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: PACS1

Gene summary for PACS1

Gene summary.

Gene information	Species	Human
	Gene symbol	PACS1
	Gene ID	55690
	Gene name	phosphofurin acidic cluster sorting protein 1
	Gene Alias	MRD17
	Cytomap	11q13.1-q13.2
	Gene Type	protein-coding
	GO ID	GO:0008104
	UniProtAcc	A0A024R5H6

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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
55690	PACS1	P27T-E	Human	Esophagus	ESCC	3.53e-10	6.53e-02	0.1055
55690	PACS1	P28T-E	Human	Esophagus	ESCC	3.64e-17	2.47e-01	0.1149
55690	PACS1	P30T-E	Human	Esophagus	ESCC	2.60e-07	2.30e-01	0.137
55690	PACS1	P31T-E	Human	Esophagus	ESCC	1.04e-14	1.93e-01	0.1251
55690	PACS1	P32T-E	Human	Esophagus	ESCC	1.94e-12	1.68e-01	0.1666
55690	PACS1	P36T-E	Human	Esophagus	ESCC	1.61e-07	2.28e-01	0.1187
55690	PACS1	P37T-E	Human	Esophagus	ESCC	5.03e-13	2.81e-01	0.1371
55690	PACS1	P38T-E	Human	Esophagus	ESCC	2.25e-05	2.04e-01	0.127
55690	PACS1	P39T-E	Human	Esophagus	ESCC	1.86e-04	7.49e-02	0.0894
55690	PACS1	P40T-E	Human	Esophagus	ESCC	3.82e-09	2.62e-01	0.109
55690	PACS1	P42T-E	Human	Esophagus	ESCC	3.68e-10	3.14e-01	0.1175
55690	PACS1	P44T-E	Human	Esophagus	ESCC	6.06e-04	5.49e-02	0.1096
55690	PACS1	P47T-E	Human	Esophagus	ESCC	9.95e-12	9.13e-02	0.1067
55690	PACS1	P48T-E	Human	Esophagus	ESCC	1.05e-12	1.30e-01	0.0959
55690	PACS1	P49T-E	Human	Esophagus	ESCC	1.08e-06	7.77e-01	0.1768
55690	PACS1	P52T-E	Human	Esophagus	ESCC	6.90e-12	1.62e-01	0.1555
55690	PACS1	P54T-E	Human	Esophagus	ESCC	6.83e-07	1.86e-01	0.0975
55690	PACS1	P56T-E	Human	Esophagus	ESCC	3.60e-04	4.66e-01	0.1613
55690	PACS1	P57T-E	Human	Esophagus	ESCC	2.68e-13	2.88e-01	0.0926
55690	PACS1	P61T-E	Human	Esophagus	ESCC	2.96e-04	2.21e-01	0.099

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
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
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:007265910	Cervix	CC	protein localization to plasma membrane	73/2311	284/18723	4.95e-10	6.73e-08	73
GO:19907788	Cervix	CC	protein localization to cell periphery	78/2311	333/18723	1.22e-08	9.73e-07	78
GO:007265914	Endometrium	AEH	protein localization to plasma membrane	63/2100	284/18723	7.58e-08	3.92e-06	63
GO:19907789	Endometrium	AEH	protein localization to cell periphery	68/2100	333/18723	6.38e-07	2.38e-05	68
GO:007265915	Endometrium	EEC	protein localization to plasma membrane	64/2168	284/18723	1.05e-07	5.05e-06	64
GO:199077814	Endometrium	EEC	protein localization to cell periphery	69/2168	333/18723	9.71e-07	3.31e-05	69
GO:0072659110	Esophagus	ESCC	protein localization to plasma membrane	193/8552	284/18723	1.95e-14	1.03e-12	193
GO:199077819	Esophagus	ESCC	protein localization to cell periphery	217/8552	333/18723	4.08e-13	1.88e-11	217
GO:00340676	Esophagus	ESCC	protein localization to Golgi apparatus	23/8552	29/18723	2.25e-04	1.40e-03	23
GO:007265921	Liver	HCC	protein localization to plasma membrane	177/7958	284/18723	1.02e-11	4.18e-10	177
GO:199077821	Liver	HCC	protein localization to cell periphery	200/7958	333/18723	6.07e-11	2.23e-09	200
GO:003406721	Liver	HCC	protein localization to Golgi apparatus	23/7958	29/18723	5.86e-05	5.38e-04	23
GO:00726598	Lung	IAC	protein localization to plasma membrane	60/2061	284/18723	4.74e-07	3.10e-05	60
GO:19907787	Lung	IAC	protein localization to cell periphery	66/2061	333/18723	1.44e-06	7.22e-05	66
GO:007265912	Lung	AIS	protein localization to plasma membrane	58/1849	284/18723	6.25e-08	7.14e-06	58
GO:199077812	Lung	AIS	protein localization to cell periphery	64/1849	333/18723	1.42e-07	1.48e-05	64
GO:007265918	Oral cavity	OSCC	protein localization to plasma membrane	169/7305	284/18723	1.69e-12	7.21e-11	169
GO:199077816	Oral cavity	OSCC	protein localization to cell periphery	190/7305	333/18723	1.46e-11	5.13e-10	190
GO:00340675	Oral cavity	OSCC	protein localization to Golgi apparatus	21/7305	29/18723	2.73e-04	1.73e-03	21
GO:007265919	Oral cavity	LP	protein localization to plasma membrane	119/4623	284/18723	1.11e-10	6.44e-09	119

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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

PACS1

SNV

Missense_Mutation

c.2369G>A

p.Arg790Gln

p.R790Q

Q6VY07

protein_coding

tolerated(0.07)

benign(0.024)

TCGA-A8-A06Q-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

PACS1

SNV

Missense_Mutation

rs398123009

c.607N>T

p.Arg203Trp

p.R203W

Q6VY07

protein_coding

deleterious(0)

probably_damaging(0.948)

TCGA-AC-A3QP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

PACS1

SNV

Missense_Mutation

c.1591N>T

p.Ser531Cys

p.S531C

Q6VY07

protein_coding

deleterious(0.04)

possibly_damaging(0.887)

TCGA-AN-A0AL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

PACS1

SNV

Missense_Mutation

c.2538G>C

p.Lys846Asn

p.K846N

Q6VY07

protein_coding

tolerated(0.07)

probably_damaging(0.998)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

PACS1

SNV

Missense_Mutation

c.1936N>A

p.Leu646Met

p.L646M

Q6VY07

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PACS1

SNV

Missense_Mutation

novel

c.1619N>A

p.Ser540Asn

p.S540N

Q6VY07

protein_coding

tolerated(0.38)

benign(0.056)

TCGA-E9-A5FL-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PACS1

insertion

Frame_Shift_Ins

novel

c.2183_2184insTCTCTGTGCACAGCCCCTCCACTCTGCCAGTTTT

p.Met729LeufsTer18

p.M729Lfs*18

Q6VY07

protein_coding

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

PACS1

deletion

Frame_Shift_Del

novel

c.2175delN

p.Ala726ProfsTer5

p.A726Pfs*5

Q6VY07

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

PACS1

SNV

Missense_Mutation

novel

c.1601N>T

p.Ser534Phe

p.S534F

Q6VY07

protein_coding

deleterious(0.04)

probably_damaging(0.994)

TCGA-C5-A7XC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PACS1

SNV

Missense_Mutation

c.725C>G

p.Ser242Cys

p.S242C

Q6VY07

protein_coding

deleterious(0)

possibly_damaging(0.707)

TCGA-EK-A2RC-01

Cervix

cervical & endocervical cancer

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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