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: KRT2

Gene summary for KRT2

Gene summary.

Gene information	Species	Human
	Gene symbol	KRT2
	Gene ID	3849
	Gene name	keratin 2
	Gene Alias	CK-2e
	Cytomap	12q13.13
	Gene Type	protein-coding
	GO ID	GO:0001667
	UniProtAcc	P35908

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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
3849	KRT2	P4_S8_cSCC	Human	Skin	cSCC	1.75e-20	3.71e-01	-0.3095
3849	KRT2	cSCC_p11	Human	Skin	cSCC	8.41e-11	2.91e-01	-0.2102
3849	KRT2	cSCC_p3	Human	Skin	cSCC	5.59e-19	6.90e-01	-0.2085
3849	KRT2	cSCC_p7	Human	Skin	cSCC	1.05e-04	3.65e-01	-0.2332

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:0031667	Colorectum	AD	response to nutrient levels	138/3918	474/18723	1.22e-05	2.68e-04	138
GO:0050708	Colorectum	AD	regulation of protein secretion	83/3918	268/18723	6.59e-05	1.07e-03	83
GO:0009306	Colorectum	AD	protein secretion	105/3918	359/18723	1.05e-04	1.57e-03	105
GO:0035592	Colorectum	AD	establishment of protein localization to extracellular region	105/3918	360/18723	1.18e-04	1.73e-03	105
GO:0042594	Colorectum	AD	response to starvation	63/3918	197/18723	1.77e-04	2.38e-03	63
GO:0071692	Colorectum	AD	protein localization to extracellular region	106/3918	368/18723	1.86e-04	2.49e-03	106
GO:0071496	Colorectum	AD	cellular response to external stimulus	94/3918	320/18723	1.98e-04	2.64e-03	94
GO:0009267	Colorectum	AD	cellular response to starvation	51/3918	156/18723	3.90e-04	4.44e-03	51
GO:0031668	Colorectum	AD	cellular response to extracellular stimulus	71/3918	246/18723	1.86e-03	1.52e-02	71
GO:0031669	Colorectum	AD	cellular response to nutrient levels	63/3918	215/18723	2.19e-03	1.73e-02	63
GO:00316671	Colorectum	SER	response to nutrient levels	106/2897	474/18723	3.94e-05	1.00e-03	106
GO:00507081	Colorectum	SER	regulation of protein secretion	63/2897	268/18723	3.42e-04	5.39e-03	63
GO:00093061	Colorectum	SER	protein secretion	79/2897	359/18723	5.99e-04	8.19e-03	79
GO:00355921	Colorectum	SER	establishment of protein localization to extracellular region	79/2897	360/18723	6.54e-04	8.77e-03	79
GO:00716921	Colorectum	SER	protein localization to extracellular region	80/2897	368/18723	8.13e-04	1.01e-02	80
GO:00425941	Colorectum	SER	response to starvation	47/2897	197/18723	1.31e-03	1.45e-02	47
GO:00714961	Colorectum	SER	cellular response to external stimulus	70/2897	320/18723	1.40e-03	1.53e-02	70
GO:00092671	Colorectum	SER	cellular response to starvation	38/2897	156/18723	2.45e-03	2.32e-02	38
GO:00316681	Colorectum	SER	cellular response to extracellular stimulus	54/2897	246/18723	4.26e-03	3.45e-02	54
GO:00316691	Colorectum	SER	cellular response to nutrient levels	48/2897	215/18723	4.82e-03	3.78e-02	48

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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

KRT2

SNV

Missense_Mutation

rs371361222

c.700N>A

p.Asp234Asn

p.D234N

P35908

protein_coding

tolerated(0.5)

benign(0.058)

TCGA-A2-A04T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

KRT2

SNV

Missense_Mutation

novel

c.347N>C

p.Gly116Ala

p.G116A

P35908

protein_coding

tolerated(0.49)

benign(0.232)

TCGA-A8-A09A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

KRT2

SNV

Missense_Mutation

rs137852629

c.1459G>A

p.Glu487Lys

p.E487K

P35908

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KRT2

SNV

Missense_Mutation

rs776596709

c.986N>T

p.Thr329Ile

p.T329I

P35908

protein_coding

deleterious(0)

benign(0.348)

TCGA-AO-A124-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

KRT2

SNV

Missense_Mutation

rs182397714

c.851N>T

p.Thr284Met

p.T284M

P35908

protein_coding

tolerated(0.13)

probably_damaging(0.971)

TCGA-C8-A12W-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

KRT2

SNV

Missense_Mutation

c.1171N>C

p.Glu391Gln

p.E391Q

P35908

protein_coding

deleterious(0.04)

benign(0.417)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

KRT2

SNV

Missense_Mutation

c.1020N>A

p.Ser340Arg

p.S340R

P35908

protein_coding

deleterious(0)

possibly_damaging(0.9)

TCGA-JL-A3YW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

KRT2

SNV

Missense_Mutation

novel

c.922N>G

p.Gln308Glu

p.Q308E

P35908

protein_coding

tolerated(0.17)

benign(0.173)

TCGA-LL-A8F5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

KRT2

deletion

Frame_Shift_Del

novel

c.146delN

p.Gly49ValfsTer87

p.G49Vfs*87

P35908

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

KRT2

SNV

Missense_Mutation

novel

c.1558N>T

p.Gly520Cys

p.G520C

P35908

protein_coding

deleterious(0.02)

possibly_damaging(0.52)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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