCND1, IGF1, PIK3R1 |
| Activation of Src by Protein-tyrosine phosphatase alpha | Up | 2.11×10−4 | CDK1, CCNB1 |
| Sonic Hedgehog (SHH) Receptor Ptc1 Regulates cell cycle | Up | 2.11×10−4 | CDK1, CCNB1 |
| AKAP95 role in mitosis and chromosome dynamics | Up | 2.52×10−4 | CDK1, CCNB1 |
| Glioma | – | 2.75×10−4 | CCND1, IGF1, PIK3R1 |
| Pancreatic cancer | – | 2.75×10−4 | CCND1, PIK3R1, VEGFA |
| Expression of cyclins regulates progression through the cell cycle by activating cyclin-dependent kinases. | Up | 2.98×10−4 | CCND1, CCNA2 |
| The IGF-1 Receptor and Longevity | Down | 4.00×10−4 | IGF1, PIK3R1 |
| Alcoholism | Up | 4.22×10−4 | H2AFZ, HIST1H2BD, HIST1H2BH, HIST1H2BK |
| B Cell Survival Pathway | – | 4.57×10−4 | BIRC5, PIK3R1 |
| Small cell lung cancer | – | 6.12×10−4 | CCND1, BCL2, PIK3R1 |
| Stathmin and breast cancer resistance to antimicrotubule agents | Up | 6.48×10−4 | CDK1, CCNB1 |
| Epstein-Barr virus infection | – | 6.64×10−4 | BCL2, CDK1, PIK3R1, CCNA2 |
| Skeletal muscle hypertrophy is regulated via AKT/mTOR pathway | Down | 7.19×10−4 | IGF1, PIK3R1 |
| Rap1 signaling pathway | – | 7.54×10−4 | FGF2, IGF1, PIK3R1, VEGFA |
| IGF-1 Signaling Pathway | Down | 7.94×10−4 | IGF1, PIK3R1 |
| Ras signaling pathway | – | 1.01×10−3 | FGF2, IGF1, PIK3R1, VEGFA |
| Erk and PI-3 Kinase Are Necessary for Collagen Binding in Corneal Epithelia | Down | 1.04×10−3 | FYN, PIK3R1 |
| Cell Cycle: G2/M Checkpoint | Up | 1.04×10−3 | CDK1, CCNB1 |
| Influence of Ras and Rho proteins on G1 to S Transition | – | 1.22×10−3 | CCND1, PIK3R1 |
| Genes related to IL4 rceptor signaling in B lymphocytes | Down | 1.32×10−3 | BCL2, PIK3R1 |
| Inactivation of Gsk3 by AKT causes accumulation of b-catenin in Alveolar Macrophages | Up | 1.32×10−3 | CCND1, PIK3R1 |
| Cholinergic synapse | Down | 1.41×10−3 | BCL2, FYN, PIK3R1 |
| Cell Cycle: G1/S Check Point | Up | 1.42×10−3 | CCND1, CDK1 |
| VEGF, Hypoxia, and Angiogenesis | – | 1.52×10−3 | PIK3R1, VEGFA |
| HTLV–I infection | – | 1.57×10−3 | CCND1, CDC20, PIK3R1, PCNA |
| Control of skeletal myogenesis by HDAC and calcium/calmodulin-dependent kinase (CaMK) | Down | 1.63×10−3 | IGF1, PIK3R1 |
| Apoptosis-multiple species | – | 1.97×10−3 | BIRC5, BCL2 |
| How Progesterone Initiates Oocyte Membrane | Up | 2.09×10−3 | CDK1, CCNB1 |
| Measles | – | 2.36×10−3 | CCND1, FYN, PIK3R1 |
| Aldosterone-regulated sodium reabsorption | Down | 2.47×10−3 | IGF1, PIK3R1 |
| Apoptosis | – | 2.56×10−3 | BIRC5, BCL2, PIK3R1 |
| IL-2 Receptor Beta Chain in T cell Activation | Down | 2.60×10−3 | BCL2, PIK3R1 |
| Signaling pathways regulating pluripotency of stem cells | Down | 2.62×10−3 | FGF2, IGF1, PIK3R1 |
| Fluid shear stress and atherosclerosis | – | 2.78×10−3 | BCL2, PIK3R1, VEGFA |
| Phospholipase D signaling pathway | – | 3.01×10−3 | FYN, PIK3R1, CXCL8 |
| Jak-STAT signaling pathway | – | 3.63×10−3 | CCND1, BCL2, PIK3R1 |
| Members of the BCR signaling pathway | Down | 3.80×10−3 | BCL2, PIK3R1 |
| Hedgehog signaling pathway | – | 3.96×10−3 | CCND1, BCL2 |
| T Cell Receptor Signaling Pathway | Down | 3.96×10−3 | FYN, PIK3R1 |
| Endometrial cancer | – | 4.47×10−3 | CCND1, PIK3R1 |
| Genes encoding secreted soluble factors | – | 4.58×10−3 | FGF2, IGF1, CXCL8, VEGFA |
| Acute myeloid leukemia | – | 5.39×10−3 | CCND1, PIK3R1 |
| Non-small cell lung cancer | – | 5.97×10−3 | CCND1, PIK3R1 |
| VEGF signaling pathway | – | 6.18×10−3 | PIK3R1, VEGFA |
| Viral myocarditis | – | 6.18×10−3 | CCND1, FYN |
| Longevity regulating pathway-multiple species | Down | 6.80×10−3 | IGF1, PIK3R1 |
| Renal cell carcinoma | – | 7.45×10−3 | PIK3R1, VEGFA |
| Fc epsilon RI signaling pathway | – | 8.13×10−3 | FYN, PIK3R1 |
| Prolactin signaling pathway | – | 8.60×10−3 | CCND1, PIK3R1 |
| Chronic myeloid leukemia | – | 8.84×10−3 | CCND1, PIK3R1 |
| Longevity regulating pathway | – | 1.36×10−2 | IGF1, PIK3R1 |
| Genes related to Wnt-mediated signal transduction | Up | 1.36×10−2 | CCND1, GAPDH |
| Rheumatoid arthritis | Up | 1.39×10−2 | CXCL8, VEGFA |
| NF-kappa B signaling pathway | – | 1.54×10−2 | BCL2, CXCL8 |
| Amoebiasis | – | 1.57×10−2 | PIK3R1, CXCL8 |
| Cdc25 activates the cdc2/cyclin B complex to induce the G2/M transition. | Up | 1.60×10−2 | CDK1 |
| Inflammatory mediator regulation of TRP channels | Down | 1.60×10−2 | IGF1, PIK3R1 |