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: SMG6

Gene summary for SMG6

Gene summary.

Gene information	Species	Human
	Gene symbol	SMG6
	Gene ID	23293
	Gene name	SMG6 nonsense mediated mRNA decay factor
	Gene Alias	C17orf31
	Cytomap	17p13.3
	Gene Type	protein-coding
	GO ID	GO:0000184
	UniProtAcc	Q86US8

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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
23293	SMG6	CCI_1	Human	Cervix	CC	2.31e-07	7.50e-01	0.528
23293	SMG6	CCI_2	Human	Cervix	CC	2.29e-07	7.42e-01	0.5249
23293	SMG6	CCI_3	Human	Cervix	CC	1.82e-05	4.68e-01	0.516
23293	SMG6	HTA11_3410_2000001011	Human	Colorectum	AD	1.96e-06	-4.20e-01	0.0155
23293	SMG6	HTA11_347_2000001011	Human	Colorectum	AD	1.53e-04	4.06e-01	-0.1954
23293	SMG6	HTA11_99999970781_79442	Human	Colorectum	MSS	5.74e-11	-4.34e-01	0.294
23293	SMG6	HTA11_99999971662_82457	Human	Colorectum	MSS	8.84e-06	-4.09e-01	0.3859
23293	SMG6	HTA11_99999974143_84620	Human	Colorectum	MSS	3.02e-04	-3.35e-01	0.3005
23293	SMG6	A001-C-207	Human	Colorectum	FAP	3.34e-02	-2.18e-01	0.1278
23293	SMG6	A015-C-203	Human	Colorectum	FAP	2.14e-25	-4.12e-01	-0.1294
23293	SMG6	A015-C-204	Human	Colorectum	FAP	2.82e-06	-4.37e-01	-0.0228
23293	SMG6	A014-C-040	Human	Colorectum	FAP	4.10e-03	-3.36e-01	-0.1184
23293	SMG6	A002-C-201	Human	Colorectum	FAP	4.81e-09	-3.45e-01	0.0324
23293	SMG6	A002-C-203	Human	Colorectum	FAP	1.47e-02	-1.22e-01	0.2786
23293	SMG6	A001-C-119	Human	Colorectum	FAP	1.89e-02	-1.57e-01	-0.1557
23293	SMG6	A001-C-108	Human	Colorectum	FAP	6.42e-13	-2.65e-01	-0.0272
23293	SMG6	A002-C-205	Human	Colorectum	FAP	4.97e-18	-3.30e-01	-0.1236
23293	SMG6	A001-C-104	Human	Colorectum	FAP	9.86e-03	-1.95e-01	0.0184
23293	SMG6	A015-C-006	Human	Colorectum	FAP	2.49e-12	-3.36e-01	-0.0994
23293	SMG6	A015-C-106	Human	Colorectum	FAP	1.27e-09	-2.64e-01	-0.0511

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:0015931	Colorectum	AD	nucleobase-containing compound transport	73/3918	222/18723	2.02e-05	4.10e-04	73
GO:2000278	Colorectum	AD	regulation of DNA biosynthetic process	41/3918	106/18723	2.17e-05	4.33e-04	41
GO:0050657	Colorectum	AD	nucleic acid transport	57/3918	163/18723	2.22e-05	4.39e-04	57
GO:0050658	Colorectum	AD	RNA transport	57/3918	163/18723	2.22e-05	4.39e-04	57
GO:0035303	Colorectum	AD	regulation of dephosphorylation	46/3918	128/18723	6.20e-05	1.04e-03	46
GO:0051972	Colorectum	AD	regulation of telomerase activity	22/3918	47/18723	6.45e-05	1.07e-03	22
GO:0051168	Colorectum	AD	nuclear export	53/3918	154/18723	6.89e-05	1.11e-03	53
GO:0032204	Colorectum	AD	regulation of telomere maintenance	31/3918	80/18723	2.01e-04	2.67e-03	31
GO:0000956	Colorectum	AD	nuclear-transcribed mRNA catabolic process	40/3918	112/18723	2.11e-04	2.79e-03	40
GO:0033044	Colorectum	AD	regulation of chromosome organization	60/3918	187/18723	2.25e-04	2.94e-03	60
GO:0000723	Colorectum	AD	telomere maintenance	43/3918	131/18723	9.77e-04	9.20e-03	43
GO:0010833	Colorectum	AD	telomere maintenance via telomere lengthening	29/3918	81/18723	1.42e-03	1.22e-02	29
GO:0071897	Colorectum	AD	DNA biosynthetic process	55/3918	180/18723	1.46e-03	1.24e-02	55
GO:0051028	Colorectum	AD	mRNA transport	42/3918	130/18723	1.57e-03	1.32e-02	42
GO:1904356	Colorectum	AD	regulation of telomere maintenance via telomere lengthening	23/3918	61/18723	1.96e-03	1.58e-02	23
GO:0007004	Colorectum	AD	telomere maintenance via telomerase	25/3918	69/18723	2.43e-03	1.88e-02	25
GO:0006278	Colorectum	AD	RNA-dependent DNA biosynthetic process	25/3918	75/18723	8.36e-03	4.89e-02	25
GO:00064012	Colorectum	MSS	RNA catabolic process	102/3467	278/18723	5.07e-13	1.02e-10	102
GO:00064022	Colorectum	MSS	mRNA catabolic process	89/3467	232/18723	8.70e-13	1.60e-10	89
GO:00442702	Colorectum	MSS	cellular nitrogen compound catabolic process	141/3467	451/18723	2.95e-11	3.83e-09	141

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa03015	Colorectum	AD	mRNA surveillance pathway	35/2092	97/8465	7.95e-03	3.13e-02	2.00e-02	35
hsa030151	Colorectum	AD	mRNA surveillance pathway	35/2092	97/8465	7.95e-03	3.13e-02	2.00e-02	35
hsa030152	Colorectum	FAP	mRNA surveillance pathway	26/1404	97/8465	7.11e-03	2.64e-02	1.60e-02	26
hsa030153	Colorectum	FAP	mRNA surveillance pathway	26/1404	97/8465	7.11e-03	2.64e-02	1.60e-02	26
hsa0301524	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa0301534	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa030158	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa0301513	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa0301523	Oral cavity	LP	mRNA surveillance pathway	50/2418	97/8465	1.39e-06	1.50e-05	9.66e-06	50
hsa0301533	Oral cavity	LP	mRNA surveillance pathway	50/2418	97/8465	1.39e-06	1.50e-05	9.66e-06	50
hsa0301541	Oral cavity	EOLP	mRNA surveillance pathway	30/1218	97/8465	2.26e-05	1.20e-04	7.07e-05	30
hsa0301551	Oral cavity	EOLP	mRNA surveillance pathway	30/1218	97/8465	2.26e-05	1.20e-04	7.07e-05	30
hsa030156	Oral cavity	NEOLP	mRNA surveillance pathway	25/1112	97/8465	5.70e-04	3.18e-03	2.00e-03	25
hsa030157	Oral cavity	NEOLP	mRNA surveillance pathway	25/1112	97/8465	5.70e-04	3.18e-03	2.00e-03	25

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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

SMG6

SNV

Missense_Mutation

c.1631N>G

p.Tyr544Cys

p.Y544C

Q86US8

protein_coding

tolerated(0.09)

possibly_damaging(0.894)

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SMG6

SNV

Missense_Mutation

c.3957N>C

p.Glu1319Asp

p.E1319D

Q86US8

protein_coding

tolerated(0.07)

probably_damaging(0.985)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SMG6

SNV

Missense_Mutation

novel

c.812N>T

p.Ala271Val

p.A271V

Q86US8

protein_coding

tolerated_low_confidence(1)

benign(0.014)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SMG6

SNV

Missense_Mutation

c.93N>A

p.Asn31Lys

p.N31K

Q86US8

protein_coding

tolerated_low_confidence(0.05)

benign(0.115)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

SMG6

SNV

Missense_Mutation

novel

c.3606N>G

p.Ile1202Met

p.I1202M

Q86US8

protein_coding

deleterious(0)

probably_damaging(0.942)

TCGA-OL-A5RW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SMG6

SNV

Missense_Mutation

novel

c.1133C>T

p.Pro378Leu

p.P378L

Q86US8

protein_coding

tolerated_low_confidence(0.25)

benign(0)

TCGA-OL-A5RZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SMG6

SNV

Missense_Mutation

novel

c.1132C>A

p.Pro378Thr

p.P378T

Q86US8

protein_coding

tolerated_low_confidence(0.24)

benign(0)

TCGA-OL-A5RZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SMG6

SNV

Missense_Mutation

novel

c.995C>T

p.Ser332Phe

p.S332F

Q86US8

protein_coding

deleterious_low_confidence(0.02)

benign(0.135)

TCGA-OL-A5RZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SMG6

insertion

Nonsense_Mutation

novel

c.1062_1063insTTATAGTAA

p.Phe354_Asp355insLeuTerTer

p.F354_D355insL**

Q86US8

protein_coding

TCGA-A8-A096-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SMG6

insertion

Frame_Shift_Ins

novel

c.1061_1062insGAAA

p.Phe354LeufsTer20

p.F354Lfs*20

Q86US8

protein_coding

TCGA-A8-A096-01

Breast

breast invasive 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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