Table 3.
Pathway analysis results for the prostate cancer (PCa) dataset (adjusted p < 0.05).
| ID | Pathway | % CGC genes | pathfindR | DAVID | SPIA | GSEA | GSEAPreranked | Brief Description |
|---|---|---|---|---|---|---|---|---|
| hsa04392 | Hippo signaling pathway - multiple species | 17.24 | <0.001 | – | – | – | – | The hippo pathway effector YAP regulates motility, invasion, and castration-resistant growth of prostate cancer cells (Zhang et al., 2015). |
| hsa03010 | Ribosome | 1.96 | <0.001 | – | – | 0.425191 | 1 | Certain ribosomal proteins are altered and may serve as putative biomarkers for prostate cancer (Arthurs et al., 2017). |
| hsa04012 | ErbB signaling pathway | 40 | <0.001 | – | 0.637063484 | – | – | There are interactions among the ErbB receptor network, its downstream pathways, and androgen receptor signaling (El Sheikh et al., 2003). |
| hsa04625 | C-type lectin receptor signaling pathway | 27.88 | <0.001 | – | – | – | – | C-type lectin receptors are emerging orchestrators of sterile inflammation and represent potential therapeutic targets in many cancers, including PCa (Chiffoleau, 2018). C-type lectins were shown to facilitate tumor metastasis (Ding et al., 2017). |
| hsa04010 | MAPK signaling pathway | 17.97 | <0.001 | – | 0.282733912 | – | 0.90003437 | MAPK signaling pathways act through their effects on apoptosis, survival, metastatic potential, and androgen-independent growth in prostate cancer (Rodríguez-Berriguete et al., 2012). |
| hsa05205 | Proteoglycans in cancer | 27.86 | <0.001 | 0.02399376 | – | – | – | Proteoglycans play roles in modulating cancer progression, invasion and metastasis (Iozzo and Sanderson, 2011). |
| hsa04919 | Thyroid hormone signaling pathway | 32.76 | <0.001 | 0.5109672 | – | – | – | |
| hsa04390 | Hippo signaling pathway | 16.23 | <0.001 | 0.10679672 | – | – | – | The hippo pathway effector YAP regulates motility, invasion, and castration-resistant growth of prostate cancer cells (Zhang et al., 2015). |
| hsa04728 | Dopaminergic synapse | 11.45 | <0.001 | 0.06897641 | 0.034643839 | – | – | |
| hsa04270 | Vascular smooth muscle contraction | 12.4 | <0.001 | <0.001 | <0.001 | – | 0.9954409 | |
| hsa04810 | Regulation of actin cytoskeleton | 15.02 | <0.001 | 0.02727598 | 0.033699531 | – | – | Dysregulated in cancer cell migration and invasion (Yamaguchi and Condeelis, 2007). |
| hsa04218 | Cellular senescence | 25.63 | <0.001 | – | – | – | – | Cellular senescence may play a role in treatment resistance in PCa (Blute et al., 2017). |
| hsa04520 | Adherens junction | 31.94 | <0.001 | – | – | – | – | Dysregulation of the adherens junction system has particular implications in transformation and tumor invasion (Knights et al., 2012). |
| hsa04962 | Vasopressin-regulated water reabsorption | 13.64 | <0.001 | – | 0.655412336 | – | – | |
| hsa04310 | Wnt signaling pathway | 17.72 | <0.001 | 0.14714863 | 0.174150166 | – | – | Wnt signaling is implicated in PCa biology (Murillo-Garzon and Kypta, 2017). |
| hsa04151 | PI3K-Akt signaling pathway | 21.47 | <0.001 | – | – | – | – | Activation of PI3K-Akt signaling pathway promotes prostate cancer cell invasion (Shukla et al., 2007). |
| hsa04921 | Oxytocin signaling pathway | 13.16 | <0.001 | 0.09939094 | – | – | – | Oxytocin signaling has a role in prostate cancer metastasis (Zhong et al., 2010). |
| hsa04144 | Endocytosis | 11.48 | <0.001 | 0.14183304 | – | – | – | Defective vesicular trafficking of growth factor receptors, as well as unbalanced recycling of integrin- and cadherin-based adhesion complexes, has emerged as a multifaceted hallmark of malignant cells (Mosesson et al., 2008). |
| hsa04928 | Parathyroid hormone synthesis, secretion and action | 20.75 | <0.001 | – | – | – | – | |
| hsa04931 | Insulin resistance | 14.81 | <0.001 | 0.44248049 | – | – | – | Men in the highest tertile of insulin resistance (IR) had an increased risk of prostate cancer, indicating a potential pathogenetic link of IR with prostate cancer (Hsing et al., 2003). |
| hsa05170 | Human immunodeficiency virus 1 infection | 16.98 | <0.001 | – | – | – | – | |
| hsa04071 | Sphingolipid signaling pathway | 18.64 | <0.001 | – | – | – | – | Sphingolipids are modulators of cancer cell death and represent potential therapeutic targets (Segui et al., 2006; Shaw et al., 2018). |
| hsa04510 | Focal adhesion | 19.1 | <0.001 | 0.01182864 | 0.003797795 | – | – | Cancer cells exhibit highly altered focal adhesion dynamics (Maziveyi and Alahari, 2017). |
| hsa04014 | Ras signaling pathway | 18.1 | <0.001 | – | – | – | – | Ras signaling plays an important role in prostate cancer progression and is a possibly mediator of hormone resistance (Weber and Gioeli, 2004; Whitaker and Neal, 2010). |
| hsa04140 | Autophagy - animal | 17.19 | <0.001 | – | 0.91466497 | 0.7367432 | – | Autophagy is a modulator of PCa biology and is a therapeutic target (Farrow et al., 2014). |
| hsa04360 | Axon guidance | 14.36 | <0.001 | 0.36615434 | 0.174150166 | – | – | |
| hsa04910 | Insulin signaling pathway | 18.98 | <0.001 | – | 0.592610905 | – | – | Insulin signaling has crucial roles in cell proliferation and death. Insulin receptors were detected on primary human prostate cancers (Cox et al., 2009; Bertuzzi et al., 2016). |
| hsa05132 | Salmonella infection | 8.14 | 0.001024926 | – | 0.884388639 | – | – | |
| hsa04261 | Adrenergic signaling in cardiomyocytes | 11.81 | 0.001251519 | 0.1359051 | – | – | – | |
| hsa05213 | Endometrial cancer | 60.34 | 0.001571998 | – | 0.889535144 | 0.9776995 | 0.9350631 | |
| hsa05211 | Renal cell carcinoma | 44.93 | 0.001704596 | – | 0.958690885 | – | – | |
| hsa05200 | Pathways in cancer | 26.81 | 0.001864931 | 0.44205232 | 0.592610905 | – | – | “Meta”-pathway of cancer pathways. |
| hsa05214 | Glioma | 44 | 0.00191144 | – | 0.678606672 | – | – | |
| hsa04110 | Cell cycle | 23.39 | 0.00200072 | – | 0.53576482 | 0.73860705 | – | Dysregulation of the cell cycle is implicated in the biology of many cancers, including PCa (Hartwell and Kastan, 1994; Collins et al., 1997; Balk and Knudsen, 2008). |
| hsa05410 | Hypertrophic cardiomyopathy (HCM) | 6.02 | 0.002088682 | 0.01508581 | – | – | 0.94539815 | |
| hsa05202 | Transcriptional misregulation in cancer | 44.09 | 0.002227785 | – | 0.909985754 | – | – | Core cancer pathway. |
| hsa04068 | FoxO signaling pathway | 29.55 | 0.00256445 | – | – | – | – | FOXO signaling is implicated and considered as a therapeutic target in many cancers, including PCa (Farhan et al., 2017). |
| hsa04620 | Toll-like receptor signaling pathway | 14.42 | 0.002757387 | – | 0.999737262 | 1 | – | TLRs may serve as a double-edged sword in prostate cancer tumorigenesis by promoting malignant transformation of epithelial cells and tumor growth, or on the contrary, inducing apoptosis, and inhibiting tumor progression (Zhao et al., 2014). |
| hsa05414 | Dilated cardiomyopathy (DCM) | 8.89 | 0.002884316 | 0.00445895 | 0.00145624 | – | 0.9310661 | |
| hsa05224 | Breast cancer | 31.29 | 0.002996465 | – | – | – | – | |
| hsa04340 | Hedgehog signaling pathway | 21.28 | 0.003701704 | – | 0.603911642 | – | – | Hedgehog signaling plays an important role in the development and progression of PCa (Gonnissen et al., 2013). |
| hsa05215 | Prostate cancer | 51.55 | 0.004678127 | – | 0.637063484 | – | – | The pathway of the disease. |
| hsa04211 | Longevity regulating pathway | 25.84 | 0.004704898 | – | – | – | – | |
| hsa04022 | cGMP-PKG signaling pathway | 11.04 | 0.004947514 | 0.00142051 | – | – | – | cGMP-PKG signaling inhibits cell proliferation and induces apoptosis (Fajardo et al., 2014). |
| hsa05032 | Morphine addiction | 4.4 | 0.005138281 | 0.37736294 | 0.174150166 | – | – | |
| hsa04550 | Signaling pathways regulating pluripotency of stem cells | 31.65 | 0.00540706 | – | – | – | – | |
| hsa04912 | GnRH signaling pathway | 19.35 | 0.005600378 | 0.37736294 | 0.340227111 | – | 0.9284794 | GnRH signaling has roles in cancer cell proliferation and metastasis in many cancers, including PCa (Gründker and Emons, 2017). |
| hsa05165 | Human papillomavirus infection | 19.09 | 0.005787239 | – | – | – | – | HPV infection is associated with increasing risk of PCa, indicating a potential pathogenetic link between HPV and prostate cancer (Yin et al., 2017). |
| hsa05012 | Parkinson disease | 6.34 | 0.005882045 | – | 0.895565575 | – | – | |
| hsa04070 | Phosphatidylinositol signaling system | 6.06 | 0.007170858 | 0.47255633 | 0.592215095 | – | – | Deregulation PI3 kinase signaling is implicated in prostate carcinogenesis (Elfiky and Jiang, 2013). |
| hsa04750 | Inflammatory mediator regulation of TRP channels | 10.1 | 0.007170858 | 0.47255633 | – | – | – | TRP channels have emerged as key proteins in central mechanisms of the carcinogenesis such as cell proliferation, apoptosis and migration (Gkika and Prevarskaya, 2011). |
| hsa04933 | AGE-RAGE signaling pathway in diabetic complications | 31 | 0.007170858 | – | – | – | – | |
| hsa05231 | Choline metabolism in cancer | 27.27 | 0.007170858 | – | – | – | – | Core cancer pathway. Choline metabolites can be used as potential prognostic biomarkers for the management of prostate cancer patients (Awwad et al., 2012). |
| hsa04730 | Long-term depression | 23.33 | 0.007411265 | 0.29433246 | 0.228920589 | – | – | |
| hsa04152 | AMPK signaling pathway | 15.83 | 0.007412407 | – | – | – | – | First identified as a master regulator of metabolism, AMPK may have numerous roles beyond metabolism. AMPK signaling can have context-dependent effects in prostate cancer (Khan and Frigo, 2017). |
| hsa05210 | Colorectal cancer | 51.16 | 0.007572536 | – | 0.53576482 | – | 0.8859366 | |
| hsa04660 | T cell receptor signaling pathway | 31.68 | 0.007759806 | – | 0.999737262 | – | – | T-cell receptor signaling modulates control of anti-cancer immunity (Cronin and Penninger, 2007). |
| hsa04916 | Melanogenesis | 20.79 | 0.007759806 | 0.23117007 | 0.191012563 | – | – | |
| hsa04922 | Glucagon signaling pathway | 11.65 | 0.008383558 | – | – | – | – | |
| hsa04971 | Gastric acid secretion | 8 | 0.008625239 | 0.17201492 | 0.174150166 | – | – | |
| hsa05164 | Influenza A | 15.79 | 0.009418672 | – | 0.871606688 | – | – | |
| hsa05230 | Central carbon metabolism in cancer | 49.23 | 0.00943342 | – | – | – | – | Core cancer pathway. |
| hsa05163 | Human cytomegalovirus infection | 24 | 0.010897057 | – | – | – | – | |
| hsa04920 | Adipocytokine signaling pathway | 18.84 | 0.011289828 | – | 0.573213367 | – | – | Adipocytokines are implicated in many cancers, including PCa (Housa et al., 2006). |
| hsa05130 | Pathogenic Escherichia coli infection | 10.91 | 0.012638019 | – | 0.914414969 | – | – | |
| hsa05160 | Hepatitis C | 22.58 | 0.012701709 | – | 0.952731561 | – | – | |
| hsa05168 | Herpes simplex infection | 10.81 | 0.012818879 | – | 0.999737262 | – | – | |
| hsa04934 | Cushing syndrome | 22.73 | 0.012968007 | – | – | – | – | |
| hsa04662 | B cell receptor signaling pathway | 42.25 | 0.015323796 | – | 0.871606688 | – | – | |
| hsa05418 | Fluid shear stress and atherosclerosis | 18.71 | 0.016016719 | – | – | – | – | |
| hsa05216 | Thyroid cancer | 70.27 | 0.016672034 | – | 0.77019655 | – | – | |
| hsa05221 | Acute myeloid leukemia | 50 | 0.018273818 | – | 0.916809245 | 0.9737256 | 0.9253648 | |
| hsa04371 | Apelin signaling pathway | 13.14 | 0.019388476 | – | – | – | – | Various apelin peptides can stimulate tumor growth and proliferation of many types of cancer cells, including PCa (Wysocka et al., 2018). |
| hsa05016 | Huntington disease | 10.88 | 0.019575207 | – | 0.887106943 | 1 | 0.9790702 | |
| hsa04911 | Insulin secretion | 11.76 | 0.021091491 | 0.02334547 | – | – | – | |
| hsa04917 | Prolactin signaling pathway | 31.43 | 0.021797194 | – | – | – | – | Prolactin signalling promotes prostate tumorigenesis and may be targeted for therapy (Goffin et al., 2011; Sackmann-Sala and Goffin, 2015). |
| hsa03440 | Homologous recombination | 24.39 | 0.027879334 | – | – | 0.82518643 | 0.88681024 | Homologous recombination offers a model for novel DNA repair targets and therapies in PCa (Bristow et al., 2007). |
| hsa04713 | Circadian entrainment | 10.31 | 0.028299959 | 0.11376372 | – | – | – | |
| hsa03013 | RNA transport | 5.45 | 0.029590861 | – | 0.887106943 | – | – | Many common and specialized mRNA export factors are dysregulated in cancer (Siddiqui and Borden, 2012). |
| hsa04260 | Cardiac muscle contraction | 6.41 | 0.030119546 | – | – | – | 0.92371947 | |
| hsa05161 | Hepatitis B | 31.29 | 0.031074222 | – | – | – | – | |
| hsa04666 | Fc gamma R-mediated phagocytosis | 20.88 | 0.032172546 | – | 0.838868067 | – | – | |
| hsa04976 | Bile secretion | 4.23 | 0.032183139 | – | 0.77019655 | – | – | |
| hsa04024 | cAMP signaling pathway | 14.57 | 0.035154932 | 0.12151133 | – | – | – | Dysregulation cAMP signaling was implicated in many cancer types, including PCa (Fajardo et al., 2014). |
| hsa05226 | Gastric cancer | 30.87 | 0.035466235 | – | – | – | – | |
| hsa04622 | RIG-I-like receptor signaling pathway | 7.14 | 0.036168176 | – | 0.678606672 | 0.998692 | 1 | |
| hsa04150 | mTOR signaling pathway | 16.45 | 0.03639603 | – | 0.608898009 | 0.97279966 | 0.8907857 | mTOR signaling is implicated in prostate cancer progression and androgen deprivation therapy resistance (Edlind and Hsieh, 2014). |
| hsa04064 | NF-kappa B signaling pathway | 17.89 | 0.036565869 | – | 0.999737262 | – | – | The NF-kappa B signaling pathway controls the progression of Pca (Jin et al., 2008). |
| hsa04970 | Salivary secretion | 6.67 | 0.038144831 | 0.35044831 | 0.228920589 | – | – | |
| hsa04658 | Th1 and Th2 cell differentiation | 19.57 | 0.040720473 | – | – | – | – | T helper cells are important in cancer immunity (Knutson and Disis, 2005). |
| hsa04370 | VEGF signaling pathway | 33.9 | 0.043130708 | – | 0.889535144 | – | – | Angiogenesis has been shown to play an important role in tumorigenesis, proliferation and metastasis in PCa. Various promising agents that target VEGF signaling have been tested (Aragon-Ching and Dahut, 2009). |
| hsa04725 | Cholinergic synapse | 18.75 | 0.04793374 | 0.13876451 | 0.129551973 | – | – | |
| hsa00120 | Primary bile acid biosynthesis | 0 | – | – | – | 0.78211117 | <0.001 |
“ID” indicates the Kyoto Encyclopedia of Genes and Genomes (KEGG) ID for the enriched pathway, whereas “Pathway” indicates the KEGG pathway name. “% CGC genes” indicates the percentage of Cancer Gene Census (CGC) genes in the pathway. The lowest Bonferroni-adjusted p value for pathfindR analysis is provided in “pathfindR,” the false discovery rate (FDR)-adjusted p value for Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis is provided in “DAVID,” the FDR-adjusted p value for Signaling Pathway Impact Analysis (SPIA) is presented in “SPIA,” and the FDR-adjusted p values for Gene Set Enrichment Analysis (GSEA) and GSEAPreranked are presented in “GSEA” and “GSEAPreranked,” respectively. Significant p values (i.e., adjusted p value < 0.05) are given in bold font. “-“ indicates the pathway was not found to be enriched by the given tool. If a pathway is relevant to PCa, a brief description of its relevance is provided in “Brief Description.”