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: NKTR

Gene summary for NKTR

Gene summary.

Gene information	Species	Human
	Gene symbol	NKTR
	Gene ID	4820
	Gene name	natural killer cell triggering receptor
	Gene Alias	p104
	Cytomap	3p22.1
	Gene Type	protein-coding
	GO ID	GO:0000413
	UniProtAcc	A0A024R2N6

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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
4820	NKTR	GSM4909281	Human	Breast	IDC	7.16e-09	3.92e-01	0.21
4820	NKTR	GSM4909292	Human	Breast	IDC	4.81e-03	6.62e-01	0.1236
4820	NKTR	GSM4909294	Human	Breast	IDC	3.90e-02	-2.55e-01	0.2022
4820	NKTR	GSM4909296	Human	Breast	IDC	1.26e-12	-3.20e-01	0.1524
4820	NKTR	GSM4909297	Human	Breast	IDC	3.83e-08	-2.38e-01	0.1517
4820	NKTR	GSM4909309	Human	Breast	IDC	3.74e-02	-1.56e-01	0.0483
4820	NKTR	GSM4909311	Human	Breast	IDC	1.03e-23	-3.11e-01	0.1534
4820	NKTR	GSM4909312	Human	Breast	IDC	6.48e-08	-1.82e-01	0.1552
4820	NKTR	GSM4909319	Human	Breast	IDC	1.12e-23	-3.94e-01	0.1563
4820	NKTR	GSM4909320	Human	Breast	IDC	3.22e-08	-3.43e-01	0.1575
4820	NKTR	GSM4909321	Human	Breast	IDC	9.68e-13	-2.70e-01	0.1559
4820	NKTR	M1	Human	Breast	IDC	2.23e-06	5.13e-01	0.1577
4820	NKTR	NCCBC14	Human	Breast	DCIS	3.20e-09	-2.07e-01	0.2021
4820	NKTR	NCCBC5	Human	Breast	DCIS	6.36e-12	-3.21e-01	0.2046
4820	NKTR	P1	Human	Breast	IDC	1.99e-21	2.88e-01	0.1527
4820	NKTR	P2	Human	Breast	IDC	1.35e-02	-2.82e-01	0.21
4820	NKTR	DCIS2	Human	Breast	DCIS	4.85e-53	4.10e-01	0.0085
4820	NKTR	HTA11_3410_2000001011	Human	Colorectum	AD	5.08e-38	-9.77e-01	0.0155
4820	NKTR	HTA11_2487_2000001011	Human	Colorectum	SER	1.88e-21	-9.09e-01	-0.1808
4820	NKTR	HTA11_2951_2000001011	Human	Colorectum	AD	2.73e-08	-1.08e+00	0.0216

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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
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
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	CRC
Stomach	GC
Stomach	CAG with IM
Stomach	CSG
Stomach	CAG

∗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:000645713	Breast	IDC	protein folding	47/1434	212/18723	2.31e-11	3.86e-09	47
GO:001820812	Breast	IDC	peptidyl-proline modification	13/1434	58/18723	3.59e-04	5.18e-03	13
GO:000645723	Breast	DCIS	protein folding	47/1390	212/18723	7.84e-12	1.53e-09	47
GO:001820821	Breast	DCIS	peptidyl-proline modification	13/1390	58/18723	2.65e-04	4.03e-03	13
GO:0006457	Colorectum	AD	protein folding	73/3918	212/18723	3.24e-06	9.10e-05	73
GO:00064571	Colorectum	SER	protein folding	54/2897	212/18723	1.04e-04	2.18e-03	54
GO:00064572	Colorectum	MSS	protein folding	71/3467	212/18723	1.25e-07	5.91e-06	71
GO:00064574	Colorectum	FAP	protein folding	44/2622	212/18723	4.36e-03	2.98e-02	44
GO:000645715	Endometrium	EEC	protein folding	63/2168	212/18723	6.82e-13	1.40e-10	63
GO:000041311	Endometrium	EEC	protein peptidyl-prolyl isomerization	14/2168	42/18723	1.69e-04	2.10e-03	14
GO:001820813	Endometrium	EEC	peptidyl-proline modification	17/2168	58/18723	2.11e-04	2.54e-03	17
GO:000645720	Esophagus	HGIN	protein folding	75/2587	212/18723	1.61e-15	3.86e-13	75
GO:00182089	Esophagus	HGIN	peptidyl-proline modification	17/2587	58/18723	1.64e-03	1.82e-02	17
GO:00004135	Esophagus	HGIN	protein peptidyl-prolyl isomerization	13/2587	42/18723	3.32e-03	3.12e-02	13
GO:0006457110	Esophagus	ESCC	protein folding	163/8552	212/18723	1.13e-20	1.74e-18	163
GO:001820816	Esophagus	ESCC	peptidyl-proline modification	46/8552	58/18723	1.59e-07	2.51e-06	46
GO:000041313	Esophagus	ESCC	protein peptidyl-prolyl isomerization	32/8552	42/18723	5.52e-05	4.27e-04	32
GO:00064577	Liver	Cirrhotic	protein folding	114/4634	212/18723	9.23e-20	2.31e-17	114
GO:00182084	Liver	Cirrhotic	peptidyl-proline modification	26/4634	58/18723	6.65e-04	5.04e-03	26
GO:00004132	Liver	Cirrhotic	protein peptidyl-prolyl isomerization	19/4634	42/18723	3.00e-03	1.71e-02	19

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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

NKTR

SNV

Missense_Mutation

c.2665T>A

p.Ser889Thr

p.S889T

P30414

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.985)

TCGA-A8-A09M-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

paclitaxel

NKTR

SNV

Missense_Mutation

c.2900N>T

p.Ser967Leu

p.S967L

P30414

protein_coding

tolerated_low_confidence(0.3)

benign(0)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NKTR

SNV

Missense_Mutation

rs144598783

c.3817N>T

p.Arg1273Trp

p.R1273W

P30414

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.999)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NKTR

SNV

Missense_Mutation

c.196N>T

p.Arg66Cys

p.R66C

P30414

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NKTR

SNV

Missense_Mutation

c.1618N>G

p.Lys540Glu

p.K540E

P30414

protein_coding

deleterious_low_confidence(0.05)

benign(0.073)

TCGA-C8-A27B-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

NKTR

SNV

Missense_Mutation

c.112N>G

p.Asn38Asp

p.N38D

P30414

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.999)

TCGA-E2-A14O-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

arimidex

NKTR

SNV

Missense_Mutation

novel

c.3427G>C

p.Glu1143Gln

p.E1143Q

P30414

protein_coding

tolerated_low_confidence(0.05)

benign(0.288)

TCGA-EW-A3E8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

anastrozole

NKTR

insertion

In_Frame_Ins

novel

c.730_731insTATTAT

p.Ser244delinsIleLeuCys

p.S244delinsILC

P30414

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

NKTR

insertion

Frame_Shift_Ins

novel

c.731_732insCAATTCTTTTTTTTTTTTT

p.Ser245AsnfsTer13

p.S245Nfs*13

P30414

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

NKTR

insertion

Frame_Shift_Ins

novel

c.3392_3393insC

p.Cys1132LeufsTer4

p.C1132Lfs*4

P30414

protein_coding

TCGA-AR-A256-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

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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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