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: SQSTM1

Gene summary for SQSTM1

Gene summary.

Gene information	Species	Human
	Gene symbol	SQSTM1
	Gene ID	8878
	Gene name	sequestosome 1
	Gene Alias	A170
	Cytomap	5q35.3
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q13501

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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
8878	SQSTM1	GSM4909281	Human	Breast	IDC	2.98e-09	-3.71e-01	0.21
8878	SQSTM1	GSM4909282	Human	Breast	IDC	1.03e-09	-5.45e-01	-0.0288
8878	SQSTM1	GSM4909285	Human	Breast	IDC	8.26e-12	-4.31e-01	0.21
8878	SQSTM1	GSM4909286	Human	Breast	IDC	1.31e-38	-8.69e-01	0.1081
8878	SQSTM1	GSM4909290	Human	Breast	IDC	5.33e-05	-3.99e-01	0.2096
8878	SQSTM1	GSM4909292	Human	Breast	IDC	2.02e-16	8.07e-01	0.1236
8878	SQSTM1	GSM4909293	Human	Breast	IDC	1.95e-05	-1.94e-01	0.1581
8878	SQSTM1	GSM4909294	Human	Breast	IDC	1.94e-04	-3.47e-01	0.2022
8878	SQSTM1	GSM4909296	Human	Breast	IDC	1.10e-23	-7.09e-01	0.1524
8878	SQSTM1	GSM4909297	Human	Breast	IDC	1.45e-19	-5.98e-01	0.1517
8878	SQSTM1	GSM4909298	Human	Breast	IDC	3.61e-07	-1.47e-01	0.1551
8878	SQSTM1	GSM4909301	Human	Breast	IDC	1.73e-05	-4.00e-01	0.1577
8878	SQSTM1	GSM4909304	Human	Breast	IDC	1.56e-07	-3.79e-01	0.1636
8878	SQSTM1	GSM4909306	Human	Breast	IDC	2.03e-03	-2.90e-01	0.1564
8878	SQSTM1	GSM4909308	Human	Breast	IDC	3.95e-08	2.23e-01	0.158
8878	SQSTM1	GSM4909311	Human	Breast	IDC	1.41e-37	-6.95e-01	0.1534
8878	SQSTM1	GSM4909312	Human	Breast	IDC	5.07e-18	-5.93e-01	0.1552
8878	SQSTM1	GSM4909317	Human	Breast	IDC	3.50e-02	-6.08e-02	0.1355
8878	SQSTM1	GSM4909319	Human	Breast	IDC	6.36e-37	-2.83e-01	0.1563
8878	SQSTM1	GSM4909320	Human	Breast	IDC	7.42e-06	-5.58e-01	0.1575

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
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
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:190332110	Cervix	CC	negative regulation of protein modification by small protein conjugation or removal	29/2311	95/18723	2.15e-06	6.55e-05	29
GO:19030788	Cervix	CC	positive regulation of protein localization to plasma membrane	21/2311	62/18723	8.91e-06	2.03e-04	21
GO:00465785	Cervix	CC	regulation of Ras protein signal transduction	44/2311	189/18723	2.05e-05	3.73e-04	44
GO:19054778	Cervix	CC	positive regulation of protein localization to membrane	29/2311	106/18723	2.29e-05	4.01e-04	29
GO:00431228	Cervix	CC	regulation of I-kappaB kinase/NF-kappaB signaling	53/2311	249/18723	4.50e-05	6.87e-04	53
GO:002241110	Cervix	CC	cellular component disassembly	83/2311	443/18723	6.04e-05	8.68e-04	83
GO:19030768	Cervix	CC	regulation of protein localization to plasma membrane	27/2311	104/18723	1.15e-04	1.44e-03	27
GO:00108218	Cervix	CC	regulation of mitochondrion organization	34/2311	144/18723	1.27e-04	1.58e-03	34
GO:00162367	Cervix	CC	macroautophagy	58/2311	291/18723	1.40e-04	1.70e-03	58
GO:00161977	Cervix	CC	endosomal transport	48/2311	230/18723	1.65e-04	1.97e-03	48
GO:00072497	Cervix	CC	I-kappaB kinase/NF-kappaB signaling	56/2311	281/18723	1.81e-04	2.12e-03	56
GO:19043758	Cervix	CC	regulation of protein localization to cell periphery	30/2311	125/18723	2.28e-04	2.56e-03	30
GO:00004227	Cervix	CC	autophagy of mitochondrion	21/2311	81/18723	6.47e-04	6.02e-03	21
GO:00617267	Cervix	CC	mitochondrion disassembly	21/2311	81/18723	6.47e-04	6.02e-03	21
GO:19054758	Cervix	CC	regulation of protein localization to membrane	36/2311	175/18723	1.33e-03	1.05e-02	36
GO:00160506	Cervix	CC	vesicle organization	54/2311	300/18723	2.71e-03	1.85e-02	54
GO:003139625	Cervix	N_HPV	regulation of protein ubiquitination	24/534	210/18723	8.06e-09	1.60e-06	24
GO:190332025	Cervix	N_HPV	regulation of protein modification by small protein conjugation or removal	25/534	242/18723	3.05e-08	3.66e-06	25
GO:003139725	Cervix	N_HPV	negative regulation of protein ubiquitination	13/534	83/18723	6.09e-07	3.75e-05	13
GO:190332125	Cervix	N_HPV	negative regulation of protein modification by small protein conjugation or removal	13/534	95/18723	2.94e-06	1.26e-04	13

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0501416	Breast	Precancer	Amyotrophic lateral sclerosis	98/684	364/8465	2.13e-28	8.41e-27	6.44e-27	98
hsa0502216	Breast	Precancer	Pathways of neurodegeneration - multiple diseases	112/684	476/8465	6.96e-27	2.44e-25	1.87e-25	112
hsa0513118	Breast	Precancer	Shigellosis	44/684	247/8465	3.91e-07	6.86e-06	5.26e-06	44
hsa0541818	Breast	Precancer	Fluid shear stress and atherosclerosis	28/684	139/8465	4.74e-06	6.00e-05	4.59e-05	28
hsa042189	Breast	Precancer	Cellular senescence	29/684	156/8465	1.66e-05	1.69e-04	1.30e-04	29
hsa0501417	Breast	Precancer	Amyotrophic lateral sclerosis	98/684	364/8465	2.13e-28	8.41e-27	6.44e-27	98
hsa0502217	Breast	Precancer	Pathways of neurodegeneration - multiple diseases	112/684	476/8465	6.96e-27	2.44e-25	1.87e-25	112
hsa0513119	Breast	Precancer	Shigellosis	44/684	247/8465	3.91e-07	6.86e-06	5.26e-06	44
hsa0541819	Breast	Precancer	Fluid shear stress and atherosclerosis	28/684	139/8465	4.74e-06	6.00e-05	4.59e-05	28
hsa0421814	Breast	Precancer	Cellular senescence	29/684	156/8465	1.66e-05	1.69e-04	1.30e-04	29
hsa0501423	Breast	IDC	Amyotrophic lateral sclerosis	102/867	364/8465	1.29e-22	5.22e-21	3.91e-21	102
hsa0502223	Breast	IDC	Pathways of neurodegeneration - multiple diseases	116/867	476/8465	3.63e-20	1.18e-18	8.82e-19	116
hsa0541824	Breast	IDC	Fluid shear stress and atherosclerosis	34/867	139/8465	9.41e-07	1.61e-05	1.20e-05	34
hsa0421824	Breast	IDC	Cellular senescence	35/867	156/8465	5.49e-06	7.43e-05	5.56e-05	35
hsa0513124	Breast	IDC	Shigellosis	47/867	247/8465	1.78e-05	2.00e-04	1.49e-04	47
hsa0413723	Breast	IDC	Mitophagy - animal	17/867	72/8465	7.61e-04	6.04e-03	4.52e-03	17
hsa0501433	Breast	IDC	Amyotrophic lateral sclerosis	102/867	364/8465	1.29e-22	5.22e-21	3.91e-21	102
hsa0502233	Breast	IDC	Pathways of neurodegeneration - multiple diseases	116/867	476/8465	3.63e-20	1.18e-18	8.82e-19	116
hsa0541834	Breast	IDC	Fluid shear stress and atherosclerosis	34/867	139/8465	9.41e-07	1.61e-05	1.20e-05	34
hsa0421834	Breast	IDC	Cellular senescence	35/867	156/8465	5.49e-06	7.43e-05	5.56e-05	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

SQSTM1

SNV

Missense_Mutation

novel

c.1260N>T

p.Lys420Asn

p.K420N

Q13501

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SQSTM1

SNV

Missense_Mutation

novel

c.465G>T

p.Glu155Asp

p.E155D

Q13501

protein_coding

deleterious(0.01)

probably_damaging(0.952)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SQSTM1

SNV

Missense_Mutation

c.494N>G

p.Lys165Arg

p.K165R

Q13501

protein_coding

tolerated(0.15)

benign(0.425)

TCGA-B6-A0IJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SQSTM1

SNV

Missense_Mutation

rs772889843

c.1043N>T

p.Pro348Leu

p.P348L

Q13501

protein_coding

deleterious(0)

probably_damaging(0.981)

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SQSTM1

deletion

Frame_Shift_Del

novel

c.321_328delNNNNNNNN

p.Asp108ProfsTer42

p.D108Pfs*42

Q13501

protein_coding

TCGA-AN-A03X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SQSTM1

insertion

Nonsense_Mutation

novel

c.1211_1212insTGAGCACTGAGTGAACCAGACTCCGTCTGCAATCCC

p.Met404delinsIleGluHisTerValAsnGlnThrProSerAlaIlePro

p.M404delinsIEH*VNQTPSAIP

Q13501

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

SQSTM1

SNV

Missense_Mutation

c.1099C>G

p.Leu367Val

p.L367V

Q13501

protein_coding

tolerated(0.11)

benign(0.007)

TCGA-FU-A5XV-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

SQSTM1

SNV

Missense_Mutation

c.850T>G

p.Ser284Ala

p.S284A

Q13501

protein_coding

tolerated(0.42)

benign(0)

TCGA-AA-3492-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

SQSTM1

SNV

Missense_Mutation

rs758625124

c.481N>T

p.Arg161Trp

p.R161W

Q13501

protein_coding

deleterious(0)

possibly_damaging(0.67)

TCGA-AA-3819-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

SQSTM1

SNV

Missense_Mutation

rs200551825

c.1178N>A

p.Arg393Gln

p.R393Q

Q13501

protein_coding

deleterious(0.01)

possibly_damaging(0.56)

TCGA-WS-AB45-01

Colorectum

colon adenocarcinoma

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
8878	SQSTM1	SERINE THREONINE KINASE		IMX-942	DUSQUETIDE

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