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: AUP1

Gene summary for AUP1

Gene summary.

Gene information	Species	Human
	Gene symbol	AUP1
	Gene ID	550
	Gene name	AUP1 lipid droplet regulating VLDL assembly factor
	Gene Alias	AUP1
	Cytomap	2p13.1
	Gene Type	protein-coding
	GO ID	GO:0006508
	UniProtAcc	Q9Y679

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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
550	AUP1	HTA11_2487_2000001011	Human	Colorectum	SER	1.18e-05	3.34e-01	-0.1808
550	AUP1	HTA11_1938_2000001011	Human	Colorectum	AD	6.90e-05	3.16e-01	-0.0811
550	AUP1	HTA11_78_2000001011	Human	Colorectum	AD	5.47e-06	2.19e-01	-0.1088
550	AUP1	HTA11_347_2000001011	Human	Colorectum	AD	8.33e-14	3.47e-01	-0.1954
550	AUP1	HTA11_3361_2000001011	Human	Colorectum	AD	1.16e-04	3.31e-01	-0.1207
550	AUP1	HTA11_83_2000001011	Human	Colorectum	SER	2.98e-06	2.53e-01	-0.1526
550	AUP1	HTA11_696_2000001011	Human	Colorectum	AD	5.53e-11	4.63e-01	-0.1464
550	AUP1	HTA11_866_2000001011	Human	Colorectum	AD	1.20e-06	2.60e-01	-0.1001
550	AUP1	HTA11_1391_2000001011	Human	Colorectum	AD	2.53e-09	3.72e-01	-0.059
550	AUP1	HTA11_5216_2000001011	Human	Colorectum	SER	3.52e-04	2.83e-01	-0.1462
550	AUP1	HTA11_866_3004761011	Human	Colorectum	AD	7.44e-10	3.52e-01	0.096
550	AUP1	HTA11_4255_2000001011	Human	Colorectum	SER	2.84e-03	3.09e-01	0.0446
550	AUP1	HTA11_7663_2000001011	Human	Colorectum	SER	1.89e-04	6.18e-01	0.0131
550	AUP1	HTA11_10623_2000001011	Human	Colorectum	AD	4.07e-02	3.95e-01	-0.0177
550	AUP1	HTA11_10711_2000001011	Human	Colorectum	AD	2.06e-05	2.98e-01	0.0338
550	AUP1	HTA11_7696_3000711011	Human	Colorectum	AD	3.27e-05	2.39e-01	0.0674
550	AUP1	HTA11_6818_2000001011	Human	Colorectum	AD	1.94e-02	2.87e-01	0.0112
550	AUP1	HTA11_11156_2000001011	Human	Colorectum	AD	1.98e-03	4.62e-01	0.0397
550	AUP1	HTA11_6818_2000001021	Human	Colorectum	AD	4.15e-03	3.02e-01	0.0588
550	AUP1	HTA11_99999970781_79442	Human	Colorectum	MSS	3.18e-02	2.64e-01	0.294

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:1903513	Colorectum	SER	endoplasmic reticulum to cytosol transport	12/2897	29/18723	7.22e-04	9.44e-03	12
GO:00717121	Colorectum	SER	ER-associated misfolded protein catabolic process	7/2897	12/18723	8.12e-04	1.01e-02	7
GO:00365031	Colorectum	SER	ERAD pathway	28/2897	107/18723	2.92e-03	2.59e-02	28
GO:0032527	Colorectum	SER	protein exit from endoplasmic reticulum	15/2897	48/18723	4.60e-03	3.64e-02	15
GO:0071218	Colorectum	SER	cellular response to misfolded protein	9/2897	23/18723	5.20e-03	3.95e-02	9
GO:00104982	Colorectum	MSS	proteasomal protein catabolic process	157/3467	490/18723	2.39e-13	5.25e-11	157
GO:00431612	Colorectum	MSS	proteasome-mediated ubiquitin-dependent protein catabolic process	127/3467	412/18723	7.70e-10	6.32e-08	127
GO:00162362	Colorectum	MSS	macroautophagy	93/3467	291/18723	2.08e-08	1.17e-06	93
GO:00349762	Colorectum	MSS	response to endoplasmic reticulum stress	81/3467	256/18723	2.65e-07	1.10e-05	81
GO:00359672	Colorectum	MSS	cellular response to topologically incorrect protein	42/3467	116/18723	4.99e-06	1.38e-04	42
GO:00359662	Colorectum	MSS	response to topologically incorrect protein	53/3467	159/18723	5.50e-06	1.49e-04	53
GO:00619122	Colorectum	MSS	selective autophagy	27/3467	68/18723	3.68e-05	7.09e-04	27
GO:00717122	Colorectum	MSS	ER-associated misfolded protein catabolic process	7/3467	12/18723	2.45e-03	1.97e-02	7
GO:00065152	Colorectum	MSS	protein quality control for misfolded or incompletely synthesized proteins	12/3467	28/18723	2.53e-03	2.02e-02	12
GO:00712181	Colorectum	MSS	cellular response to misfolded protein	10/3467	23/18723	5.06e-03	3.47e-02	10
GO:00108761	Colorectum	MSS	lipid localization	104/3467	448/18723	6.76e-03	4.38e-02	104
GO:001049826	Esophagus	HGIN	proteasomal protein catabolic process	139/2587	490/18723	1.20e-17	3.41e-15	139
GO:004316126	Esophagus	HGIN	proteasome-mediated ubiquitin-dependent protein catabolic process	114/2587	412/18723	7.00e-14	1.20e-11	114
GO:003497625	Esophagus	HGIN	response to endoplasmic reticulum stress	81/2587	256/18723	1.47e-13	2.32e-11	81
GO:003596625	Esophagus	HGIN	response to topologically incorrect protein	54/2587	159/18723	8.53e-11	8.89e-09	54

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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

AUP1

SNV

Missense_Mutation

c.1003N>C

p.Glu335Gln

p.E335Q

Q9Y679

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A2-A0D0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

AUP1

SNV

Missense_Mutation

c.340N>T

p.Pro114Ser

p.P114S

Q9Y679

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A7-A13D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

AUP1

SNV

Missense_Mutation

novel

c.896C>T

p.Thr299Ile

p.T299I

Q9Y679

protein_coding

tolerated(0.18)

benign(0)

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

AUP1

insertion

Frame_Shift_Ins

novel

c.704_705insGAATGGAATTATGGAGCTACTACGGCAAAGCCTGAATAATATC

p.Ala236AsnfsTer17

p.A236Nfs*17

Q9Y679

protein_coding

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

AUP1

insertion

In_Frame_Ins

novel

c.897_898insTTTATATTTTTTGCCATGTTGCCC

p.Thr299_Leu300insPheIlePhePheAlaMetLeuPro

p.T299_L300insFIFFAMLP

Q9Y679

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

AUP1

SNV

Missense_Mutation

novel

c.4G>A

p.Glu2Lys

p.E2K

Q9Y679

protein_coding

deleterious_low_confidence(0.02)

benign(0.001)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

AUP1

SNV

Missense_Mutation

rs755973491

c.679N>T

p.Arg227Cys

p.R227C

Q9Y679

protein_coding

deleterious(0)

benign(0.292)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

AUP1

SNV

Missense_Mutation

c.40N>C

p.Asp14His

p.D14H

Q9Y679

protein_coding

tolerated(0.14)

probably_damaging(0.971)

TCGA-JX-A3Q0-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

AUP1

SNV

Missense_Mutation

novel

c.43N>C

p.Ser15Pro

p.S15P

Q9Y679

protein_coding

tolerated(0.21)

possibly_damaging(0.736)

TCGA-5M-AAT5-01

Colorectum

colon adenocarcinoma

Unknown

I/II

Unknown

AUP1

SNV

Missense_Mutation

rs746000640

c.1145N>A

p.Arg382Gln

p.R382Q

Q9Y679

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AZ-6601-01

Colorectum

colon adenocarcinoma

Male

>=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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