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: ANO6

Gene summary for ANO6

Gene summary.

Gene information	Species	Human
	Gene symbol	ANO6
	Gene ID	196527
	Gene name	anoctamin 6
	Gene Alias	BDPLT7
	Cytomap	12q12
	Gene Type	protein-coding
	GO ID	GO:0001503
	UniProtAcc	B3KX12

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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
196527	ANO6	CCI_1	Human	Cervix	CC	7.31e-06	7.12e-01	0.528
196527	ANO6	CCI_3	Human	Cervix	CC	1.52e-06	6.17e-01	0.516
196527	ANO6	LZE4T	Human	Esophagus	ESCC	5.30e-07	3.22e-01	0.0811
196527	ANO6	LZE7T	Human	Esophagus	ESCC	7.88e-03	4.37e-01	0.0667
196527	ANO6	LZE8T	Human	Esophagus	ESCC	5.98e-04	9.43e-02	0.067
196527	ANO6	LZE20T	Human	Esophagus	ESCC	7.53e-09	4.67e-01	0.0662
196527	ANO6	LZE22T	Human	Esophagus	ESCC	2.49e-03	1.67e-01	0.068
196527	ANO6	LZE24T	Human	Esophagus	ESCC	1.17e-04	2.46e-01	0.0596
196527	ANO6	LZE21T	Human	Esophagus	ESCC	1.11e-02	1.70e-01	0.0655
196527	ANO6	P1T-E	Human	Esophagus	ESCC	2.09e-06	3.14e-01	0.0875
196527	ANO6	P2T-E	Human	Esophagus	ESCC	4.80e-30	5.73e-01	0.1177
196527	ANO6	P4T-E	Human	Esophagus	ESCC	4.55e-49	1.13e+00	0.1323
196527	ANO6	P5T-E	Human	Esophagus	ESCC	1.19e-22	5.12e-01	0.1327
196527	ANO6	P8T-E	Human	Esophagus	ESCC	7.03e-19	4.65e-01	0.0889
196527	ANO6	P9T-E	Human	Esophagus	ESCC	1.49e-07	2.54e-01	0.1131
196527	ANO6	P10T-E	Human	Esophagus	ESCC	4.91e-17	2.62e-01	0.116
196527	ANO6	P11T-E	Human	Esophagus	ESCC	9.84e-17	6.43e-01	0.1426
196527	ANO6	P12T-E	Human	Esophagus	ESCC	2.52e-18	3.09e-01	0.1122
196527	ANO6	P15T-E	Human	Esophagus	ESCC	3.05e-10	3.26e-01	0.1149
196527	ANO6	P16T-E	Human	Esophagus	ESCC	1.14e-08	1.42e-01	0.1153

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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
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
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:0002526	Liver	NAFLD	acute inflammatory response	26/1882	112/18723	3.68e-05	9.23e-04	26
GO:0050820	Liver	NAFLD	positive regulation of coagulation	10/1882	24/18723	5.36e-05	1.22e-03	10
GO:00444037	Liver	NAFLD	biological process involved in symbiotic interaction	50/1882	290/18723	1.03e-04	2.04e-03	50
GO:00508787	Liver	NAFLD	regulation of body fluid levels	60/1882	379/18723	2.61e-04	4.23e-03	60
GO:1904019	Liver	NAFLD	epithelial cell apoptotic process	24/1882	121/18723	8.75e-04	1.07e-02	24
GO:00301005	Liver	NAFLD	regulation of endocytosis	35/1882	211/18723	2.09e-03	2.06e-02	35
GO:0050764	Liver	NAFLD	regulation of phagocytosis	19/1882	95/18723	2.61e-03	2.41e-02	19
GO:00347643	Liver	NAFLD	positive regulation of transmembrane transport	35/1882	219/18723	3.92e-03	3.32e-02	35
GO:00325356	Liver	NAFLD	regulation of cellular component size	55/1882	383/18723	4.31e-03	3.55e-02	55
GO:0050766	Liver	NAFLD	positive regulation of phagocytosis	14/1882	66/18723	5.28e-03	4.08e-02	14
GO:0051817	Liver	NAFLD	modulation of process of other organism involved in symbiotic interaction	16/1882	81/18723	6.20e-03	4.62e-02	16
GO:00517017	Liver	NAFLD	biological process involved in interaction with host	32/1882	203/18723	6.90e-03	4.87e-02	32
GO:001603212	Liver	Cirrhotic	viral process	203/4634	415/18723	5.40e-27	3.76e-24	203
GO:004440312	Liver	Cirrhotic	biological process involved in symbiotic interaction	131/4634	290/18723	2.00e-14	1.84e-12	131
GO:005170112	Liver	Cirrhotic	biological process involved in interaction with host	88/4634	203/18723	4.55e-09	1.82e-07	88
GO:00518171	Liver	Cirrhotic	modulation of process of other organism involved in symbiotic interaction	44/4634	81/18723	1.11e-08	4.26e-07	44
GO:004206012	Liver	Cirrhotic	wound healing	155/4634	422/18723	2.12e-08	7.56e-07	155
GO:190303611	Liver	Cirrhotic	positive regulation of response to wounding	38/4634	72/18723	2.98e-07	7.18e-06	38
GO:009030311	Liver	Cirrhotic	positive regulation of wound healing	33/4634	59/18723	3.00e-07	7.21e-06	33
GO:00358213	Liver	Cirrhotic	modulation of process of other organism	49/4634	106/18723	1.20e-06	2.43e-05	49

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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

ANO6

SNV

Missense_Mutation

c.1075N>T

p.His359Tyr

p.H359Y

Q4KMQ2

protein_coding

tolerated(0.07)

benign(0.067)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ANO6

SNV

Missense_Mutation

c.595G>C

p.Glu199Gln

p.E199Q

Q4KMQ2

protein_coding

deleterious(0.02)

benign(0.433)

TCGA-C8-A275-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ANO6

SNV

Missense_Mutation

rs745465915

c.361G>A

p.Glu121Lys

p.E121K

Q4KMQ2

protein_coding

deleterious(0)

benign(0.393)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

ANO6

SNV

Missense_Mutation

rs781608617

c.1259N>A

p.Arg420His

p.R420H

Q4KMQ2

protein_coding

deleterious(0)

possibly_damaging(0.871)

TCGA-D8-A1JF-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

ANO6

SNV

Missense_Mutation

c.1976N>C

p.Arg659Thr

p.R659T

Q4KMQ2

protein_coding

tolerated(0.62)

benign(0)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ANO6

SNV

Missense_Mutation

novel

c.1953N>A

p.Met651Ile

p.M651I

Q4KMQ2

protein_coding

tolerated(0.39)

benign(0.044)

TCGA-EW-A1OV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

epirubicin

ANO6

SNV

Missense_Mutation

novel

c.1273N>C

p.Glu425Gln

p.E425Q

Q4KMQ2

protein_coding

tolerated(0.08)

possibly_damaging(0.593)

TCGA-EW-A3E8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

anastrozole

ANO6

SNV

Missense_Mutation

novel

c.2048N>C

p.Gly683Ala

p.G683A

Q4KMQ2

protein_coding

tolerated(0.07)

possibly_damaging(0.678)

TCGA-LL-A441-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

ANO6

insertion

Frame_Shift_Ins

novel

c.2465_2466insGACCAGCC

p.Asn823ThrfsTer32

p.N823Tfs*32

Q4KMQ2

protein_coding

TCGA-B6-A0IN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ANO6

insertion

Frame_Shift_Ins

novel

c.2466_2467insGGCCAACATGACAA

p.Asn823GlyfsTer34

p.N823Gfs*34

Q4KMQ2

protein_coding

TCGA-B6-A0IN-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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