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: BIRC6

Gene summary for BIRC6

Gene summary.

Gene information	Species	Human
	Gene symbol	BIRC6
	Gene ID	57448
	Gene name	baculoviral IAP repeat containing 6
	Gene Alias	APOLLON
	Cytomap	2p22.3
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q9NR09

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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
57448	BIRC6	CA_HPV_1	Human	Cervix	CC	1.15e-02	1.86e-02	0.0264
57448	BIRC6	CCI_1	Human	Cervix	CC	3.57e-05	1.44e+00	0.528
57448	BIRC6	CCI_2	Human	Cervix	CC	1.43e-15	1.78e+00	0.5249
57448	BIRC6	CCI_3	Human	Cervix	CC	9.75e-19	1.19e+00	0.516
57448	BIRC6	HTA11_3410_2000001011	Human	Colorectum	AD	5.00e-30	-6.20e-01	0.0155
57448	BIRC6	HTA11_2951_2000001011	Human	Colorectum	AD	1.28e-03	-7.65e-01	0.0216
57448	BIRC6	HTA11_347_2000001011	Human	Colorectum	AD	2.15e-16	6.69e-01	-0.1954
57448	BIRC6	HTA11_411_2000001011	Human	Colorectum	SER	7.50e-09	7.07e-01	-0.2602
57448	BIRC6	HTA11_3361_2000001011	Human	Colorectum	AD	1.77e-06	-4.63e-01	-0.1207
57448	BIRC6	HTA11_866_3004761011	Human	Colorectum	AD	1.96e-12	-5.71e-01	0.096
57448	BIRC6	HTA11_9408_2000001011	Human	Colorectum	AD	6.26e-07	-8.83e-01	0.0451
57448	BIRC6	HTA11_10711_2000001011	Human	Colorectum	AD	1.43e-02	-4.46e-01	0.0338
57448	BIRC6	HTA11_7696_3000711011	Human	Colorectum	AD	9.72e-05	-3.57e-01	0.0674
57448	BIRC6	HTA11_99999965062_69753	Human	Colorectum	MSI-H	2.56e-04	7.71e-01	0.3487
57448	BIRC6	HTA11_99999965104_69814	Human	Colorectum	MSS	3.18e-11	6.90e-01	0.281
57448	BIRC6	HTA11_99999974143_84620	Human	Colorectum	MSS	1.48e-07	-3.69e-01	0.3005
57448	BIRC6	F007	Human	Colorectum	FAP	3.69e-03	-2.15e-01	0.1176
57448	BIRC6	A001-C-207	Human	Colorectum	FAP	5.36e-03	-1.19e-01	0.1278
57448	BIRC6	A015-C-203	Human	Colorectum	FAP	1.70e-36	-4.81e-01	-0.1294
57448	BIRC6	A015-C-204	Human	Colorectum	FAP	3.20e-07	-3.37e-01	-0.0228

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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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
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
Prostate		BPH: Benign Prostatic Hyperplasia
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:200123310	Cervix	CC	regulation of apoptotic signaling pathway	96/2311	356/18723	4.08e-14	3.05e-11	96
GO:005254710	Cervix	CC	regulation of peptidase activity	112/2311	461/18723	6.70e-13	3.08e-10	112
GO:005254810	Cervix	CC	regulation of endopeptidase activity	103/2311	432/18723	1.89e-11	5.14e-09	103
GO:004586110	Cervix	CC	negative regulation of proteolysis	80/2311	351/18723	2.88e-08	1.98e-06	80
GO:200123410	Cervix	CC	negative regulation of apoptotic signaling pathway	56/2311	224/18723	1.39e-07	6.70e-06	56
GO:00513469	Cervix	CC	negative regulation of hydrolase activity	81/2311	379/18723	4.27e-07	1.67e-05	81
GO:00018908	Cervix	CC	placenta development	40/2311	144/18723	4.59e-07	1.77e-05	40
GO:00104669	Cervix	CC	negative regulation of peptidase activity	60/2311	262/18723	1.27e-06	4.34e-05	60
GO:00614588	Cervix	CC	reproductive system development	87/2311	427/18723	1.37e-06	4.55e-05	87
GO:00486088	Cervix	CC	reproductive structure development	86/2311	424/18723	1.90e-06	5.97e-05	86
GO:009719110	Cervix	CC	extrinsic apoptotic signaling pathway	52/2311	219/18723	2.06e-06	6.34e-05	52
GO:001095110	Cervix	CC	negative regulation of endopeptidase activity	56/2311	252/18723	7.43e-06	1.74e-04	56
GO:200123610	Cervix	CC	regulation of extrinsic apoptotic signaling pathway	37/2311	151/18723	2.80e-05	4.65e-04	37
GO:00017018	Cervix	CC	in utero embryonic development	71/2311	367/18723	7.21e-05	1.00e-03	71
GO:00513021	Cervix	CC	regulation of cell division	39/2311	177/18723	2.05e-04	2.33e-03	39
GO:00018928	Cervix	CC	embryonic placenta development	22/2311	82/18723	2.89e-04	3.12e-03	22
GO:00009107	Cervix	CC	cytokinesis	37/2311	173/18723	5.40e-04	5.23e-03	37
GO:200123710	Cervix	CC	negative regulation of extrinsic apoptotic signaling pathway	23/2311	97/18723	1.39e-03	1.10e-02	23
GO:0032465	Cervix	CC	regulation of cytokinesis	22/2311	92/18723	1.55e-03	1.20e-02	22
GO:00607115	Cervix	CC	labyrinthine layer development	12/2311	44/18723	5.76e-03	3.30e-02	12

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0412014	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa0412015	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa04120	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa041201	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa041202	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041203	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041204	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa041205	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa0412016	Endometrium	AEH	Ubiquitin mediated proteolysis	41/1197	142/8465	3.42e-06	4.27e-05	3.13e-05	41
hsa0412017	Endometrium	AEH	Ubiquitin mediated proteolysis	41/1197	142/8465	3.42e-06	4.27e-05	3.13e-05	41
hsa0412023	Endometrium	EEC	Ubiquitin mediated proteolysis	41/1237	142/8465	7.86e-06	9.58e-05	7.14e-05	41
hsa0412033	Endometrium	EEC	Ubiquitin mediated proteolysis	41/1237	142/8465	7.86e-06	9.58e-05	7.14e-05	41
hsa0412026	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa04120111	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa0412027	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa042156	Esophagus	ESCC	Apoptosis - multiple species	25/4205	32/8465	9.13e-04	2.92e-03	1.49e-03	25
hsa0412036	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0421511	Esophagus	ESCC	Apoptosis - multiple species	25/4205	32/8465	9.13e-04	2.92e-03	1.49e-03	25
hsa0412010	Liver	NAFLD	Ubiquitin mediated proteolysis	44/1043	142/8465	2.59e-09	1.70e-07	1.37e-07	44
hsa0412011	Liver	NAFLD	Ubiquitin mediated proteolysis	44/1043	142/8465	2.59e-09	1.70e-07	1.37e-07	44

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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

BIRC6

SNV

Missense_Mutation

c.10511N>A

p.Ser3504Asn

p.S3504N

Q9NR09

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-A2-A0D0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

BIRC6

SNV

Missense_Mutation

c.11476N>G

p.Leu3826Val

p.L3826V

Q9NR09

protein_coding

tolerated(0.63)

benign(0.29)

TCGA-A2-A0YK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

BIRC6

SNV

Missense_Mutation

c.13787G>T

p.Ser4596Ile

p.S4596I

Q9NR09

protein_coding

deleterious(0)

possibly_damaging(0.863)

TCGA-A7-A13F-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

BIRC6

SNV

Missense_Mutation

c.13846C>A

p.Pro4616Thr

p.P4616T

Q9NR09

protein_coding

deleterious(0)

probably_damaging(0.954)

TCGA-A8-A097-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

BIRC6

SNV

Missense_Mutation

rs769761198

c.4802C>T

p.Thr1601Ile

p.T1601I

Q9NR09

protein_coding

tolerated(0.1)

possibly_damaging(0.791)

TCGA-A8-A0A6-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

epirubicin

BIRC6

SNV

Missense_Mutation

c.8318N>A

p.Gly2773Glu

p.G2773E

Q9NR09

protein_coding

deleterious(0.01)

probably_damaging(0.987)

TCGA-A8-A0A7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

BIRC6

SNV

Missense_Mutation

c.12614N>T

p.Ser4205Leu

p.S4205L

Q9NR09

protein_coding

tolerated(1)

benign(0.12)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BIRC6

SNV

Missense_Mutation

c.13264N>A

p.Glu4422Lys

p.E4422K

Q9NR09

protein_coding

tolerated(0.08)

probably_damaging(0.92)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BIRC6

SNV

Missense_Mutation

novel

c.9733N>T

p.Ala3245Ser

p.A3245S

Q9NR09

protein_coding

tolerated(0.52)

benign(0.007)

TCGA-AC-A3W6-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

BIRC6

SNV

Missense_Mutation

novel

c.6674N>T

p.Arg2225Ile

p.R2225I

Q9NR09

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AN-A046-01

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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