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: IL15RA

Gene summary for IL15RA

Gene summary.

Gene information	Species	Human
	Gene symbol	IL15RA
	Gene ID	3601
	Gene name	interleukin 15 receptor subunit alpha
	Gene Alias	CD215
	Cytomap	10p15.1
	Gene Type	protein-coding
	GO ID	GO:0001775
	UniProtAcc	Q13261

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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
3601	IL15RA	LZE4T	Human	Esophagus	ESCC	1.35e-02	9.26e-02	0.0811
3601	IL15RA	LZE8T	Human	Esophagus	ESCC	4.38e-02	7.10e-02	0.067
3601	IL15RA	LZE20T	Human	Esophagus	ESCC	6.37e-03	8.07e-02	0.0662
3601	IL15RA	LZE24T	Human	Esophagus	ESCC	5.12e-10	2.97e-01	0.0596
3601	IL15RA	LZE21T	Human	Esophagus	ESCC	1.45e-02	1.92e-01	0.0655
3601	IL15RA	P2T-E	Human	Esophagus	ESCC	1.64e-13	2.61e-01	0.1177
3601	IL15RA	P4T-E	Human	Esophagus	ESCC	3.29e-03	1.18e-01	0.1323
3601	IL15RA	P5T-E	Human	Esophagus	ESCC	1.25e-09	2.49e-01	0.1327
3601	IL15RA	P8T-E	Human	Esophagus	ESCC	5.04e-15	2.33e-01	0.0889
3601	IL15RA	P9T-E	Human	Esophagus	ESCC	1.17e-09	2.64e-01	0.1131
3601	IL15RA	P11T-E	Human	Esophagus	ESCC	2.61e-06	2.97e-01	0.1426
3601	IL15RA	P16T-E	Human	Esophagus	ESCC	9.28e-05	1.81e-02	0.1153
3601	IL15RA	P17T-E	Human	Esophagus	ESCC	3.04e-03	2.15e-01	0.1278
3601	IL15RA	P20T-E	Human	Esophagus	ESCC	2.11e-08	2.06e-01	0.1124
3601	IL15RA	P21T-E	Human	Esophagus	ESCC	4.93e-27	6.05e-01	0.1617
3601	IL15RA	P23T-E	Human	Esophagus	ESCC	1.16e-12	3.49e-01	0.108
3601	IL15RA	P24T-E	Human	Esophagus	ESCC	3.21e-25	7.49e-01	0.1287
3601	IL15RA	P26T-E	Human	Esophagus	ESCC	6.03e-21	2.16e-01	0.1276
3601	IL15RA	P27T-E	Human	Esophagus	ESCC	3.71e-14	1.96e-01	0.1055
3601	IL15RA	P31T-E	Human	Esophagus	ESCC	2.30e-15	2.74e-01	0.1251

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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

∗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:1903706110	Esophagus	ESCC	regulation of hemopoiesis	201/8552	367/18723	2.60e-04	1.58e-03	201
GO:19021076	Esophagus	ESCC	positive regulation of leukocyte differentiation	93/8552	157/18723	4.20e-04	2.39e-03	93
GO:19037086	Esophagus	ESCC	positive regulation of hemopoiesis	93/8552	157/18723	4.20e-04	2.39e-03	93
GO:19031317	Esophagus	ESCC	mononuclear cell differentiation	226/8552	426/18723	1.20e-03	5.88e-03	226
GO:190210510	Esophagus	ESCC	regulation of leukocyte differentiation	152/8552	279/18723	1.82e-03	8.35e-03	152
GO:00456213	Esophagus	ESCC	positive regulation of lymphocyte differentiation	61/8552	104/18723	5.22e-03	1.97e-02	61
GO:00300984	Esophagus	ESCC	lymphocyte differentiation	192/8552	374/18723	1.52e-02	4.93e-02	192
GO:0050764	Liver	NAFLD	regulation of phagocytosis	19/1882	95/18723	2.61e-03	2.41e-02	19
GO:0050766	Liver	NAFLD	positive regulation of phagocytosis	14/1882	66/18723	5.28e-03	4.08e-02	14
GO:19031316	Oral cavity	OSCC	mononuclear cell differentiation	210/7305	426/18723	8.44e-06	9.02e-05	210
GO:190370618	Oral cavity	OSCC	regulation of hemopoiesis	180/7305	367/18723	5.16e-05	4.30e-04	180
GO:00192214	Oral cavity	OSCC	cytokine-mediated signaling pathway	222/7305	472/18723	2.02e-04	1.35e-03	222
GO:00300983	Oral cavity	OSCC	lymphocyte differentiation	179/7305	374/18723	2.74e-04	1.74e-03	179
GO:19021059	Oral cavity	OSCC	regulation of leukocyte differentiation	136/7305	279/18723	5.53e-04	3.21e-03	136
GO:19021075	Oral cavity	OSCC	positive regulation of leukocyte differentiation	77/7305	157/18723	6.55e-03	2.43e-02	77
GO:19037085	Oral cavity	OSCC	positive regulation of hemopoiesis	77/7305	157/18723	6.55e-03	2.43e-02	77
GO:00456194	Oral cavity	OSCC	regulation of lymphocyte differentiation	83/7305	174/18723	1.18e-02	4.00e-02	83
GO:00507643	Oral cavity	OSCC	regulation of phagocytosis	48/7305	95/18723	1.47e-02	4.77e-02	48
GO:190370619	Oral cavity	LP	regulation of hemopoiesis	111/4623	367/18723	8.48e-03	4.60e-02	111
GO:001922122	Oral cavity	NEOLP	cytokine-mediated signaling pathway	88/2005	472/18723	1.37e-07	4.80e-06	88

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05166211	Esophagus	ESCC	Human T-cell leukemia virus 1 infection	164/4205	222/8465	8.13e-14	2.09e-12	1.07e-12	164
hsa05166310	Esophagus	ESCC	Human T-cell leukemia virus 1 infection	164/4205	222/8465	8.13e-14	2.09e-12	1.07e-12	164
hsa0516622	Liver	HCC	Human T-cell leukemia virus 1 infection	139/4020	222/8465	3.17e-06	2.79e-05	1.55e-05	139
hsa0516632	Liver	HCC	Human T-cell leukemia virus 1 infection	139/4020	222/8465	3.17e-06	2.79e-05	1.55e-05	139
hsa0516630	Oral cavity	OSCC	Human T-cell leukemia virus 1 infection	150/3704	222/8465	3.68e-13	7.26e-12	3.70e-12	150
hsa05166113	Oral cavity	OSCC	Human T-cell leukemia virus 1 infection	150/3704	222/8465	3.68e-13	7.26e-12	3.70e-12	150
hsa05166210	Oral cavity	LP	Human T-cell leukemia virus 1 infection	100/2418	222/8465	8.94e-08	1.29e-06	8.35e-07	100
hsa0516638	Oral cavity	LP	Human T-cell leukemia virus 1 infection	100/2418	222/8465	8.94e-08	1.29e-06	8.35e-07	100
hsa0516662	Oral cavity	NEOLP	Human T-cell leukemia virus 1 infection	50/1112	222/8465	6.91e-05	5.23e-04	3.29e-04	50
hsa0516672	Oral cavity	NEOLP	Human T-cell leukemia virus 1 infection	50/1112	222/8465	6.91e-05	5.23e-04	3.29e-04	50

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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
IL15	IL15RA_IL2RB	IL15_IL15RA_IL2RB	IL2	HNSCC	OSCC

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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

IL15RA

SNV

Missense_Mutation

rs201243364

c.836C>T

p.Pro279Leu

p.P279L

protein_coding

deleterious_low_confidence(0.01)

benign(0.109)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

IL15RA

SNV

Missense_Mutation

rs781024557

c.787C>G

p.Gln263Glu

p.Q263E

protein_coding

tolerated_low_confidence(0.08)

possibly_damaging(0.679)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

IL15RA

SNV

Missense_Mutation

c.935N>A

p.Cys312Tyr

p.C312Y

protein_coding

tolerated_low_confidence(0.24)

benign(0.048)

TCGA-A6-2671-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Other, specify in notesProtocol AMG 20060464

study

IL15RA

SNV

Missense_Mutation

novel

c.801G>T

p.Lys267Asn

p.K267N

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.679)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

IL15RA

insertion

Frame_Shift_Ins

novel

c.621_622insT

p.Leu208SerfsTer48

p.L208Sfs*48

protein_coding

TCGA-AA-3949-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

IL15RA

SNV

Missense_Mutation

rs773161996

c.424N>T

p.Arg142Trp

p.R142W

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.999)

TCGA-A5-A0G1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

IL15RA

SNV

Missense_Mutation

novel

c.367N>G

p.Met123Val

p.M123V

protein_coding

tolerated_low_confidence(0.57)

benign(0.003)

TCGA-AX-A0IZ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

IL15RA

SNV

Missense_Mutation

novel

c.494A>G

p.Lys165Arg

p.K165R

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.845)

TCGA-B5-A1MX-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Hormone Therapy

megace

IL15RA

SNV

Missense_Mutation

novel

c.923C>A

p.Ser308Tyr

p.S308Y

protein_coding

tolerated_low_confidence(1)

probably_damaging(0.953)

TCGA-EO-A22R-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

IL15RA

SNV

Missense_Mutation

rs775877874

c.916N>A

p.Ala306Thr

p.A306T

protein_coding

deleterious_low_confidence(0.03)

probably_damaging(0.998)

TCGA-EY-A1GR-01

Endometrium

uterine corpus endometrioid 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
3601	IL15RA	DRUGGABLE GENOME, CELL SURFACE	agonist	178101678	INTERLEUKIN 15, RECOMBINANT NON-GLYCOSYLATED
3601	IL15RA	DRUGGABLE GENOME, CELL SURFACE		BNZ-1
3601	IL15RA	DRUGGABLE GENOME, CELL SURFACE		ALT-803	ALT-803

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