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	C08	Human	Oral cavity	OSCC	6.82e-98	2.14e+00	0.1919
550	AUP1	C09	Human	Oral cavity	OSCC	2.13e-16	6.53e-01	0.1431
550	AUP1	LN22	Human	Oral cavity	OSCC	2.28e-12	1.44e+00	0.1733
550	AUP1	LN38	Human	Oral cavity	OSCC	7.00e-12	1.66e+00	0.168
550	AUP1	LN46	Human	Oral cavity	OSCC	3.98e-38	1.37e+00	0.1666
550	AUP1	LP15	Human	Oral cavity	LP	1.13e-14	2.16e+00	0.2174
550	AUP1	LP17	Human	Oral cavity	LP	2.06e-17	1.53e+00	0.2349
550	AUP1	SYSMH1	Human	Oral cavity	OSCC	9.09e-38	9.62e-01	0.1127
550	AUP1	SYSMH2	Human	Oral cavity	OSCC	1.58e-34	1.21e+00	0.2326
550	AUP1	SYSMH3	Human	Oral cavity	OSCC	3.19e-50	1.54e+00	0.2442
550	AUP1	SYSMH5	Human	Oral cavity	OSCC	3.94e-19	8.22e-01	0.0647
550	AUP1	SYSMH6	Human	Oral cavity	OSCC	2.81e-14	6.75e-01	0.1275
550	AUP1	P5_S10_cSCC	Human	Skin	cSCC	2.76e-08	1.44e-01	-0.299
550	AUP1	P1_cSCC	Human	Skin	cSCC	4.29e-30	1.25e+00	0.0292
550	AUP1	P2_cSCC	Human	Skin	cSCC	1.70e-13	6.96e-01	-0.024
550	AUP1	P4_cSCC	Human	Skin	cSCC	2.64e-31	8.96e-01	-0.00290000000000005
550	AUP1	P10_cSCC	Human	Skin	cSCC	9.03e-40	1.27e+00	0.1017
550	AUP1	cSCC_p8	Human	Skin	cSCC	4.89e-08	1.41e-01	-0.1971
550	AUP1	cSCC_p9	Human	Skin	cSCC	4.07e-08	1.23e-01	-0.1991
550	AUP1	male-WTA	Human	Thyroid	PTC	1.61e-35	1.87e-01	0.1037

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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:0010498	Colorectum	AD	proteasomal protein catabolic process	174/3918	490/18723	3.18e-14	7.66e-12	174
GO:0043161	Colorectum	AD	proteasome-mediated ubiquitin-dependent protein catabolic process	141/3918	412/18723	1.77e-10	1.68e-08	141
GO:0016236	Colorectum	AD	macroautophagy	103/3918	291/18723	6.76e-09	4.15e-07	103
GO:0034976	Colorectum	AD	response to endoplasmic reticulum stress	90/3918	256/18723	8.48e-08	4.28e-06	90
GO:0061912	Colorectum	AD	selective autophagy	29/3918	68/18723	4.20e-05	7.39e-04	29
GO:0035966	Colorectum	AD	response to topologically incorrect protein	54/3918	159/18723	8.85e-05	1.36e-03	54
GO:0035967	Colorectum	AD	cellular response to topologically incorrect protein	42/3918	116/18723	1.04e-04	1.56e-03	42
GO:0006515	Colorectum	AD	protein quality control for misfolded or incompletely synthesized proteins	14/3918	28/18723	6.01e-04	6.33e-03	14
GO:0010876	Colorectum	AD	lipid localization	120/3918	448/18723	1.59e-03	1.33e-02	120
GO:0071712	Colorectum	AD	ER-associated misfolded protein catabolic process	7/3918	12/18723	5.09e-03	3.38e-02	7
GO:0036503	Colorectum	AD	ERAD pathway	34/3918	107/18723	5.57e-03	3.63e-02	34
GO:00104981	Colorectum	SER	proteasomal protein catabolic process	132/2897	490/18723	3.08e-11	5.55e-09	132
GO:00349761	Colorectum	SER	response to endoplasmic reticulum stress	74/2897	256/18723	3.01e-08	2.05e-06	74
GO:00431611	Colorectum	SER	proteasome-mediated ubiquitin-dependent protein catabolic process	105/2897	412/18723	7.48e-08	4.70e-06	105
GO:00162361	Colorectum	SER	macroautophagy	79/2897	291/18723	1.97e-07	1.10e-05	79
GO:00359661	Colorectum	SER	response to topologically incorrect protein	46/2897	159/18723	1.14e-05	3.63e-04	46
GO:00359671	Colorectum	SER	cellular response to topologically incorrect protein	36/2897	116/18723	1.88e-05	5.51e-04	36
GO:00619121	Colorectum	SER	selective autophagy	24/2897	68/18723	4.60e-05	1.15e-03	24
GO:00065151	Colorectum	SER	protein quality control for misfolded or incompletely synthesized proteins	12/2897	28/18723	4.92e-04	7.02e-03	12
GO:0030970	Colorectum	SER	retrograde protein transport, ER to cytosol	12/2897	29/18723	7.22e-04	9.44e-03	12

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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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