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: GOLGA4

Gene summary for GOLGA4

Gene summary.

Gene information	Species	Human
	Gene symbol	GOLGA4
	Gene ID	2803
	Gene name	golgin A4
	Gene Alias	CRPF46
	Cytomap	3p22.2
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	Q13439

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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
2803	GOLGA4	CA_HPV_1	Human	Cervix	CC	2.95e-09	-2.78e-01	0.0264
2803	GOLGA4	N_HPV_1	Human	Cervix	N_HPV	4.28e-03	-2.64e-01	0.0079
2803	GOLGA4	CCI_2	Human	Cervix	CC	2.02e-05	5.84e-01	0.5249
2803	GOLGA4	CCI_3	Human	Cervix	CC	1.79e-03	6.17e-01	0.516
2803	GOLGA4	CCII_1	Human	Cervix	CC	3.07e-03	-4.62e-01	0.3249
2803	GOLGA4	Tumor	Human	Cervix	CC	1.10e-11	-4.53e-01	0.1241
2803	GOLGA4	sample3	Human	Cervix	CC	4.35e-12	-3.35e-01	0.1387
2803	GOLGA4	H2	Human	Cervix	HSIL_HPV	1.93e-04	2.46e-01	0.0632
2803	GOLGA4	T3	Human	Cervix	CC	3.96e-06	-3.62e-01	0.1389
2803	GOLGA4	HTA11_3410_2000001011	Human	Colorectum	AD	1.64e-43	-9.37e-01	0.0155
2803	GOLGA4	HTA11_2487_2000001011	Human	Colorectum	SER	1.13e-07	-5.83e-01	-0.1808
2803	GOLGA4	HTA11_2951_2000001011	Human	Colorectum	AD	4.20e-05	-9.17e-01	0.0216
2803	GOLGA4	HTA11_3361_2000001011	Human	Colorectum	AD	4.49e-11	-6.91e-01	-0.1207
2803	GOLGA4	HTA11_5212_2000001011	Human	Colorectum	AD	1.38e-05	-7.55e-01	-0.2061
2803	GOLGA4	HTA11_5216_2000001011	Human	Colorectum	SER	4.28e-02	-5.48e-01	-0.1462
2803	GOLGA4	HTA11_9341_2000001011	Human	Colorectum	SER	1.18e-03	-8.68e-01	-0.00410000000000005
2803	GOLGA4	HTA11_7862_2000001011	Human	Colorectum	AD	1.25e-11	-8.54e-01	-0.0179
2803	GOLGA4	HTA11_866_3004761011	Human	Colorectum	AD	3.55e-24	-8.24e-01	0.096
2803	GOLGA4	HTA11_4255_2000001011	Human	Colorectum	SER	2.42e-03	-7.21e-01	0.0446
2803	GOLGA4	HTA11_9408_2000001011	Human	Colorectum	AD	1.23e-04	-8.70e-01	0.0451

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:006195122	Skin	cSCC	establishment of protein localization to plasma membrane	30/4864	60/18723	5.67e-05	5.67e-04	30
GO:004300115	Skin	cSCC	Golgi to plasma membrane protein transport	22/4864	40/18723	8.93e-05	8.37e-04	22
GO:0032535111	Skin	cSCC	regulation of cellular component size	131/4864	383/18723	1.89e-04	1.59e-03	131
GO:000155824	Skin	cSCC	regulation of cell growth	140/4864	414/18723	2.07e-04	1.72e-03	140
GO:001072016	Skin	cSCC	positive regulation of cell development	105/4864	298/18723	2.30e-04	1.89e-03	105
GO:003134622	Skin	cSCC	positive regulation of cell projection organization	120/4864	353/18723	4.49e-04	3.44e-03	120
GO:005076913	Skin	cSCC	positive regulation of neurogenesis	80/4864	225/18723	8.85e-04	6.07e-03	80
GO:003030722	Skin	cSCC	positive regulation of cell growth	61/4864	166/18723	1.39e-03	8.78e-03	61
GO:005076722	Skin	cSCC	regulation of neurogenesis	118/4864	364/18723	3.32e-03	1.81e-02	118
GO:001097522	Skin	cSCC	regulation of neuron projection development	141/4864	445/18723	3.72e-03	1.99e-02	141
GO:006156422	Skin	cSCC	axon development	146/4864	467/18723	5.50e-03	2.73e-02	146
GO:00507729	Skin	cSCC	positive regulation of axonogenesis	31/4864	79/18723	6.63e-03	3.23e-02	31
GO:006056023	Skin	cSCC	developmental growth involved in morphogenesis	78/4864	234/18723	7.08e-03	3.40e-02	78
GO:004592719	Skin	cSCC	positive regulation of growth	85/4864	259/18723	8.03e-03	3.73e-02	85
GO:199013823	Skin	cSCC	neuron projection extension	59/4864	172/18723	9.20e-03	4.20e-02	59
GO:005196213	Skin	cSCC	positive regulation of nervous system development	88/4864	272/18723	1.07e-02	4.66e-02	88
GO:00325355	Stomach	GC	regulation of cellular component size	44/1159	383/18723	5.66e-05	1.31e-03	44
GO:003253511	Stomach	CAG with IM	regulation of cellular component size	41/1050	383/18723	5.55e-05	1.38e-03	41
GO:00726596	Stomach	CAG with IM	protein localization to plasma membrane	27/1050	284/18723	5.25e-03	4.19e-02	27
GO:003253521	Stomach	CSG	regulation of cellular component size	41/1034	383/18723	3.94e-05	1.04e-03	41

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

GOLGA4

SNV

Missense_Mutation

c.3932A>G

p.Asn1311Ser

p.N1311S

Q13439

protein_coding

tolerated(0.75)

benign(0.001)

TCGA-A8-A07L-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

GOLGA4

SNV

Missense_Mutation

c.3722N>A

p.Ile1241Asn

p.I1241N

Q13439

protein_coding

tolerated(0.55)

benign(0.037)

TCGA-A8-A0A1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

GOLGA4

SNV

Missense_Mutation

rs768808136

c.296N>A

p.Arg99Gln

p.R99Q

Q13439

protein_coding

deleterious(0.02)

probably_damaging(0.996)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GOLGA4

SNV

Missense_Mutation

rs764030527

c.4237N>A

p.Glu1413Lys

p.E1413K

Q13439

protein_coding

deleterious(0)

possibly_damaging(0.864)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GOLGA4

SNV

Missense_Mutation

rs750023676

c.6565N>A

p.Glu2189Lys

p.E2189K

Q13439

protein_coding

deleterious(0)

probably_damaging(0.922)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GOLGA4

SNV

Missense_Mutation

novel

c.431G>A

p.Ser144Asn

p.S144N

Q13439

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AO-A1KP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

fluorouracil

GOLGA4

SNV

Missense_Mutation

c.1411N>A

p.Glu471Lys

p.E471K

Q13439

protein_coding

deleterious(0)

probably_damaging(0.959)

TCGA-BH-A0AW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

GOLGA4

SNV

Missense_Mutation

c.6097N>A

p.Glu2033Lys

p.E2033K

Q13439

protein_coding

deleterious(0)

probably_damaging(0.911)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

GOLGA4

SNV

Missense_Mutation

c.1885N>A

p.Val629Ile

p.V629I

Q13439

protein_coding

tolerated(0.36)

benign(0)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GOLGA4

SNV

Missense_Mutation

c.1372N>A

p.Glu458Lys

p.E458K

Q13439

protein_coding

deleterious(0.02)

probably_damaging(0.922)

TCGA-BH-A18K-01

Breast

breast invasive carcinoma

Female

<65

I/II

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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