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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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: DNAJC3

Gene summary for DNAJC3

Gene summary.

Gene information	Species	Human
	Gene symbol	DNAJC3
	Gene ID	5611
	Gene name	DnaJ heat shock protein family (Hsp40) member C3
	Gene Alias	ACPHD
	Cytomap	13q32.1
	Gene Type	protein-coding
	GO ID	GO:0001932
	UniProtAcc	A8KA82

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Malignant transformation analysis

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

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
5611	DNAJC3	LZE2D	Human	Esophagus	HGIN	3.97e-04	3.89e-01	0.0642
5611	DNAJC3	LZE4T	Human	Esophagus	ESCC	2.05e-11	4.15e-01	0.0811
5611	DNAJC3	LZE5T	Human	Esophagus	ESCC	4.21e-05	4.38e-01	0.0514
5611	DNAJC3	LZE7T	Human	Esophagus	ESCC	4.74e-10	5.65e-01	0.0667
5611	DNAJC3	LZE8T	Human	Esophagus	ESCC	1.12e-12	3.60e-01	0.067
5611	DNAJC3	LZE20T	Human	Esophagus	ESCC	1.20e-05	1.24e-01	0.0662
5611	DNAJC3	LZE22T	Human	Esophagus	ESCC	2.57e-04	3.91e-01	0.068
5611	DNAJC3	LZE24T	Human	Esophagus	ESCC	4.67e-16	4.77e-01	0.0596
5611	DNAJC3	P1T-E	Human	Esophagus	ESCC	8.11e-14	7.16e-01	0.0875
5611	DNAJC3	P2T-E	Human	Esophagus	ESCC	1.52e-44	7.85e-01	0.1177
5611	DNAJC3	P4T-E	Human	Esophagus	ESCC	5.61e-37	8.57e-01	0.1323
5611	DNAJC3	P5T-E	Human	Esophagus	ESCC	1.10e-08	2.75e-01	0.1327
5611	DNAJC3	P8T-E	Human	Esophagus	ESCC	4.73e-43	9.96e-01	0.0889
5611	DNAJC3	P9T-E	Human	Esophagus	ESCC	3.22e-27	5.64e-01	0.1131
5611	DNAJC3	P10T-E	Human	Esophagus	ESCC	1.29e-30	6.99e-01	0.116
5611	DNAJC3	P11T-E	Human	Esophagus	ESCC	2.28e-29	1.15e+00	0.1426
5611	DNAJC3	P12T-E	Human	Esophagus	ESCC	1.24e-53	9.78e-01	0.1122
5611	DNAJC3	P15T-E	Human	Esophagus	ESCC	9.30e-35	6.58e-01	0.1149
5611	DNAJC3	P16T-E	Human	Esophagus	ESCC	2.57e-54	1.05e+00	0.1153
5611	DNAJC3	P17T-E	Human	Esophagus	ESCC	6.03e-13	5.56e-01	0.1278

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		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

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗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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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:000641727	Esophagus	HGIN	regulation of translation	139/2587	468/18723	1.46e-19	7.98e-17	139
GO:000641320	Esophagus	HGIN	translational initiation	55/2587	118/18723	7.33e-18	2.31e-15	55
GO:000645720	Esophagus	HGIN	protein folding	75/2587	212/18723	1.61e-15	3.86e-13	75
GO:003497625	Esophagus	HGIN	response to endoplasmic reticulum stress	81/2587	256/18723	1.47e-13	2.32e-11	81
GO:004572720	Esophagus	HGIN	positive regulation of translation	49/2587	136/18723	5.88e-11	6.30e-09	49
GO:003596625	Esophagus	HGIN	response to topologically incorrect protein	54/2587	159/18723	8.53e-11	8.89e-09	54
GO:000644610	Esophagus	HGIN	regulation of translational initiation	34/2587	79/18723	2.09e-10	1.97e-08	34
GO:000698625	Esophagus	HGIN	response to unfolded protein	48/2587	137/18723	2.80e-10	2.54e-08	48
GO:003425020	Esophagus	HGIN	positive regulation of cellular amide metabolic process	53/2587	162/18723	6.01e-10	5.15e-08	53
GO:00435555	Esophagus	HGIN	regulation of translation in response to stress	10/2587	20/18723	1.22e-04	2.53e-03	10
GO:004593626	Esophagus	HGIN	negative regulation of phosphate metabolic process	89/2587	441/18723	1.24e-04	2.54e-03	89
GO:001056326	Esophagus	HGIN	negative regulation of phosphorus metabolic process	89/2587	442/18723	1.34e-04	2.71e-03	89
GO:004232620	Esophagus	HGIN	negative regulation of phosphorylation	78/2587	385/18723	2.77e-04	4.77e-03	78
GO:000926618	Esophagus	HGIN	response to temperature stimulus	42/2587	178/18723	2.91e-04	4.98e-03	42
GO:000193320	Esophagus	HGIN	negative regulation of protein phosphorylation	69/2587	342/18723	6.81e-04	9.26e-03	69
GO:00435585	Esophagus	HGIN	regulation of translational initiation in response to stress	7/2587	14/18723	1.34e-03	1.57e-02	7
GO:00364905	Esophagus	HGIN	regulation of translation in response to endoplasmic reticulum stress	6/2587	11/18723	1.71e-03	1.86e-02	6
GO:000961517	Esophagus	HGIN	response to virus	69/2587	367/18723	4.39e-03	3.86e-02	69
GO:003238618	Esophagus	ESCC	regulation of intracellular transport	243/8552	337/18723	3.20e-23	7.25e-21	243
GO:0006091110	Esophagus	ESCC	generation of precursor metabolites and energy	331/8552	490/18723	3.86e-23	8.45e-21	331

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414139	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
hsa0516420	Esophagus	HGIN	Influenza A	42/1383	171/8465	3.41e-03	2.54e-02	2.02e-02	42
hsa04141114	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
hsa05164110	Esophagus	HGIN	Influenza A	42/1383	171/8465	3.41e-03	2.54e-02	2.02e-02	42
hsa04141211	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa0516425	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122
hsa04141310	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa0516435	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122
hsa0414114	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0516410	Liver	Cirrhotic	Influenza A	66/2530	171/8465	8.56e-03	2.91e-02	1.79e-02	66
hsa0414115	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0516411	Liver	Cirrhotic	Influenza A	66/2530	171/8465	8.56e-03	2.91e-02	1.79e-02	66
hsa0414122	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0516421	Liver	HCC	Influenza A	101/4020	171/8465	1.41e-03	5.07e-03	2.82e-03	101
hsa0414132	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0516431	Liver	HCC	Influenza A	101/4020	171/8465	1.41e-03	5.07e-03	2.82e-03	101
hsa0414116	Lung	IAC	Protein processing in endoplasmic reticulum	37/1053	174/8465	6.53e-04	5.73e-03	3.81e-03	37
hsa0516412	Lung	IAC	Influenza A	35/1053	171/8465	1.82e-03	1.00e-02	6.66e-03	35
hsa0414117	Lung	IAC	Protein processing in endoplasmic reticulum	37/1053	174/8465	6.53e-04	5.73e-03	3.81e-03	37
hsa0516413	Lung	IAC	Influenza A	35/1053	171/8465	1.82e-03	1.00e-02	6.66e-03	35

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon 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

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

DNAJC3

SNV

Missense_Mutation

c.1090G>A

p.Glu364Lys

p.E364K

Q13217

protein_coding

tolerated(0.34)

benign(0.021)

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

DNAJC3

SNV

Missense_Mutation

rs533997604

c.467G>A

p.Arg156His

p.R156H

Q13217

protein_coding

tolerated(0.22)

benign(0.005)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DNAJC3

SNV

Missense_Mutation

c.640N>A

p.Ala214Thr

p.A214T

Q13217

protein_coding

tolerated(0.93)

benign(0.003)

TCGA-C8-A26Z-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

DNAJC3

SNV

Missense_Mutation

rs778884455

c.1423N>A

p.Gly475Ser

p.G475S

Q13217

protein_coding

tolerated(0.35)

benign(0.124)

TCGA-D8-A1Y1-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

DNAJC3

SNV

Missense_Mutation

novel

c.337C>G

p.His113Asp

p.H113D

Q13217

protein_coding

deleterious(0.02)

benign(0.132)

TCGA-E9-A226-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

tamoxiphen

DNAJC3

insertion

Frame_Shift_Ins

novel

c.596dupT

p.Glu201ArgfsTer5

p.E201Rfs*5

Q13217

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

DNAJC3

insertion

Nonsense_Mutation

novel

c.597_598insTTGTAAGGCACATTTATATACTTCGACATGTCACATACCAC

p.Lys200LeufsTer2

p.K200Lfs*2

Q13217

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

DNAJC3

SNV

Missense_Mutation

rs144153992

c.1483G>A

p.Gly495Arg

p.G495R

Q13217

protein_coding

deleterious(0)

possibly_damaging(0.904)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DNAJC3

SNV

Missense_Mutation

c.917T>C

p.Val306Ala

p.V306A

Q13217

protein_coding

tolerated(0.46)

benign(0)

TCGA-AA-3815-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

DNAJC3

SNV

Missense_Mutation

novel

c.82N>A

p.Gly28Ser

p.G28S

Q13217

protein_coding

tolerated(0.13)

benign(0.013)

TCGA-AA-3949-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID

Symbol

Category

Interaction Types

Drug Claim Name

Drug Name

PMIDs

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