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: KIDINS220

Gene summary for KIDINS220

Gene summary.

Gene information	Species	Human
	Gene symbol	KIDINS220
	Gene ID	57498
	Gene name	kinase D interacting substrate 220
	Gene Alias	ARMS
	Cytomap	2p25.1
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	Q9ULH0

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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
57498	KIDINS220	LN46	Human	Oral cavity	OSCC	2.19e-05	2.48e-01	0.1666
57498	KIDINS220	EOLP-1	Human	Oral cavity	EOLP	1.22e-07	2.56e-01	-0.0202
57498	KIDINS220	NEOLP-2	Human	Oral cavity	NEOLP	1.72e-03	1.85e-01	-0.0196
57498	KIDINS220	NEOLP-3	Human	Oral cavity	NEOLP	6.59e-03	2.25e-01	-0.0191
57498	KIDINS220	SYSMH1	Human	Oral cavity	OSCC	6.78e-10	3.40e-01	0.1127
57498	KIDINS220	SYSMH2	Human	Oral cavity	OSCC	4.79e-09	3.31e-01	0.2326
57498	KIDINS220	SYSMH3	Human	Oral cavity	OSCC	3.21e-14	5.04e-01	0.2442
57498	KIDINS220	SYSMH5	Human	Oral cavity	OSCC	8.82e-03	1.25e-01	0.0647
57498	KIDINS220	SYSMH6	Human	Oral cavity	OSCC	6.36e-06	1.60e-01	0.1275
57498	KIDINS220	HTA12-23-1	Human	Pancreas	PDAC	2.85e-03	6.17e-01	0.3405
57498	KIDINS220	HTA12-25-1	Human	Pancreas	PDAC	5.95e-03	5.23e-01	0.313
57498	KIDINS220	HTA12-26-1	Human	Pancreas	PDAC	1.42e-12	7.26e-01	0.3728
57498	KIDINS220	HTA12-29-1	Human	Pancreas	PDAC	2.16e-31	7.58e-01	0.3722
57498	KIDINS220	GSM5252137_BPH556PrGA2_Fcol	Human	Prostate	BPH	4.25e-02	2.97e-01	-0.23
57498	KIDINS220	052095_1628-all-cells	Human	Prostate	BPH	3.32e-09	3.20e-01	0.1032
57498	KIDINS220	052097_1595-all-cells	Human	Prostate	BPH	2.25e-02	2.51e-01	0.0972
57498	KIDINS220	052099_1652-all-cells	Human	Prostate	BPH	2.20e-03	2.27e-01	0.1038
57498	KIDINS220	Dong_P1	Human	Prostate	Tumor	2.36e-15	1.84e-02	0.035
57498	KIDINS220	Dong_P3	Human	Prostate	Tumor	1.91e-06	1.15e-01	0.0278
57498	KIDINS220	Dong_P5	Human	Prostate	Tumor	6.52e-15	3.89e-02	0.053

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:000170119	Esophagus	ESCC	in utero embryonic development	243/8552	367/18723	1.00e-15	6.86e-14	243
GO:003134616	Esophagus	ESCC	positive regulation of cell projection organization	201/8552	353/18723	1.19e-05	1.11e-04	201
GO:199009017	Esophagus	ESCC	cellular response to nerve growth factor stimulus	38/8552	53/18723	1.10e-04	7.69e-04	38
GO:199008916	Esophagus	ESCC	response to nerve growth factor	39/8552	56/18723	2.44e-04	1.51e-03	39
GO:001097516	Esophagus	ESCC	regulation of neuron projection development	240/8552	445/18723	2.48e-04	1.53e-03	240
GO:00109764	Esophagus	ESCC	positive regulation of neuron projection development	91/8552	163/18723	5.72e-03	2.13e-02	91
GO:001635816	Esophagus	ESCC	dendrite development	130/8552	243/18723	8.33e-03	2.95e-02	130
GO:19900906	Liver	NAFLD	cellular response to nerve growth factor stimulus	16/1882	53/18723	4.07e-05	9.99e-04	16
GO:19900895	Liver	NAFLD	response to nerve growth factor	16/1882	56/18723	8.53e-05	1.72e-03	16
GO:00163585	Liver	NAFLD	dendrite development	43/1882	243/18723	1.70e-04	3.07e-03	43
GO:00313465	Liver	NAFLD	positive regulation of cell projection organization	57/1882	353/18723	2.19e-04	3.73e-03	57
GO:00488133	Liver	NAFLD	dendrite morphogenesis	29/1882	146/18723	2.63e-04	4.26e-03	29
GO:0038179	Liver	NAFLD	neurotrophin signaling pathway	11/1882	36/18723	5.73e-04	7.66e-03	11
GO:00109755	Liver	NAFLD	regulation of neuron projection development	64/1882	445/18723	2.12e-03	2.08e-02	64
GO:0038180	Liver	NAFLD	nerve growth factor signaling pathway	5/1882	12/18723	4.41e-03	3.57e-02	5
GO:00017015	Liver	Cirrhotic	in utero embryonic development	134/4634	367/18723	2.78e-07	6.86e-06	134
GO:199009011	Liver	Cirrhotic	cellular response to nerve growth factor stimulus	24/4634	53/18723	8.86e-04	6.37e-03	24
GO:199008911	Liver	Cirrhotic	response to nerve growth factor	25/4634	56/18723	9.03e-04	6.46e-03	25
GO:000170111	Liver	HCC	in utero embryonic development	204/7958	367/18723	2.44e-07	4.30e-06	204
GO:003134611	Liver	HCC	positive regulation of cell projection organization	193/7958	353/18723	2.28e-06	3.08e-05	193

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0472225	Esophagus	ESCC	Neurotrophin signaling pathway	80/4205	119/8465	7.33e-05	3.07e-04	1.57e-04	80
hsa04722111	Esophagus	ESCC	Neurotrophin signaling pathway	80/4205	119/8465	7.33e-05	3.07e-04	1.57e-04	80
hsa0472210	Liver	HCC	Neurotrophin signaling pathway	74/4020	119/8465	8.27e-04	3.26e-03	1.81e-03	74
hsa0472211	Liver	HCC	Neurotrophin signaling pathway	74/4020	119/8465	8.27e-04	3.26e-03	1.81e-03	74
hsa0472220	Oral cavity	OSCC	Neurotrophin signaling pathway	74/3704	119/8465	3.55e-05	1.49e-04	7.58e-05	74
hsa04722110	Oral cavity	OSCC	Neurotrophin signaling pathway	74/3704	119/8465	3.55e-05	1.49e-04	7.58e-05	74
hsa0472242	Oral cavity	EOLP	Neurotrophin signaling pathway	36/1218	119/8465	6.23e-06	3.87e-05	2.28e-05	36
hsa0472252	Oral cavity	EOLP	Neurotrophin signaling pathway	36/1218	119/8465	6.23e-06	3.87e-05	2.28e-05	36
hsa0472261	Oral cavity	NEOLP	Neurotrophin signaling pathway	31/1112	119/8465	1.06e-04	7.67e-04	4.82e-04	31
hsa0472271	Oral cavity	NEOLP	Neurotrophin signaling pathway	31/1112	119/8465	1.06e-04	7.67e-04	4.82e-04	31
hsa0472218	Prostate	BPH	Neurotrophin signaling pathway	38/1718	119/8465	1.76e-03	7.16e-03	4.43e-03	38
hsa0472219	Prostate	BPH	Neurotrophin signaling pathway	38/1718	119/8465	1.76e-03	7.16e-03	4.43e-03	38
hsa0472223	Prostate	Tumor	Neurotrophin signaling pathway	39/1791	119/8465	2.01e-03	8.10e-03	5.02e-03	39
hsa0472233	Prostate	Tumor	Neurotrophin signaling pathway	39/1791	119/8465	2.01e-03	8.10e-03	5.02e-03	39

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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

KIDINS220

SNV

Missense_Mutation

c.1243C>A

p.Gln415Lys

p.Q415K

Q9ULH0

protein_coding

deleterious(0.01)

probably_damaging(0.983)

TCGA-A1-A0SI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

KIDINS220

SNV

Missense_Mutation

novel

c.117N>C

p.Gln39His

p.Q39H

Q9ULH0

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-A7-A0DA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

KIDINS220

SNV

Missense_Mutation

c.5144N>T

p.Pro1715Leu

p.P1715L

Q9ULH0

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.962)

TCGA-A8-A07I-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

KIDINS220

SNV

Missense_Mutation

novel

c.671A>G

p.Lys224Arg

p.K224R

Q9ULH0

protein_coding

deleterious(0.02)

probably_damaging(0.999)

TCGA-AC-A2QI-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

KIDINS220

SNV

Missense_Mutation

c.3287N>A

p.Ser1096Asn

p.S1096N

Q9ULH0

protein_coding

tolerated(0.17)

benign(0.007)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

KIDINS220

SNV

Missense_Mutation

rs749886554

c.5215C>T

p.Arg1739Cys

p.R1739C

Q9ULH0

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.794)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KIDINS220

SNV

Missense_Mutation

c.1913G>T

p.Arg638Leu

p.R638L

Q9ULH0

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-C8-A1HN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

KIDINS220

SNV

Missense_Mutation

c.3796N>C

p.Trp1266Arg

p.W1266R

Q9ULH0

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-D8-A1X9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

adriamycin+cyclophosphamide

KIDINS220

SNV

Missense_Mutation

rs772740508

c.2503N>T

p.Arg835Cys

p.R835C

Q9ULH0

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-E9-A1RF-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

KIDINS220

insertion

Frame_Shift_Ins

novel

c.3154_3155insCTTTTCCCCTTTTT

p.Val1052AlafsTer6

p.V1052Afs*6

Q9ULH0

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

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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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