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: SNX17

Gene summary for SNX17

Gene summary.

Gene information	Species	Human
	Gene symbol	SNX17
	Gene ID	9784
	Gene name	sorting nexin 17
	Gene Alias	SNX17
	Cytomap	2p23.3
	Gene Type	protein-coding
	GO ID	GO:0001568
	UniProtAcc	B4DTB8

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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
9784	SNX17	HTA11_99999974143_84620	Human	Colorectum	MSS	5.49e-18	4.39e-01	0.3005
9784	SNX17	LZE2T	Human	Esophagus	ESCC	4.77e-08	7.49e-01	0.082
9784	SNX17	LZE4T	Human	Esophagus	ESCC	2.50e-23	7.67e-01	0.0811
9784	SNX17	LZE7T	Human	Esophagus	ESCC	4.38e-06	4.62e-01	0.0667
9784	SNX17	LZE8T	Human	Esophagus	ESCC	1.48e-13	4.58e-01	0.067
9784	SNX17	LZE20T	Human	Esophagus	ESCC	1.76e-02	2.65e-01	0.0662
9784	SNX17	LZE22D1	Human	Esophagus	HGIN	1.90e-07	2.82e-01	0.0595
9784	SNX17	LZE22T	Human	Esophagus	ESCC	1.03e-04	6.33e-01	0.068
9784	SNX17	LZE24T	Human	Esophagus	ESCC	2.42e-26	7.41e-01	0.0596
9784	SNX17	LZE21T	Human	Esophagus	ESCC	4.39e-09	6.63e-01	0.0655
9784	SNX17	LZE6T	Human	Esophagus	ESCC	8.80e-16	8.74e-01	0.0845
9784	SNX17	P1T-E	Human	Esophagus	ESCC	6.24e-07	6.06e-01	0.0875
9784	SNX17	P2T-E	Human	Esophagus	ESCC	1.30e-80	1.47e+00	0.1177
9784	SNX17	P4T-E	Human	Esophagus	ESCC	5.06e-43	1.04e+00	0.1323
9784	SNX17	P5T-E	Human	Esophagus	ESCC	1.76e-20	5.16e-01	0.1327
9784	SNX17	P8T-E	Human	Esophagus	ESCC	6.21e-48	9.00e-01	0.0889
9784	SNX17	P9T-E	Human	Esophagus	ESCC	8.82e-29	7.06e-01	0.1131
9784	SNX17	P10T-E	Human	Esophagus	ESCC	2.14e-43	9.26e-01	0.116
9784	SNX17	P11T-E	Human	Esophagus	ESCC	2.91e-28	1.28e+00	0.1426
9784	SNX17	P12T-E	Human	Esophagus	ESCC	7.59e-47	9.65e-01	0.1122

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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
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:0016197	Colorectum	AD	endosomal transport	90/3918	230/18723	1.88e-10	1.73e-08	90
GO:0098876	Colorectum	AD	vesicle-mediated transport to the plasma membrane	57/3918	136/18723	2.30e-08	1.27e-06	57
GO:1901361	Colorectum	AD	organic cyclic compound catabolic process	153/3918	495/18723	8.23e-08	4.18e-06	153
GO:0044282	Colorectum	AD	small molecule catabolic process	118/3918	376/18723	1.05e-06	3.55e-05	118
GO:0006066	Colorectum	AD	alcohol metabolic process	106/3918	353/18723	3.02e-05	5.57e-04	106
GO:0016042	Colorectum	AD	lipid catabolic process	97/3918	320/18723	4.31e-05	7.56e-04	97
GO:0006898	Colorectum	AD	receptor-mediated endocytosis	76/3918	244/18723	1.07e-04	1.59e-03	76
GO:0030100	Colorectum	AD	regulation of endocytosis	67/3918	211/18723	1.42e-04	2.01e-03	67
GO:0032456	Colorectum	AD	endocytic recycling	28/3918	73/18723	4.87e-04	5.30e-03	28
GO:0046164	Colorectum	AD	alcohol catabolic process	20/3918	55/18723	6.03e-03	3.78e-02	20
GO:0008202	Colorectum	AD	steroid metabolic process	85/3918	319/18723	8.07e-03	4.75e-02	85
GO:00161971	Colorectum	SER	endosomal transport	61/2897	230/18723	1.03e-05	3.35e-04	61
GO:00160421	Colorectum	SER	lipid catabolic process	77/2897	320/18723	3.52e-05	9.18e-04	77
GO:00442821	Colorectum	SER	small molecule catabolic process	87/2897	376/18723	5.31e-05	1.27e-03	87
GO:00988761	Colorectum	SER	vesicle-mediated transport to the plasma membrane	37/2897	136/18723	3.08e-04	5.00e-03	37
GO:00060661	Colorectum	SER	alcohol metabolic process	79/2897	353/18723	3.50e-04	5.50e-03	79
GO:19013611	Colorectum	SER	organic cyclic compound catabolic process	104/2897	495/18723	5.46e-04	7.63e-03	104
GO:00461641	Colorectum	SER	alcohol catabolic process	17/2897	55/18723	3.00e-03	2.65e-02	17
GO:00301001	Colorectum	SER	regulation of endocytosis	48/2897	211/18723	3.29e-03	2.82e-02	48
GO:19013612	Colorectum	MSS	organic cyclic compound catabolic process	148/3467	495/18723	3.47e-10	3.18e-08	148

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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

SNX17

SNV

Missense_Mutation

rs756756686

c.827N>T

p.Ala276Val

p.A276V

Q15036

protein_coding

deleterious(0)

benign(0.043)

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SNX17

SNV

Missense_Mutation

rs747689756

c.708N>T

p.Trp236Cys

p.W236C

Q15036

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNX17

SNV

Missense_Mutation

c.1034N>A

p.Arg345His

p.R345H

Q15036

protein_coding

tolerated(0.1)

benign(0.006)

TCGA-AQ-A1H3-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

SNX17

SNV

Missense_Mutation

novel

c.954N>A

p.Met318Ile

p.M318I

Q15036

protein_coding

tolerated(0.24)

benign(0.134)

TCGA-B6-A3ZX-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

SNX17

SNV

Missense_Mutation

c.1054N>A

p.Tyr352Asn

p.Y352N

Q15036

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-E2-A1LL-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

docetaxel

SNX17

SNV

Missense_Mutation

novel

c.968T>G

p.Val323Gly

p.V323G

Q15036

protein_coding

deleterious(0)

possibly_damaging(0.536)

TCGA-OL-A6VO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

SNX17

insertion

In_Frame_Ins

novel

c.281_282insTGGTTTTCTGTCCAGTCTTACTGCTCTAGTAGCCTTTAC

p.Ser94_Ser95insGlyPheLeuSerSerLeuThrAlaLeuValAlaPheThr

p.S94_S95insGFLSSLTALVAFT

Q15036

protein_coding

TCGA-A2-A0D0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

SNX17

insertion

Frame_Shift_Ins

novel

c.1390_1391insACCTGAT

p.Gly464AspfsTer7

p.G464Dfs*7

Q15036

protein_coding

TCGA-AQ-A04J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

SNX17

insertion

Frame_Shift_Ins

novel

c.1392_1393insCACCCGGGAGTCTATGGTCAAACTCTCAGTG

p.Ile465HisfsTer14

p.I465Hfs*14

Q15036

protein_coding

TCGA-AQ-A04J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

SNX17

insertion

Nonsense_Mutation

novel

c.142_143insCCAGATCTTAAACTCTATTTAACTCA

p.Arg48ProfsTer4

p.R48Pfs*4

Q15036

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

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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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