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: KRT16

Gene summary for KRT16

Gene summary.

Gene information	Species	Human
	Gene symbol	KRT16
	Gene ID	3868
	Gene name	keratin 16
	Gene Alias	CK16
	Cytomap	17q21.2
	Gene Type	protein-coding
	GO ID	GO:0001667
	UniProtAcc	P08779

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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
3868	KRT16	GSM4909285	Human	Breast	IDC	3.85e-11	5.40e-01	0.21
3868	KRT16	GSM4909286	Human	Breast	IDC	3.23e-06	-2.45e-01	0.1081
3868	KRT16	GSM4909290	Human	Breast	IDC	1.82e-05	-2.68e-01	0.2096
3868	KRT16	GSM4909291	Human	Breast	IDC	1.32e-04	-2.73e-01	0.1753
3868	KRT16	GSM4909293	Human	Breast	IDC	1.22e-03	-2.50e-01	0.1581
3868	KRT16	GSM4909294	Human	Breast	IDC	1.39e-04	-2.59e-01	0.2022
3868	KRT16	GSM4909295	Human	Breast	IDC	6.48e-13	8.82e-01	0.0898
3868	KRT16	GSM4909296	Human	Breast	IDC	1.05e-06	-2.63e-01	0.1524
3868	KRT16	GSM4909297	Human	Breast	IDC	1.01e-03	-2.19e-01	0.1517
3868	KRT16	GSM4909298	Human	Breast	IDC	2.27e-06	-2.72e-01	0.1551
3868	KRT16	GSM4909301	Human	Breast	IDC	1.75e-09	-2.81e-01	0.1577
3868	KRT16	GSM4909302	Human	Breast	IDC	4.60e-07	-2.38e-01	0.1545
3868	KRT16	GSM4909303	Human	Breast	IDC	2.16e-02	-2.81e-01	0.0438
3868	KRT16	GSM4909304	Human	Breast	IDC	5.67e-08	-2.79e-01	0.1636
3868	KRT16	GSM4909307	Human	Breast	IDC	1.00e-03	-2.23e-01	0.1569
3868	KRT16	GSM4909308	Human	Breast	IDC	5.96e-11	-2.81e-01	0.158
3868	KRT16	GSM4909311	Human	Breast	IDC	1.65e-06	-2.39e-01	0.1534
3868	KRT16	GSM4909312	Human	Breast	IDC	1.60e-11	-2.81e-01	0.1552
3868	KRT16	GSM4909319	Human	Breast	IDC	8.04e-10	-2.77e-01	0.1563
3868	KRT16	GSM4909320	Human	Breast	IDC	3.28e-03	-2.81e-01	0.1575

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
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

∗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:00075688	Breast	Precancer	aging	41/1080	339/18723	5.95e-06	1.71e-04	41
GO:00106319	Breast	Precancer	epithelial cell migration	40/1080	357/18723	4.57e-05	9.71e-04	40
GO:00901329	Breast	Precancer	epithelium migration	40/1080	360/18723	5.51e-05	1.14e-03	40
GO:00901309	Breast	Precancer	tissue migration	40/1080	365/18723	7.48e-05	1.47e-03	40
GO:0045104	Breast	Precancer	intermediate filament cytoskeleton organization	11/1080	51/18723	1.26e-04	2.22e-03	11
GO:0045103	Breast	Precancer	intermediate filament-based process	11/1080	52/18723	1.52e-04	2.60e-03	11
GO:00508789	Breast	Precancer	regulation of body fluid levels	40/1080	379/18723	1.68e-04	2.77e-03	40
GO:00016678	Breast	Precancer	ameboidal-type cell migration	47/1080	475/18723	2.19e-04	3.35e-03	47
GO:00085445	Breast	Precancer	epidermis development	35/1080	324/18723	2.71e-04	3.96e-03	35
GO:00099136	Breast	Precancer	epidermal cell differentiation	23/1080	202/18723	1.43e-03	1.50e-02	23
GO:00302163	Breast	Precancer	keratinocyte differentiation	17/1080	139/18723	2.71e-03	2.39e-02	17
GO:000756813	Breast	IDC	aging	52/1434	339/18723	1.14e-06	5.10e-05	52
GO:000166714	Breast	IDC	ameboidal-type cell migration	64/1434	475/18723	6.65e-06	2.05e-04	64
GO:001063112	Breast	IDC	epithelial cell migration	51/1434	357/18723	1.14e-05	3.08e-04	51
GO:009013212	Breast	IDC	epithelium migration	51/1434	360/18723	1.44e-05	3.70e-04	51
GO:009013012	Breast	IDC	tissue migration	51/1434	365/18723	2.11e-05	5.11e-04	51
GO:005087813	Breast	IDC	regulation of body fluid levels	50/1434	379/18723	1.12e-04	2.10e-03	50
GO:00512712	Breast	IDC	negative regulation of cellular component movement	48/1434	367/18723	1.88e-04	3.12e-03	48
GO:20001462	Breast	IDC	negative regulation of cell motility	46/1434	359/18723	4.01e-04	5.60e-03	46
GO:00303362	Breast	IDC	negative regulation of cell migration	43/1434	344/18723	1.01e-03	1.13e-02	43

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0491518	Breast	Precancer	Estrogen signaling pathway	28/684	138/8465	4.10e-06	5.39e-05	4.13e-05	28
hsa0491519	Breast	Precancer	Estrogen signaling pathway	28/684	138/8465	4.10e-06	5.39e-05	4.13e-05	28
hsa0491523	Breast	IDC	Estrogen signaling pathway	35/867	138/8465	2.55e-07	5.18e-06	3.88e-06	35
hsa0491533	Breast	IDC	Estrogen signaling pathway	35/867	138/8465	2.55e-07	5.18e-06	3.88e-06	35
hsa0491542	Breast	DCIS	Estrogen signaling pathway	35/846	138/8465	1.40e-07	2.51e-06	1.85e-06	35
hsa05150	Breast	DCIS	Staphylococcus aureus infection	19/846	96/8465	2.68e-03	1.67e-02	1.23e-02	19
hsa0491552	Breast	DCIS	Estrogen signaling pathway	35/846	138/8465	1.40e-07	2.51e-06	1.85e-06	35
hsa051501	Breast	DCIS	Staphylococcus aureus infection	19/846	96/8465	2.68e-03	1.67e-02	1.23e-02	19
hsa0491520	Cervix	CC	Estrogen signaling pathway	44/1267	138/8465	3.55e-07	3.97e-06	2.35e-06	44
hsa04915110	Cervix	CC	Estrogen signaling pathway	44/1267	138/8465	3.55e-07	3.97e-06	2.35e-06	44
hsa051504	Cervix	HSIL_HPV	Staphylococcus aureus infection	21/459	96/8465	2.93e-08	1.43e-06	1.16e-06	21
hsa0491524	Cervix	HSIL_HPV	Estrogen signaling pathway	19/459	138/8465	1.54e-04	1.74e-03	1.40e-03	19
hsa0515011	Cervix	HSIL_HPV	Staphylococcus aureus infection	21/459	96/8465	2.93e-08	1.43e-06	1.16e-06	21
hsa0491534	Cervix	HSIL_HPV	Estrogen signaling pathway	19/459	138/8465	1.54e-04	1.74e-03	1.40e-03	19
hsa0491529	Oral cavity	EOLP	Estrogen signaling pathway	38/1218	138/8465	3.78e-05	1.82e-04	1.07e-04	38
hsa04915113	Oral cavity	EOLP	Estrogen signaling pathway	38/1218	138/8465	3.78e-05	1.82e-04	1.07e-04	38
hsa04915210	Oral cavity	NEOLP	Estrogen signaling pathway	29/1112	138/8465	6.33e-03	2.34e-02	1.47e-02	29
hsa0491537	Oral cavity	NEOLP	Estrogen signaling pathway	29/1112	138/8465	6.33e-03	2.34e-02	1.47e-02	29
hsa0491527	Prostate	BPH	Estrogen signaling pathway	48/1718	138/8465	4.60e-05	3.16e-04	1.96e-04	48
hsa04915112	Prostate	BPH	Estrogen signaling pathway	48/1718	138/8465	4.60e-05	3.16e-04	1.96e-04	48

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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

KRT16

SNV

Missense_Mutation

rs765819730

c.956N>C

p.Val319Ala

p.V319A

P08779

protein_coding

deleterious(0.05)

possibly_damaging(0.631)

TCGA-LL-A9Q3-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Immunotherapy

herceptin

KRT16

insertion

Nonsense_Mutation

novel

c.1080_1081insATATATATATAAATAAAATACAC

p.Leu361IlefsTer4

p.L361Ifs*4

P08779

protein_coding

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

KRT16

insertion

Frame_Shift_Ins

novel

c.1078_1079insTATATACATTTAT

p.Ser360IlefsTer37

p.S360Ifs*37

P08779

protein_coding

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

KRT16

insertion

Nonsense_Mutation

novel

c.960_961insACGTGTGACGAGTGCAACTCAGTGCAATTCAGTATATGAAACATTCA

p.Ser321ThrfsTer13

p.S321Tfs*13

P08779

protein_coding

TCGA-B6-A1KF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KRT16

SNV

Missense_Mutation

c.304T>G

p.Phe102Val

p.F102V

P08779

protein_coding

tolerated(0.26)

benign(0.011)

TCGA-C5-A7CO-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

KRT16

SNV

Missense_Mutation

novel

c.1124N>A

p.Ile375Asn

p.I375N

P08779

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-VS-A9UI-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

KRT16

SNV

Missense_Mutation

rs764661195

c.1358G>A

p.Arg453His

p.R453H

P08779

protein_coding

tolerated(0.1)

benign(0)

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

KRT16

SNV

Missense_Mutation

novel

c.22N>C

p.Phe8Leu

p.F8L

P08779

protein_coding

tolerated(0.07)

benign(0.066)

TCGA-AA-A00N-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

KRT16

SNV

Missense_Mutation

c.73N>T

p.Gly25Trp

p.G25W

P08779

protein_coding

deleterious(0)

benign(0)

TCGA-CM-5344-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

oxaliplatin

KRT16

SNV

Missense_Mutation

c.86N>A

p.Ser29Asn

p.S29N

P08779

protein_coding

deleterious(0.01)

benign(0.136)

TCGA-D5-6932-01

Colorectum

colon adenocarcinoma

Male

>=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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