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: SHOC2

Gene summary for SHOC2

Gene summary.

Gene information	Species	Human
	Gene symbol	SHOC2
	Gene ID	8036
	Gene name	SHOC2 leucine rich repeat scaffold protein
	Gene Alias	NSLH1
	Cytomap	10q25.2
	Gene Type	protein-coding
	GO ID	GO:0007154
	UniProtAcc	Q9UQ13

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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
8036	SHOC2	LZE4T	Human	Esophagus	ESCC	2.16e-15	4.32e-01	0.0811
8036	SHOC2	LZE5T	Human	Esophagus	ESCC	2.08e-08	3.33e-01	0.0514
8036	SHOC2	LZE7T	Human	Esophagus	ESCC	5.02e-05	1.67e-01	0.0667
8036	SHOC2	LZE8T	Human	Esophagus	ESCC	3.19e-08	1.72e-01	0.067
8036	SHOC2	LZE20T	Human	Esophagus	ESCC	2.14e-03	1.68e-01	0.0662
8036	SHOC2	LZE22T	Human	Esophagus	ESCC	5.31e-04	2.26e-01	0.068
8036	SHOC2	LZE24T	Human	Esophagus	ESCC	4.54e-16	4.35e-01	0.0596
8036	SHOC2	LZE21T	Human	Esophagus	ESCC	2.87e-04	1.95e-01	0.0655
8036	SHOC2	LZE6T	Human	Esophagus	ESCC	1.66e-02	1.38e-01	0.0845
8036	SHOC2	P1T-E	Human	Esophagus	ESCC	6.42e-08	4.58e-01	0.0875
8036	SHOC2	P2T-E	Human	Esophagus	ESCC	6.12e-17	2.27e-01	0.1177
8036	SHOC2	P4T-E	Human	Esophagus	ESCC	1.38e-23	4.15e-01	0.1323
8036	SHOC2	P5T-E	Human	Esophagus	ESCC	5.97e-25	4.33e-01	0.1327
8036	SHOC2	P8T-E	Human	Esophagus	ESCC	6.86e-29	4.86e-01	0.0889
8036	SHOC2	P9T-E	Human	Esophagus	ESCC	1.76e-13	3.08e-01	0.1131
8036	SHOC2	P10T-E	Human	Esophagus	ESCC	6.06e-10	1.37e-01	0.116
8036	SHOC2	P11T-E	Human	Esophagus	ESCC	2.06e-20	5.70e-01	0.1426
8036	SHOC2	P12T-E	Human	Esophagus	ESCC	1.23e-26	4.54e-01	0.1122
8036	SHOC2	P15T-E	Human	Esophagus	ESCC	1.03e-14	2.59e-01	0.1149
8036	SHOC2	P16T-E	Human	Esophagus	ESCC	6.24e-19	2.56e-01	0.1153

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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:000726510	Esophagus	ESCC	Ras protein signal transduction	201/8552	337/18723	1.44e-07	2.30e-06	201
GO:00465789	Esophagus	ESCC	regulation of Ras protein signal transduction	106/8552	189/18723	2.49e-03	1.08e-02	106
GO:005105610	Esophagus	ESCC	regulation of small GTPase mediated signal transduction	157/8552	302/18723	1.55e-02	4.98e-02	157
GO:000726511	Liver	Cirrhotic	Ras protein signal transduction	119/4634	337/18723	8.16e-06	1.22e-04	119
GO:000726521	Liver	HCC	Ras protein signal transduction	187/7958	337/18723	8.89e-07	1.35e-05	187
GO:004657811	Liver	HCC	regulation of Ras protein signal transduction	100/7958	189/18723	2.42e-03	1.18e-02	100
GO:00072659	Oral cavity	OSCC	Ras protein signal transduction	185/7305	337/18723	1.95e-09	4.60e-08	185
GO:00465788	Oral cavity	OSCC	regulation of Ras protein signal transduction	90/7305	189/18723	9.58e-03	3.40e-02	90
GO:000726522	Oral cavity	EOLP	Ras protein signal transduction	74/2218	337/18723	8.76e-08	3.09e-06	74
GO:00510569	Oral cavity	EOLP	regulation of small GTPase mediated signal transduction	51/2218	302/18723	5.67e-03	2.92e-02	51
GO:000726531	Oral cavity	NEOLP	Ras protein signal transduction	71/2005	337/18723	1.60e-08	7.27e-07	71
GO:004657815	Oral cavity	NEOLP	regulation of Ras protein signal transduction	36/2005	189/18723	4.30e-04	3.92e-03	36
GO:005105614	Oral cavity	NEOLP	regulation of small GTPase mediated signal transduction	49/2005	302/18723	2.04e-03	1.36e-02	49
GO:000726523	Skin	cSCC	Ras protein signal transduction	132/4864	337/18723	6.17e-08	1.57e-06	132
GO:000726519	Thyroid	PTC	Ras protein signal transduction	162/5968	337/18723	3.16e-10	1.02e-08	162
GO:005105617	Thyroid	PTC	regulation of small GTPase mediated signal transduction	132/5968	302/18723	9.26e-06	1.04e-04	132
GO:004657817	Thyroid	PTC	regulation of Ras protein signal transduction	88/5968	189/18723	1.62e-05	1.70e-04	88
GO:000726524	Thyroid	ATC	Ras protein signal transduction	172/6293	337/18723	2.25e-11	7.96e-10	172
GO:005105618	Thyroid	ATC	regulation of small GTPase mediated signal transduction	141/6293	302/18723	1.43e-06	1.77e-05	141
GO:004657818	Thyroid	ATC	regulation of Ras protein signal transduction	94/6293	189/18723	3.12e-06	3.55e-05	94

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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

SHOC2

SNV

Missense_Mutation

c.1522C>T

p.His508Tyr

p.H508Y

Q9UQ13

protein_coding

tolerated(1)

benign(0.003)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SHOC2

SNV

Missense_Mutation

novel

c.539N>C

p.Lys180Thr

p.K180T

Q9UQ13

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SHOC2

SNV

Missense_Mutation

novel

c.1677N>T

p.Gln559His

p.Q559H

Q9UQ13

protein_coding

deleterious(0.01)

benign(0.012)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SHOC2

SNV

Missense_Mutation

novel

c.692N>T

p.Pro231Leu

p.P231L

Q9UQ13

protein_coding

deleterious(0)

probably_damaging(0.985)

TCGA-B6-A0RG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SHOC2

SNV

Missense_Mutation

novel

c.1064N>G

p.Ser355Cys

p.S355C

Q9UQ13

protein_coding

tolerated(0.26)

benign(0)

TCGA-C8-A8HQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SHOC2

SNV

Missense_Mutation

c.788T>C

p.Ile263Thr

p.I263T

Q9UQ13

protein_coding

deleterious(0)

possibly_damaging(0.534)

TCGA-E9-A22G-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SHOC2

insertion

Frame_Shift_Ins

novel

c.129dupT

p.Lys44Ter

p.K44*

Q9UQ13

protein_coding

TCGA-A8-A08J-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

SHOC2

SNV

Missense_Mutation

novel

c.863G>A

p.Arg288His

p.R288H

Q9UQ13

protein_coding

deleterious(0.03)

possibly_damaging(0.9)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SHOC2

SNV

Missense_Mutation

novel

c.1509G>T

p.Glu503Asp

p.E503D

Q9UQ13

protein_coding

deleterious(0.05)

possibly_damaging(0.469)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SHOC2

SNV

Missense_Mutation

novel

c.1638N>A

p.Met546Ile

p.M546I

Q9UQ13

protein_coding

deleterious(0.01)

possibly_damaging(0.576)

TCGA-DG-A2KJ-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

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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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