Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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Center for Computational Systems Medicine
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Gene summary

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Malignant transformation analysis

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Malignant transformation related pathway analysis

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Cell-cell communication analysis

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Single-cell gene regulatory network inference analysis

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Somatic mutation of malignant transformation related genes

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Related drugs of malignant transformation related genes

Gene: HSPA4

Gene summary for HSPA4

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

HSPA4

Gene ID

3308

Gene nameheat shock protein family A (Hsp70) member 4
Gene AliasAPG-2
Cytomap5q31.1
Gene Typeprotein-coding
GO ID

GO:0006605

UniProtAcc

P34932


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Malignant transformation analysis

check button Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells
check button Malignant transformation involving gene list.
Entrez IDSymbolReplicatesSpeciesOrganTissueAdj P-valueLog2FCMalignancy
3308HSPA4LZE2THumanEsophagusESCC3.36e-031.20e+000.082
3308HSPA4LZE4THumanEsophagusESCC9.06e-146.69e-010.0811
3308HSPA4LZE5THumanEsophagusESCC4.25e-03-2.22e-030.0514
3308HSPA4LZE7THumanEsophagusESCC7.23e-034.92e-010.0667
3308HSPA4LZE20THumanEsophagusESCC1.79e-031.08e-010.0662
3308HSPA4LZE22THumanEsophagusESCC1.09e-027.19e-010.068
3308HSPA4LZE24THumanEsophagusESCC4.96e-125.83e-010.0596
3308HSPA4LZE6THumanEsophagusESCC1.06e-085.01e-010.0845
3308HSPA4P1T-EHumanEsophagusESCC6.01e-042.63e-010.0875
3308HSPA4P2T-EHumanEsophagusESCC1.57e-408.47e-010.1177
3308HSPA4P4T-EHumanEsophagusESCC7.80e-248.86e-010.1323
3308HSPA4P5T-EHumanEsophagusESCC3.05e-358.90e-010.1327
3308HSPA4P8T-EHumanEsophagusESCC2.94e-173.24e-020.0889
3308HSPA4P9T-EHumanEsophagusESCC2.63e-133.10e-010.1131
3308HSPA4P10T-EHumanEsophagusESCC5.06e-122.95e-010.116
3308HSPA4P11T-EHumanEsophagusESCC1.48e-146.52e-010.1426
3308HSPA4P12T-EHumanEsophagusESCC8.83e-481.01e+000.1122
3308HSPA4P15T-EHumanEsophagusESCC5.08e-269.43e-010.1149
3308HSPA4P16T-EHumanEsophagusESCC3.24e-226.51e-010.1153
3308HSPA4P17T-EHumanEsophagusESCC1.33e-106.99e-010.1278
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check button Transcriptomic changes along malignancy continuum.
TissueExpression DynamicsAbbreviation
EsophagusThe image shows the transcriptomic changes along malignancy continuum.log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.ESCC: Esophageal squamous cell carcinoma
HGIN: High-grade intraepithelial neoplasias
LGIN: Low-grade intraepithelial neoplasias
LiverThe image shows the transcriptomic changes along malignancy continuum.log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.HCC: Hepatocellular carcinoma
NAFLD: Non-alcoholic fatty liver disease
Oral CavityThe image shows the transcriptomic changes along malignancy continuum.log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.EOLP: Erosive Oral lichen planus
LP: leukoplakia
NEOLP: Non-erosive oral lichen planus
OSCC: Oral squamous cell carcinoma
ProstateThe image shows the transcriptomic changes along malignancy continuum.log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.BPH: Benign Prostatic Hyperplasia
SkinThe image shows the transcriptomic changes along malignancy continuum.log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.AK: Actinic keratosis
cSCC: Cutaneous squamous cell carcinoma
SCCIS:squamous cell carcinoma in situ
ThyroidThe image shows the transcriptomic changes along malignancy continuum.log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.ATC: Anaplastic thyroid cancer
HT: Hashimoto's thyroiditis
PTC: Papillary thyroid cancer
∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

check buttonFind out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer
check button Figure of enriched GO biological processes.
TissueDisease StageEnriched GO biological Processes
ColorectumADGO analysis - Figure of enriched GO biological processes: Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).
ColorectumSERGO analysis - Figure of enriched GO biological processes: Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).
ColorectumMSSGO analysis - Figure of enriched GO biological processes: Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).
ColorectumMSI-HGO analysis - Figure of enriched GO biological processes: Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).
ColorectumFAPGO analysis - Figure of enriched GO biological processes: Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).
∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).
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check button Enriched GO biological processes.
GO IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustCount
GO:0072594110EsophagusESCCestablishment of protein localization to organelle311/8552422/187233.02e-322.13e-29311
GO:0006605111EsophagusESCCprotein targeting229/8552314/187234.93e-231.01e-20229
GO:0006457110EsophagusESCCprotein folding163/8552212/187231.13e-201.74e-18163
GO:0006839110EsophagusESCCmitochondrial transport187/8552254/187238.35e-209.81e-18187
GO:0035966111EsophagusESCCresponse to topologically incorrect protein125/8552159/187231.44e-171.27e-15125
GO:0090150110EsophagusESCCestablishment of protein localization to membrane182/8552260/187231.27e-158.19e-14182
GO:0072655110EsophagusESCCestablishment of protein localization to mitochondrion97/8552120/187232.17e-151.33e-1397
GO:0070585110EsophagusESCCprotein localization to mitochondrion100/8552125/187232.96e-151.77e-13100
GO:001703818EsophagusESCCprotein import149/8552206/187235.90e-153.31e-13149
GO:0006986111EsophagusESCCresponse to unfolded protein107/8552137/187237.01e-153.87e-13107
GO:000700619EsophagusESCCmitochondrial membrane organization93/8552116/187232.16e-141.11e-1293
GO:0006626110EsophagusESCCprotein targeting to mitochondrion81/8552100/187233.60e-131.67e-1181
GO:005120515EsophagusESCCprotein insertion into membrane46/855257/187235.90e-081.04e-0646
GO:009015118EsophagusESCCestablishment of protein localization to mitochondrial membrane26/855230/187233.79e-064.12e-0526
GO:005120416EsophagusESCCprotein insertion into mitochondrial membrane21/855225/187239.12e-056.54e-0421
GO:005113119EsophagusESCCchaperone-mediated protein complex assembly17/855223/187235.73e-032.13e-0217
GO:00064577LiverCirrhoticprotein folding114/4634212/187239.23e-202.31e-17114
GO:007259412LiverCirrhoticestablishment of protein localization to organelle189/4634422/187231.01e-192.45e-17189
GO:00359667LiverCirrhoticresponse to topologically incorrect protein91/4634159/187232.07e-183.60e-1691
GO:00066057LiverCirrhoticprotein targeting148/4634314/187233.86e-186.20e-16148
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa05417211EsophagusESCCLipid and atherosclerosis143/4205215/84653.30e-072.45e-061.26e-06143
hsa04530211EsophagusESCCTight junction105/4205169/84656.73e-042.23e-031.14e-03105
hsa0461230EsophagusESCCAntigen processing and presentation51/420578/84653.57e-039.34e-034.78e-0351
hsa05417310EsophagusESCCLipid and atherosclerosis143/4205215/84653.30e-072.45e-061.26e-06143
hsa04530310EsophagusESCCTight junction105/4205169/84656.73e-042.23e-031.14e-03105
hsa04612114EsophagusESCCAntigen processing and presentation51/420578/84653.57e-039.34e-034.78e-0351
hsa0453022LiverCirrhoticTight junction82/2530169/84652.14e-072.85e-061.76e-0682
hsa0461214LiverCirrhoticAntigen processing and presentation36/253078/84651.69e-038.01e-034.94e-0336
hsa0541722LiverCirrhoticLipid and atherosclerosis80/2530215/84651.18e-023.81e-022.35e-0280
hsa0453032LiverCirrhoticTight junction82/2530169/84652.14e-072.85e-061.76e-0682
hsa0461215LiverCirrhoticAntigen processing and presentation36/253078/84651.69e-038.01e-034.94e-0336
hsa0541732LiverCirrhoticLipid and atherosclerosis80/2530215/84651.18e-023.81e-022.35e-0280
hsa0453042LiverHCCTight junction110/4020169/84652.45e-062.28e-051.27e-05110
hsa0541742LiverHCCLipid and atherosclerosis118/4020215/84651.66e-023.92e-022.18e-02118
hsa0453052LiverHCCTight junction110/4020169/84652.45e-062.28e-051.27e-05110
hsa0541752LiverHCCLipid and atherosclerosis118/4020215/84651.66e-023.92e-022.18e-02118
hsa0541730Oral cavityOSCCLipid and atherosclerosis131/3704215/84652.20e-071.45e-067.37e-07131
hsa0453030Oral cavityOSCCTight junction102/3704169/84658.68e-063.93e-052.00e-05102
hsa0461229Oral cavityOSCCAntigen processing and presentation47/370478/84652.37e-036.35e-033.23e-0347
hsa05417113Oral cavityOSCCLipid and atherosclerosis131/3704215/84652.20e-071.45e-067.37e-07131
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Cell-cell communication analysis

check buttonIdentification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states
LigandReceptorLRpairPathwayTissueDisease Stage
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Single-cell gene regulatory network inference analysis

check buttonFind out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states
TFCell TypeTissueDisease StageTarget GeneRSSRegulon Activity
∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.
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Somatic mutation of malignant transformation related genes

check buttonAnnotation of somatic variants for genes involved in malignant transformation
Hugo SymbolVariant ClassVariant ClassificationdbSNP RSHGVScHGVSpHGVSp ShortSWISSPROTBIOTYPESIFTPolyPhenTumor Sample BarcodeTissueHistologySexAgeStageTherapy TypesDrugsOutcome
HSPA4SNVMissense_Mutationc.807G>Cp.Glu269Aspp.E269DP34932protein_codingdeleterious(0)probably_damaging(0.992)TCGA-A2-A0T0-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapytaxotereSD
HSPA4SNVMissense_Mutationc.268N>Tp.Asp90Tyrp.D90YP34932protein_codingtolerated(0.07)possibly_damaging(0.678)TCGA-AC-A23H-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownPD
HSPA4SNVMissense_Mutationc.794N>Ap.Arg265Glnp.R265QP34932protein_codingdeleterious(0)probably_damaging(0.997)TCGA-AN-A046-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
HSPA4SNVMissense_Mutationc.254C>Gp.Ser85Cysp.S85CP34932protein_codingdeleterious(0.04)possibly_damaging(0.557)TCGA-AN-A0XW-01Breastbreast invasive carcinomaFemale<65III/IVUnknownUnknownSD
HSPA4SNVMissense_Mutationc.2084G>Tp.Arg695Leup.R695LP34932protein_codingdeleterious(0.02)probably_damaging(0.993)TCGA-E9-A244-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapycyclophosphamideSD
HSPA4SNVMissense_Mutationnovelc.455N>Tp.Glu152Valp.E152VP34932protein_codingdeleterious(0)possibly_damaging(0.856)TCGA-S3-AA11-01Breastbreast invasive carcinomaFemale>=65I/IIHormone TherapyletrozoleCR
HSPA4deletionIn_Frame_Delnovelc.2394_2408delAAATGCAGAGCAGAAp.Lys798_Gln802delp.K798_Q802delP34932protein_codingTCGA-E2-A1LS-01Breastbreast invasive carcinomaFemale<65I/IIUnspecificCyclophosphamideSD
HSPA4SNVMissense_Mutationnovelc.2243A>Gp.Lys748Argp.K748RP34932protein_codingtolerated(0.28)benign(0.001)TCGA-2W-A8YY-01Cervixcervical & endocervical cancerFemale<65I/IIChemotherapycisplatinCR
HSPA4SNVMissense_Mutationc.577N>Ap.Glu193Lysp.E193KP34932protein_codingdeleterious(0)probably_damaging(0.994)TCGA-IR-A3LH-01Cervixcervical & endocervical cancerFemale<65I/IIChemotherapycisplatinCR
HSPA4SNVMissense_Mutationc.1633N>Cp.Glu545Glnp.E545QP34932protein_codingtolerated(0.27)benign(0.214)TCGA-LP-A5U2-01Cervixcervical & endocervical cancerFemale<65III/IVUnknownUnknownSD
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Related drugs of malignant transformation related genes

check buttonIdentification of chemicals and drugs interact with genes involved in malignant transfromation
(DGIdb 4.0)
Entrez IDSymbolCategoryInteraction TypesDrug Claim NameDrug NamePMIDs
3308HSPA4NAUREAUREA7548155
3308HSPA4NAPHOSPHODIESTERASE INHIBITOR9383212
3308HSPA4NAAEG-33773
3308HSPA4NATRAIL12460647
3308HSPA4NAGOSSYPOLGOSSYPOL2193225
3308HSPA4NANIMESULIDENIMESULIDE9645681
3308HSPA4NAKETANSERINKETANSERIN9864262
3308HSPA4NACYTARABINECYTARABINE12530536
3308HSPA4NAPOH17024970
3308HSPA4NACISPLATINCISPLATIN11478701
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