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: KRI1

Gene summary for KRI1

Gene summary.

Gene information	Species	Human
	Gene symbol	KRI1
	Gene ID	65095
	Gene name	KRI1 homolog
	Gene Alias	KRI1
	Cytomap	19p13.2
	Gene Type	protein-coding
	GO ID	GO:0000447
	UniProtAcc	Q8N9T8

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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
65095	KRI1	LZE2T	Human	Esophagus	ESCC	1.38e-02	4.31e-01	0.082
65095	KRI1	LZE4T	Human	Esophagus	ESCC	1.46e-14	4.39e-01	0.0811
65095	KRI1	LZE7T	Human	Esophagus	ESCC	2.46e-11	5.90e-01	0.0667
65095	KRI1	LZE8T	Human	Esophagus	ESCC	1.29e-08	2.83e-01	0.067
65095	KRI1	LZE20T	Human	Esophagus	ESCC	2.22e-04	8.11e-02	0.0662
65095	KRI1	LZE24T	Human	Esophagus	ESCC	1.21e-16	4.45e-01	0.0596
65095	KRI1	LZE21T	Human	Esophagus	ESCC	2.00e-07	4.45e-01	0.0655
65095	KRI1	LZE6T	Human	Esophagus	ESCC	3.81e-04	1.52e-01	0.0845
65095	KRI1	P1T-E	Human	Esophagus	ESCC	5.99e-10	6.80e-01	0.0875
65095	KRI1	P2T-E	Human	Esophagus	ESCC	1.50e-16	3.40e-01	0.1177
65095	KRI1	P4T-E	Human	Esophagus	ESCC	6.97e-30	6.72e-01	0.1323
65095	KRI1	P5T-E	Human	Esophagus	ESCC	1.25e-17	3.60e-01	0.1327
65095	KRI1	P8T-E	Human	Esophagus	ESCC	5.82e-29	5.11e-01	0.0889
65095	KRI1	P9T-E	Human	Esophagus	ESCC	1.46e-27	6.37e-01	0.1131
65095	KRI1	P10T-E	Human	Esophagus	ESCC	3.56e-33	5.93e-01	0.116
65095	KRI1	P11T-E	Human	Esophagus	ESCC	2.95e-06	2.79e-01	0.1426
65095	KRI1	P12T-E	Human	Esophagus	ESCC	8.46e-41	7.44e-01	0.1122
65095	KRI1	P15T-E	Human	Esophagus	ESCC	6.50e-21	5.08e-01	0.1149
65095	KRI1	P16T-E	Human	Esophagus	ESCC	3.61e-22	2.82e-01	0.1153
65095	KRI1	P17T-E	Human	Esophagus	ESCC	4.35e-13	4.26e-01	0.1278

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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:009050111	Oral cavity	LP	RNA phosphodiester bond hydrolysis	63/4623	152/18723	3.88e-06	8.13e-05	63
GO:00004691	Oral cavity	LP	cleavage involved in rRNA processing	18/4623	27/18723	4.92e-06	9.94e-05	18
GO:000046211	Oral cavity	LP	maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	22/4623	37/18723	7.11e-06	1.37e-04	22
GO:00903051	Oral cavity	LP	nucleic acid phosphodiester bond hydrolysis	92/4623	261/18723	8.07e-05	1.04e-03	92
GO:00004661	Oral cavity	LP	maturation of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	14/4623	24/18723	4.52e-04	4.30e-03	14
GO:00004781	Oral cavity	LP	endonucleolytic cleavage involved in rRNA processing	9/4623	15/18723	3.82e-03	2.48e-02	9
GO:00004791	Oral cavity	LP	endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	9/4623	15/18723	3.82e-03	2.48e-02	9
GO:00905021	Oral cavity	LP	RNA phosphodiester bond hydrolysis, endonucleolytic	31/4623	82/18723	5.66e-03	3.41e-02	31
GO:002261319	Prostate	Tumor	ribonucleoprotein complex biogenesis	159/3246	463/18723	3.17e-19	1.52e-16	159
GO:004225419	Prostate	Tumor	ribosome biogenesis	96/3246	299/18723	2.76e-10	1.51e-08	96
GO:000636417	Prostate	Tumor	rRNA processing	69/3246	225/18723	5.98e-07	1.26e-05	69
GO:001607217	Prostate	Tumor	rRNA metabolic process	71/3246	236/18723	9.17e-07	1.79e-05	71
GO:004227419	Prostate	Tumor	ribosomal small subunit biogenesis	26/3246	73/18723	1.36e-04	1.26e-03	26
GO:003447013	Prostate	Tumor	ncRNA processing	94/3246	395/18723	6.02e-04	4.31e-03	94
GO:002261329	Skin	cSCC	ribonucleoprotein complex biogenesis	302/4864	463/18723	5.13e-72	3.22e-68	302
GO:004225428	Skin	cSCC	ribosome biogenesis	206/4864	299/18723	3.33e-55	1.04e-51	206
GO:000636424	Skin	cSCC	rRNA processing	156/4864	225/18723	1.42e-42	1.48e-39	156
GO:001607224	Skin	cSCC	rRNA metabolic process	158/4864	236/18723	4.06e-40	2.83e-37	158
GO:003447017	Skin	cSCC	ncRNA processing	215/4864	395/18723	6.83e-34	4.28e-31	215
GO:003466013	Skin	cSCC	ncRNA metabolic process	234/4864	485/18723	1.37e-26	4.77e-24	234

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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

KRI1

SNV

Missense_Mutation

rs752490810

c.971C>T

p.Ala324Val

p.A324V

Q8N9T8

protein_coding

tolerated(0.08)

benign(0.099)

TCGA-AN-A0FS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

KRI1

SNV

Missense_Mutation

c.193G>A

p.Asp65Asn

p.D65N

Q8N9T8

protein_coding

tolerated(0.09)

probably_damaging(0.996)

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

KRI1

SNV

Missense_Mutation

novel

c.1366C>G

p.Pro456Ala

p.P456A

Q8N9T8

protein_coding

tolerated(0.07)

possibly_damaging(0.76)

TCGA-B6-A0I1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KRI1

SNV

Missense_Mutation

c.1316N>A

p.Gly439Glu

p.G439E

Q8N9T8

protein_coding

deleterious(0.04)

probably_damaging(0.959)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KRI1

insertion

Nonsense_Mutation

novel

c.1555_1556insCTAATAGTCCTAATGACAGTGCTAATAACATTACCTCGCCTCAAAGGT

p.Glu519delinsAlaAsnSerProAsnAspSerAlaAsnAsnIleThrSerProGlnArgTer

p.E519delinsANSPNDSANNITSPQR*

Q8N9T8

protein_coding

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

KRI1

deletion

Frame_Shift_Del

novel

c.792delN

p.Asp264GlufsTer31

p.D264Efs*31

Q8N9T8

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

KRI1

SNV

Missense_Mutation

c.1465N>A

p.Ala489Thr

p.A489T

Q8N9T8

protein_coding

tolerated(0.06)

probably_damaging(0.956)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

KRI1

SNV

Missense_Mutation

novel

c.1363N>A

p.Asp455Asn

p.D455N

Q8N9T8

protein_coding

deleterious(0.01)

probably_damaging(0.975)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

KRI1

SNV

Missense_Mutation

c.1801G>A

p.Ala601Thr

p.A601T

Q8N9T8

protein_coding

tolerated(0.72)

benign(0)

TCGA-AA-3672-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

KRI1

SNV

Missense_Mutation

rs150288571

c.1291G>A

p.Asp431Asn

p.D431N

Q8N9T8

protein_coding

tolerated(0.2)

benign(0.02)

TCGA-AA-A00N-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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