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: SMC2

Gene summary for SMC2

Gene summary.

Gene information	Species	Human
	Gene symbol	SMC2
	Gene ID	10592
	Gene name	structural maintenance of chromosomes 2
	Gene Alias	CAP-E
	Cytomap	9q31.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	A0A024R158

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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
10592	SMC2	LZE2T	Human	Esophagus	ESCC	5.52e-10	1.08e+00	0.082
10592	SMC2	LZE4T	Human	Esophagus	ESCC	1.33e-04	3.30e-01	0.0811
10592	SMC2	LZE24T	Human	Esophagus	ESCC	4.91e-10	3.09e-01	0.0596
10592	SMC2	LZE6T	Human	Esophagus	ESCC	6.29e-05	3.68e-01	0.0845
10592	SMC2	P1T-E	Human	Esophagus	ESCC	3.33e-05	4.00e-01	0.0875
10592	SMC2	P2T-E	Human	Esophagus	ESCC	2.87e-41	1.03e+00	0.1177
10592	SMC2	P4T-E	Human	Esophagus	ESCC	3.39e-25	6.58e-01	0.1323
10592	SMC2	P5T-E	Human	Esophagus	ESCC	8.18e-28	7.01e-01	0.1327
10592	SMC2	P8T-E	Human	Esophagus	ESCC	6.56e-15	3.50e-01	0.0889
10592	SMC2	P9T-E	Human	Esophagus	ESCC	5.52e-08	3.29e-01	0.1131
10592	SMC2	P10T-E	Human	Esophagus	ESCC	1.04e-39	9.10e-01	0.116
10592	SMC2	P11T-E	Human	Esophagus	ESCC	8.02e-03	2.08e-01	0.1426
10592	SMC2	P12T-E	Human	Esophagus	ESCC	2.03e-09	2.29e-01	0.1122
10592	SMC2	P15T-E	Human	Esophagus	ESCC	3.18e-10	3.71e-01	0.1149
10592	SMC2	P16T-E	Human	Esophagus	ESCC	1.25e-19	4.17e-01	0.1153
10592	SMC2	P17T-E	Human	Esophagus	ESCC	2.19e-11	4.94e-01	0.1278
10592	SMC2	P19T-E	Human	Esophagus	ESCC	8.01e-03	4.20e-01	0.1662
10592	SMC2	P20T-E	Human	Esophagus	ESCC	2.23e-12	2.29e-01	0.1124
10592	SMC2	P21T-E	Human	Esophagus	ESCC	3.38e-37	8.47e-01	0.1617
10592	SMC2	P22T-E	Human	Esophagus	ESCC	2.22e-08	2.30e-01	0.1236

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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:00458629	Breast	Precancer	positive regulation of proteolysis	51/1080	372/18723	7.77e-09	5.70e-07	51
GO:00104989	Breast	Precancer	proteasomal protein catabolic process	58/1080	490/18723	1.54e-07	8.05e-06	58
GO:19033629	Breast	Precancer	regulation of cellular protein catabolic process	36/1080	255/18723	6.03e-07	2.55e-05	36
GO:00421769	Breast	Precancer	regulation of protein catabolic process	47/1080	391/18723	1.50e-06	5.58e-05	47
GO:19030509	Breast	Precancer	regulation of proteolysis involved in cellular protein catabolic process	31/1080	221/18723	4.10e-06	1.27e-04	31
GO:00611369	Breast	Precancer	regulation of proteasomal protein catabolic process	24/1080	187/18723	1.99e-04	3.14e-03	24
GO:00431619	Breast	Precancer	proteasome-mediated ubiquitin-dependent protein catabolic process	42/1080	412/18723	2.49e-04	3.72e-03	42
GO:00098969	Breast	Precancer	positive regulation of catabolic process	48/1080	492/18723	2.62e-04	3.84e-03	48
GO:00313319	Breast	Precancer	positive regulation of cellular catabolic process	43/1080	427/18723	2.75e-04	4.00e-03	43
GO:00016496	Breast	Precancer	osteoblast differentiation	27/1080	229/18723	3.35e-04	4.73e-03	27
GO:19033649	Breast	Precancer	positive regulation of cellular protein catabolic process	20/1080	155/18723	6.10e-04	7.67e-03	20
GO:19030527	Breast	Precancer	positive regulation of proteolysis involved in cellular protein catabolic process	17/1080	133/18723	1.68e-03	1.70e-02	17
GO:00457329	Breast	Precancer	positive regulation of protein catabolic process	25/1080	231/18723	1.87e-03	1.82e-02	25
GO:19018007	Breast	Precancer	positive regulation of proteasomal protein catabolic process	15/1080	114/18723	2.31e-03	2.15e-02	15
GO:00015036	Breast	Precancer	ossification	36/1080	408/18723	7.53e-03	4.98e-02	36
GO:004586214	Breast	IDC	positive regulation of proteolysis	66/1434	372/18723	9.76e-11	1.29e-08	66
GO:001049814	Breast	IDC	proteasomal protein catabolic process	75/1434	490/18723	5.59e-09	4.41e-07	75
GO:004217614	Breast	IDC	regulation of protein catabolic process	63/1434	391/18723	1.32e-08	9.61e-07	63
GO:190336214	Breast	IDC	regulation of cellular protein catabolic process	46/1434	255/18723	4.00e-08	2.68e-06	46
GO:190305014	Breast	IDC	regulation of proteolysis involved in cellular protein catabolic process	41/1434	221/18723	9.77e-08	5.84e-06	41

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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

SMC2

SNV

Missense_Mutation

novel

c.361N>G

p.Asn121Asp

p.N121D

O95347

protein_coding

deleterious(0.01)

benign(0.155)

TCGA-EY-A1GK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SMC2

SNV

Missense_Mutation

novel

c.67N>C

p.Phe23Leu

p.F23L

O95347

protein_coding

deleterious(0)

probably_damaging(0.962)

TCGA-QF-A5YS-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

SMC2

deletion

Frame_Shift_Del

c.814delN

p.Ile274Ter

p.I274*

O95347

protein_coding

TCGA-AJ-A3BG-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

SMC2

insertion

Frame_Shift_Ins

novel

c.813_814insA

p.Ile274AsnfsTer5

p.I274Nfs*5

O95347

protein_coding

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SMC2

deletion

Frame_Shift_Del

c.563delA

p.Lys188ArgfsTer5

p.K188Rfs*5

O95347

protein_coding

TCGA-B5-A0K6-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SMC2

insertion

Frame_Shift_Ins

novel

c.1914dupA

p.Val639SerfsTer4

p.V639Sfs*4

O95347

protein_coding

TCGA-BG-A0VW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SMC2

deletion

Frame_Shift_Del

c.563delA

p.Lys188ArgfsTer5

p.K188Rfs*5

O95347

protein_coding

TCGA-BG-A222-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SMC2

deletion

Frame_Shift_Del

c.2251delA

p.Thr751ProfsTer9

p.T751Pfs*9

O95347

protein_coding

TCGA-D1-A0ZO-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SMC2

deletion

Frame_Shift_Del

c.2251delA

p.Thr751ProfsTer9

p.T751Pfs*9

O95347

protein_coding

TCGA-D1-A160-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SMC2

deletion

Frame_Shift_Del

c.814delN

p.Ile274Ter

p.I274*

O95347

protein_coding

TCGA-D1-A167-01

Endometrium

uterine corpus endometrioid carcinoma

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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