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: KRTCAP2

Gene summary for KRTCAP2

Gene summary.

Gene information	Species	Human
	Gene symbol	KRTCAP2
	Gene ID	200185
	Gene name	keratinocyte associated protein 2
	Gene Alias	KCP2
	Cytomap	1q22
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	Q8N6L1

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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
200185	KRTCAP2	GSM4909287	Human	Breast	IDC	7.98e-07	4.09e-01	0.2057
200185	KRTCAP2	GSM4909295	Human	Breast	IDC	9.93e-10	5.57e-01	0.0898
200185	KRTCAP2	GSM4909296	Human	Breast	IDC	6.18e-13	2.05e-01	0.1524
200185	KRTCAP2	GSM4909297	Human	Breast	IDC	7.61e-15	-2.08e-01	0.1517
200185	KRTCAP2	GSM4909301	Human	Breast	IDC	3.88e-99	1.19e+00	0.1577
200185	KRTCAP2	GSM4909302	Human	Breast	IDC	3.16e-05	3.11e-01	0.1545
200185	KRTCAP2	GSM4909306	Human	Breast	IDC	5.27e-07	3.41e-01	0.1564
200185	KRTCAP2	GSM4909307	Human	Breast	IDC	3.10e-04	3.08e-01	0.1569
200185	KRTCAP2	GSM4909308	Human	Breast	IDC	3.96e-10	4.36e-01	0.158
200185	KRTCAP2	GSM4909309	Human	Breast	IDC	6.60e-05	3.00e-01	0.0483
200185	KRTCAP2	GSM4909311	Human	Breast	IDC	4.67e-45	3.90e-01	0.1534
200185	KRTCAP2	GSM4909312	Human	Breast	IDC	6.19e-27	5.14e-01	0.1552
200185	KRTCAP2	GSM4909313	Human	Breast	IDC	1.46e-14	5.04e-01	0.0391
200185	KRTCAP2	GSM4909319	Human	Breast	IDC	8.06e-46	6.44e-02	0.1563
200185	KRTCAP2	GSM4909320	Human	Breast	IDC	2.06e-12	4.95e-01	0.1575
200185	KRTCAP2	GSM4909321	Human	Breast	IDC	1.34e-23	3.07e-01	0.1559
200185	KRTCAP2	brca2	Human	Breast	Precancer	2.08e-07	3.02e-01	-0.024
200185	KRTCAP2	M2	Human	Breast	IDC	1.64e-02	1.23e-01	0.21
200185	KRTCAP2	NCCBC14	Human	Breast	DCIS	1.61e-05	-2.08e-02	0.2021
200185	KRTCAP2	NCCBC2	Human	Breast	DCIS	2.65e-05	-1.55e-01	0.1554

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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
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:00064876	Esophagus	HGIN	protein N-linked glycosylation	17/2587	65/18723	6.04e-03	4.87e-02	17
GO:000648714	Esophagus	ESCC	protein N-linked glycosylation	51/8552	65/18723	6.41e-08	1.13e-06	51
GO:00091002	Esophagus	ESCC	glycoprotein metabolic process	226/8552	387/18723	2.64e-07	3.94e-06	226
GO:00700854	Esophagus	ESCC	glycosylation	144/8552	240/18723	5.12e-06	5.38e-05	144
GO:00064865	Esophagus	ESCC	protein glycosylation	135/8552	226/18723	1.36e-05	1.24e-04	135
GO:00434135	Esophagus	ESCC	macromolecule glycosylation	135/8552	226/18723	1.36e-05	1.24e-04	135
GO:00091012	Esophagus	ESCC	glycoprotein biosynthetic process	181/8552	317/18723	2.54e-05	2.15e-04	181
GO:00064873	Liver	Cirrhotic	protein N-linked glycosylation	30/4634	65/18723	1.40e-04	1.36e-03	30
GO:000648711	Liver	HCC	protein N-linked glycosylation	48/7958	65/18723	2.85e-07	5.00e-06	48
GO:00064862	Liver	HCC	protein glycosylation	122/7958	226/18723	3.11e-04	2.21e-03	122
GO:00434132	Liver	HCC	macromolecule glycosylation	122/7958	226/18723	3.11e-04	2.21e-03	122
GO:00700852	Liver	HCC	glycosylation	128/7958	240/18723	4.35e-04	2.92e-03	128
GO:0009100	Liver	HCC	glycoprotein metabolic process	193/7958	387/18723	1.89e-03	9.62e-03	193
GO:00064863	Lung	AIS	protein glycosylation	35/1849	226/18723	4.93e-03	4.27e-02	35
GO:00434133	Lung	AIS	macromolecule glycosylation	35/1849	226/18723	4.93e-03	4.27e-02	35
GO:00064875	Oral cavity	OSCC	protein N-linked glycosylation	44/7305	65/18723	2.63e-06	3.26e-05	44
GO:00091001	Oral cavity	OSCC	glycoprotein metabolic process	185/7305	387/18723	2.37e-04	1.54e-03	185
GO:00091011	Oral cavity	OSCC	glycoprotein biosynthetic process	151/7305	317/18723	1.01e-03	5.26e-03	151
GO:00064864	Oral cavity	OSCC	protein glycosylation	111/7305	226/18723	1.22e-03	6.10e-03	111
GO:00434134	Oral cavity	OSCC	macromolecule glycosylation	111/7305	226/18723	1.22e-03	6.10e-03	111

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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

KRTCAP2

insertion

In_Frame_Ins

novel

c.402_403insGCTATGGACTCACGTCTGCCTCCTGGAAGCCAGCGGCACCCTCCT

p.Ile134_Asn135insAlaMetAspSerArgLeuProProGlySerGlnArgHisProPro

p.I134_N135insAMDSRLPPGSQRHPP

Q8N6L1

protein_coding

TCGA-A2-A0EO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

KRTCAP2

insertion

Frame_Shift_Ins

novel

c.365_366insTTGG

p.Cys123TrpfsTer48

p.C123Wfs*48

Q8N6L1

protein_coding

TCGA-A8-A09E-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

KRTCAP2

SNV

Missense_Mutation

c.463N>G

p.Thr155Ala

p.T155A

Q8N6L1

protein_coding

tolerated(0.26)

benign(0.114)

TCGA-AA-3713-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Chemotherapy

5-fluorouracil

KRTCAP2

SNV

Missense_Mutation

rs372181365

c.350N>A

p.Arg117Gln

p.R117Q

Q8N6L1

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-EI-6882-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

KRTCAP2

SNV

Missense_Mutation

c.255G>T

p.Glu85Asp

p.E85D

Q8N6L1

protein_coding

deleterious(0.01)

probably_damaging(0.992)

TCGA-AP-A056-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

KRTCAP2

SNV

Missense_Mutation

c.482N>T

p.Arg161Ile

p.R161I

Q8N6L1

protein_coding

deleterious(0)

possibly_damaging(0.758)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

KRTCAP2

SNV

Missense_Mutation

c.482G>A

p.Arg161Lys

p.R161K

Q8N6L1

protein_coding

tolerated(0.43)

benign(0.017)

TCGA-B5-A0JY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

KRTCAP2

SNV

Missense_Mutation

rs768462233

c.212N>T

p.Ser71Leu

p.S71L

Q8N6L1

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-D1-A17B-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

KRTCAP2

SNV

Missense_Mutation

c.288N>T

p.Lys96Asn

p.K96N

Q8N6L1

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-FI-A2EW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatinum

KRTCAP2

SNV

Missense_Mutation

c.275N>T

p.Gly92Val

p.G92V

Q8N6L1

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-DD-A3A9-01

Liver

liver hepatocellular 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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