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: SHKBP1

Gene summary for SHKBP1

Gene summary.

Gene information	Species	Human
	Gene symbol	SHKBP1
	Gene ID	92799
	Gene name	SH3KBP1 binding protein 1
	Gene Alias	PP203
	Cytomap	19q13.2
	Gene Type	protein-coding
	GO ID	GO:0007154
	UniProtAcc	Q8TBC3

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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
92799	SHKBP1	LZE2T	Human	Esophagus	ESCC	2.43e-04	4.67e-01	0.082
92799	SHKBP1	LZE4T	Human	Esophagus	ESCC	5.48e-12	3.32e-01	0.0811
92799	SHKBP1	LZE7T	Human	Esophagus	ESCC	1.01e-18	5.85e-01	0.0667
92799	SHKBP1	LZE8T	Human	Esophagus	ESCC	6.21e-13	3.95e-01	0.067
92799	SHKBP1	LZE20T	Human	Esophagus	ESCC	3.43e-06	2.03e-01	0.0662
92799	SHKBP1	LZE22T	Human	Esophagus	ESCC	3.27e-08	5.60e-01	0.068
92799	SHKBP1	LZE24T	Human	Esophagus	ESCC	2.21e-33	7.49e-01	0.0596
92799	SHKBP1	LZE6T	Human	Esophagus	ESCC	6.63e-16	5.91e-01	0.0845
92799	SHKBP1	P1T-E	Human	Esophagus	ESCC	4.42e-15	7.41e-01	0.0875
92799	SHKBP1	P2T-E	Human	Esophagus	ESCC	4.32e-25	4.52e-01	0.1177
92799	SHKBP1	P4T-E	Human	Esophagus	ESCC	6.22e-29	5.07e-01	0.1323
92799	SHKBP1	P5T-E	Human	Esophagus	ESCC	1.54e-23	4.67e-01	0.1327
92799	SHKBP1	P8T-E	Human	Esophagus	ESCC	5.31e-68	1.30e+00	0.0889
92799	SHKBP1	P9T-E	Human	Esophagus	ESCC	1.18e-17	2.67e-01	0.1131
92799	SHKBP1	P10T-E	Human	Esophagus	ESCC	2.81e-42	7.14e-01	0.116
92799	SHKBP1	P11T-E	Human	Esophagus	ESCC	4.63e-26	7.10e-01	0.1426
92799	SHKBP1	P12T-E	Human	Esophagus	ESCC	7.61e-31	5.23e-01	0.1122
92799	SHKBP1	P15T-E	Human	Esophagus	ESCC	1.37e-38	7.53e-01	0.1149
92799	SHKBP1	P16T-E	Human	Esophagus	ESCC	3.26e-14	1.89e-01	0.1153
92799	SHKBP1	P17T-E	Human	Esophagus	ESCC	1.30e-21	8.47e-01	0.1278

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:003812718	Esophagus	ESCC	ERBB signaling pathway	82/8552	121/18723	7.23e-07	9.40e-06	82
GO:000717318	Esophagus	ESCC	epidermal growth factor receptor signaling pathway	73/8552	108/18723	3.36e-06	3.73e-05	73
GO:190118413	Esophagus	ESCC	regulation of ERBB signaling pathway	54/8552	79/18723	3.81e-05	3.08e-04	54
GO:00420588	Esophagus	ESCC	regulation of epidermal growth factor receptor signaling pathway	50/8552	73/18723	6.75e-05	5.12e-04	50
GO:00512592	Esophagus	ESCC	protein complex oligomerization	130/8552	238/18723	3.29e-03	1.36e-02	130
GO:003812711	Liver	Cirrhotic	ERBB signaling pathway	46/4634	121/18723	8.08e-04	5.93e-03	46
GO:000717311	Liver	Cirrhotic	epidermal growth factor receptor signaling pathway	39/4634	108/18723	5.49e-03	2.79e-02	39
GO:003812721	Liver	HCC	ERBB signaling pathway	73/7958	121/18723	5.65e-05	5.26e-04	73
GO:000717321	Liver	HCC	epidermal growth factor receptor signaling pathway	65/7958	108/18723	1.56e-04	1.25e-03	65
GO:19011844	Liver	HCC	regulation of ERBB signaling pathway	47/7958	79/18723	1.71e-03	8.91e-03	47
GO:00420584	Liver	HCC	regulation of epidermal growth factor receptor signaling pathway	43/7958	73/18723	3.43e-03	1.55e-02	43
GO:003812715	Oral cavity	OSCC	ERBB signaling pathway	76/7305	121/18723	9.59e-08	1.66e-06	76
GO:000717315	Oral cavity	OSCC	epidermal growth factor receptor signaling pathway	67/7305	108/18723	1.04e-06	1.40e-05	67
GO:19011847	Oral cavity	OSCC	regulation of ERBB signaling pathway	50/7305	79/18723	1.06e-05	1.12e-04	50
GO:00420587	Oral cavity	OSCC	regulation of epidermal growth factor receptor signaling pathway	46/7305	73/18723	2.80e-05	2.59e-04	46
GO:0051259	Oral cavity	OSCC	protein complex oligomerization	121/7305	238/18723	1.29e-04	9.21e-04	121
GO:00512591	Oral cavity	LP	protein complex oligomerization	85/4623	238/18723	8.81e-05	1.11e-03	85
GO:190118412	Oral cavity	LP	regulation of ERBB signaling pathway	30/4623	79/18723	5.97e-03	3.54e-02	30
GO:003812716	Oral cavity	LP	ERBB signaling pathway	42/4623	121/18723	8.53e-03	4.61e-02	42
GO:003812724	Skin	cSCC	ERBB signaling pathway	55/4864	121/18723	2.77e-06	4.38e-05	55

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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

SHKBP1

SNV

Missense_Mutation

rs201616547

c.1588N>T

p.Arg530Trp

p.R530W

Q8TBC3

protein_coding

deleterious(0)

probably_damaging(0.985)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

SHKBP1

SNV

Missense_Mutation

c.1871N>T

p.Ser624Leu

p.S624L

Q8TBC3

protein_coding

deleterious_low_confidence(0.04)

benign(0.054)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SHKBP1

SNV

Missense_Mutation

rs761519156

c.1242G>T

p.Glu414Asp

p.E414D

Q8TBC3

protein_coding

deleterious(0)

possibly_damaging(0.584)

TCGA-E2-A15I-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

SHKBP1

SNV

Missense_Mutation

novel

c.1651N>A

p.Glu551Lys

p.E551K

Q8TBC3

protein_coding

deleterious(0)

probably_damaging(0.972)

TCGA-C5-A7CK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SHKBP1

SNV

Missense_Mutation

c.1437N>G

p.Ile479Met

p.I479M

Q8TBC3

protein_coding

deleterious(0.01)

probably_damaging(0.986)

TCGA-UC-A7PF-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SHKBP1

SNV

Missense_Mutation

novel

c.177G>C

p.Glu59Asp

p.E59D

Q8TBC3

protein_coding

tolerated(0.06)

probably_damaging(0.983)

TCGA-ZJ-AAXB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SHKBP1

SNV

Missense_Mutation

c.1069N>T

p.Arg357Cys

p.R357C

Q8TBC3

protein_coding

deleterious(0)

possibly_damaging(0.732)

TCGA-A6-2686-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

SHKBP1

SNV

Missense_Mutation

c.919G>T

p.Gly307Trp

p.G307W

Q8TBC3

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AA-3833-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

SHKBP1

SNV

Missense_Mutation

rs750766482

c.2014C>T

p.Arg672Trp

p.R672W

Q8TBC3

protein_coding

deleterious_low_confidence(0)

benign(0.336)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

SHKBP1

SNV

Missense_Mutation

novel

c.2001C>G

p.Cys667Trp

p.C667W

Q8TBC3

protein_coding

deleterious_low_confidence(0)

benign(0.286)

TCGA-AA-A022-01

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

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