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:190180022	Breast	DCIS	positive regulation of proteasomal protein catabolic process	22/1390	114/18723	2.92e-05	6.50e-04	22
GO:000989624	Breast	DCIS	positive regulation of catabolic process	61/1390	492/18723	5.32e-05	1.09e-03	61
GO:003133124	Breast	DCIS	positive regulation of cellular catabolic process	54/1390	427/18723	8.34e-05	1.58e-03	54
GO:000164921	Breast	DCIS	osteoblast differentiation	32/1390	229/18723	4.00e-04	5.48e-03	32
GO:000150321	Breast	DCIS	ossification	45/1390	408/18723	4.98e-03	3.72e-02	45
GO:00421762	Colorectum	MSS	regulation of protein catabolic process	145/3467	391/18723	2.03e-18	1.17e-15	145
GO:00098962	Colorectum	MSS	positive regulation of catabolic process	163/3467	492/18723	3.10e-15	9.22e-13	163
GO:19033622	Colorectum	MSS	regulation of cellular protein catabolic process	99/3467	255/18723	1.90e-14	5.37e-12	99
GO:00104982	Colorectum	MSS	proteasomal protein catabolic process	157/3467	490/18723	2.39e-13	5.25e-11	157
GO:00313312	Colorectum	MSS	positive regulation of cellular catabolic process	140/3467	427/18723	7.02e-13	1.33e-10	140
GO:00457322	Colorectum	MSS	positive regulation of protein catabolic process	85/3467	231/18723	3.66e-11	4.57e-09	85
GO:19030502	Colorectum	MSS	regulation of proteolysis involved in cellular protein catabolic process	82/3467	221/18723	4.97e-11	5.64e-09	82
GO:00458622	Colorectum	MSS	positive regulation of proteolysis	119/3467	372/18723	2.14e-10	2.09e-08	119
GO:00431612	Colorectum	MSS	proteasome-mediated ubiquitin-dependent protein catabolic process	127/3467	412/18723	7.70e-10	6.32e-08	127
GO:00611362	Colorectum	MSS	regulation of proteasomal protein catabolic process	67/3467	187/18723	1.45e-08	8.47e-07	67
GO:19033642	Colorectum	MSS	positive regulation of cellular protein catabolic process	57/3467	155/18723	6.01e-08	3.15e-06	57
GO:19030522	Colorectum	MSS	positive regulation of proteolysis involved in cellular protein catabolic process	48/3467	133/18723	1.21e-06	4.06e-05	48
GO:19018002	Colorectum	MSS	positive regulation of proteasomal protein catabolic process	40/3467	114/18723	1.96e-05	4.19e-04	40
GO:00016492	Colorectum	MSS	osteoblast differentiation	64/3467	229/18723	2.91e-04	3.83e-03	64
GO:00015032	Colorectum	MSS	ossification	96/3467	408/18723	6.09e-03	4.07e-02	96

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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.1472N>C

p.Arg491Thr

p.R491T

O95347

protein_coding

tolerated(0.56)

benign(0.01)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

SMC2

SNV

Missense_Mutation

rs776131090

c.2308N>A

p.Glu770Lys

p.E770K

O95347

protein_coding

tolerated(0.36)

benign(0.101)

TCGA-A8-A075-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

epirubicin

SMC2

SNV

Missense_Mutation

c.2269N>C

p.Glu757Gln

p.E757Q

O95347

protein_coding

tolerated(0.29)

benign(0.088)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SMC2

SNV

Missense_Mutation

novel

c.2271N>T

p.Glu757Asp

p.E757D

O95347

protein_coding

tolerated(0.07)

benign(0.049)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SMC2

SNV

Missense_Mutation

novel

c.3260G>A

p.Gly1087Asp

p.G1087D

O95347

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SMC2

SNV

Missense_Mutation

novel

c.2713N>A

p.Asp905Asn

p.D905N

O95347

protein_coding

deleterious(0.02)

benign(0.012)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SMC2

SNV

Missense_Mutation

novel

c.2899N>G

p.Gln967Glu

p.Q967E

O95347

protein_coding

tolerated(0.08)

benign(0.007)

TCGA-PE-A5DD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

SMC2

SNV

Missense_Mutation

c.1367N>A

p.Arg456Lys

p.R456K

O95347

protein_coding

tolerated(1)

benign(0)

TCGA-C5-A1MK-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

carboplatin

SMC2

SNV

Missense_Mutation

c.1831N>A

p.Glu611Lys

p.E611K

O95347

protein_coding

tolerated(0.43)

benign(0.061)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

SMC2

SNV

Missense_Mutation

c.2521G>A

p.Glu841Lys

p.E841K

O95347

protein_coding

tolerated(0.84)

benign(0.005)

TCGA-MA-AA3Y-01

Cervix

cervical & endocervical cancer

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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