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: HLA-A

Gene summary for HLA-A

Gene summary.

Gene information	Species	Human
	Gene symbol	HLA-A
	Gene ID	3105
	Gene name	major histocompatibility complex, class I, A
	Gene Alias	HLAA
	Cytomap	6p22.1
	Gene Type	protein-coding
	GO ID	GO:0001775
	UniProtAcc	P30443

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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
3105	HLA-A	GSM4909281	Human	Breast	IDC	5.87e-22	6.00e-01	0.21
3105	HLA-A	GSM4909282	Human	Breast	IDC	8.98e-36	6.43e-01	-0.0288
3105	HLA-A	GSM4909285	Human	Breast	IDC	3.33e-18	-4.99e-01	0.21
3105	HLA-A	GSM4909286	Human	Breast	IDC	1.29e-43	-7.86e-01	0.1081
3105	HLA-A	GSM4909287	Human	Breast	IDC	1.69e-13	3.81e-01	0.2057
3105	HLA-A	GSM4909288	Human	Breast	IDC	1.91e-15	5.82e-01	0.0988
3105	HLA-A	GSM4909294	Human	Breast	IDC	2.09e-13	-3.22e-01	0.2022
3105	HLA-A	GSM4909296	Human	Breast	IDC	9.43e-12	-2.33e-01	0.1524
3105	HLA-A	GSM4909297	Human	Breast	IDC	2.91e-18	-5.67e-02	0.1517
3105	HLA-A	GSM4909298	Human	Breast	IDC	1.55e-03	-2.22e-01	0.1551
3105	HLA-A	GSM4909299	Human	Breast	IDC	3.17e-02	3.50e-01	0.035
3105	HLA-A	GSM4909301	Human	Breast	IDC	6.42e-08	-3.49e-01	0.1577
3105	HLA-A	GSM4909304	Human	Breast	IDC	1.10e-32	-7.24e-01	0.1636
3105	HLA-A	GSM4909305	Human	Breast	IDC	7.02e-13	4.96e-01	0.0436
3105	HLA-A	GSM4909307	Human	Breast	IDC	1.02e-06	3.78e-01	0.1569
3105	HLA-A	GSM4909308	Human	Breast	IDC	5.06e-21	5.33e-01	0.158
3105	HLA-A	GSM4909309	Human	Breast	IDC	3.39e-06	3.09e-01	0.0483
3105	HLA-A	GSM4909311	Human	Breast	IDC	1.17e-43	-4.36e-01	0.1534
3105	HLA-A	GSM4909312	Human	Breast	IDC	5.98e-31	-7.09e-01	0.1552
3105	HLA-A	GSM4909315	Human	Breast	IDC	4.58e-51	-9.02e-01	0.21

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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
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
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
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:00480025	Stomach	SIM	antigen processing and presentation of peptide antigen	15/708	62/18723	7.10e-09	9.57e-07	15
GO:00198825	Stomach	SIM	antigen processing and presentation	18/708	106/18723	8.62e-08	7.97e-06	18
GO:00024785	Stomach	SIM	antigen processing and presentation of exogenous peptide antigen	11/708	38/18723	9.90e-08	8.64e-06	11
GO:00198845	Stomach	SIM	antigen processing and presentation of exogenous antigen	12/708	47/18723	1.21e-07	9.98e-06	12
GO:00197305	Stomach	SIM	antimicrobial humoral response	19/708	122/18723	1.58e-07	1.22e-05	19
GO:004578551	Stomach	SIM	positive regulation of cell adhesion	40/708	437/18723	2.47e-07	1.74e-05	40
GO:00224075	Stomach	SIM	regulation of cell-cell adhesion	40/708	448/18723	4.73e-07	3.05e-05	40
GO:00508705	Stomach	SIM	positive regulation of T cell activation	24/708	216/18723	2.41e-06	1.18e-04	24
GO:00198835	Stomach	SIM	antigen processing and presentation of endogenous antigen	8/708	26/18723	3.43e-06	1.60e-04	8
GO:00024835	Stomach	SIM	antigen processing and presentation of endogenous peptide antigen	7/708	19/18723	3.63e-06	1.66e-04	7
GO:00224095	Stomach	SIM	positive regulation of cell-cell adhesion	28/708	284/18723	3.86e-06	1.68e-04	28
GO:19030395	Stomach	SIM	positive regulation of leukocyte cell-cell adhesion	25/708	239/18723	4.46e-06	1.88e-04	25
GO:19030375	Stomach	SIM	regulation of leukocyte cell-cell adhesion	31/708	336/18723	4.73e-06	1.94e-04	31
GO:00071595	Stomach	SIM	leukocyte cell-cell adhesion	33/708	371/18723	5.16e-06	2.08e-04	33
GO:00508635	Stomach	SIM	regulation of T cell activation	29/708	329/18723	2.26e-05	7.00e-04	29
GO:00706614	Stomach	SIM	leukocyte proliferation	28/708	318/18723	3.17e-05	9.35e-04	28
GO:00420984	Stomach	SIM	T cell proliferation	20/708	199/18723	6.96e-05	1.79e-03	20
GO:00019065	Stomach	SIM	cell killing	19/708	188/18723	9.73e-05	2.39e-03	19
GO:00421104	Stomach	SIM	T cell activation	36/708	487/18723	1.05e-04	2.54e-03	36
GO:00069595	Stomach	SIM	humoral immune response	26/708	317/18723	1.91e-04	4.00e-03	26

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0516718	Breast	Precancer	Kaposi sarcoma-associated herpesvirus infection	36/684	194/8465	1.68e-06	2.53e-05	1.94e-05	36
hsa0461218	Breast	Precancer	Antigen processing and presentation	19/684	78/8465	9.61e-06	1.12e-04	8.62e-05	19
hsa0516918	Breast	Precancer	Epstein-Barr virus infection	35/684	202/8465	1.15e-05	1.26e-04	9.64e-05	35
hsa042189	Breast	Precancer	Cellular senescence	29/684	156/8465	1.66e-05	1.69e-04	1.30e-04	29
hsa0414518	Breast	Precancer	Phagosome	27/684	152/8465	7.37e-05	6.85e-04	5.25e-04	27
hsa0541618	Breast	Precancer	Viral myocarditis	14/684	60/8465	2.32e-04	1.98e-03	1.52e-03	14
hsa0516618	Breast	Precancer	Human T-cell leukemia virus 1 infection	33/684	222/8465	4.29e-04	3.31e-03	2.53e-03	33
hsa0516316	Breast	Precancer	Human cytomegalovirus infection	32/684	225/8465	1.13e-03	7.57e-03	5.80e-03	32
hsa052036	Breast	Precancer	Viral carcinogenesis	27/684	204/8465	7.19e-03	4.06e-02	3.11e-02	27
hsa0516719	Breast	Precancer	Kaposi sarcoma-associated herpesvirus infection	36/684	194/8465	1.68e-06	2.53e-05	1.94e-05	36
hsa0461219	Breast	Precancer	Antigen processing and presentation	19/684	78/8465	9.61e-06	1.12e-04	8.62e-05	19
hsa0516919	Breast	Precancer	Epstein-Barr virus infection	35/684	202/8465	1.15e-05	1.26e-04	9.64e-05	35
hsa0421814	Breast	Precancer	Cellular senescence	29/684	156/8465	1.66e-05	1.69e-04	1.30e-04	29
hsa0414519	Breast	Precancer	Phagosome	27/684	152/8465	7.37e-05	6.85e-04	5.25e-04	27
hsa0541619	Breast	Precancer	Viral myocarditis	14/684	60/8465	2.32e-04	1.98e-03	1.52e-03	14
hsa0516619	Breast	Precancer	Human T-cell leukemia virus 1 infection	33/684	222/8465	4.29e-04	3.31e-03	2.53e-03	33
hsa0516317	Breast	Precancer	Human cytomegalovirus infection	32/684	225/8465	1.13e-03	7.57e-03	5.80e-03	32
hsa0520312	Breast	Precancer	Viral carcinogenesis	27/684	204/8465	7.19e-03	4.06e-02	3.11e-02	27
hsa0516922	Breast	IDC	Epstein-Barr virus infection	45/867	202/8465	3.16e-07	6.05e-06	4.52e-06	45
hsa0461223	Breast	IDC	Antigen processing and presentation	24/867	78/8465	4.61e-07	8.33e-06	6.23e-06	24

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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
HLA-A	CD8A	HLA-A_CD8A	MHC-I	Breast	ADJ
HLA-A	CD8B	HLA-A_CD8B	MHC-I	Breast	ADJ
HLA-A	CD8A	HLA-A_CD8A	MHC-I	Breast	DCIS
HLA-A	CD8B	HLA-A_CD8B	MHC-I	Breast	DCIS
HLA-A	CD8A	HLA-A_CD8A	MHC-I	Breast	Healthy
HLA-A	CD8B	HLA-A_CD8B	MHC-I	Breast	Healthy
HLA-A	CD8A	HLA-A_CD8A	MHC-I	Breast	IDC
HLA-A	CD8B	HLA-A_CD8B	MHC-I	Breast	IDC
HLA-A	CD8A	HLA-A_CD8A	MHC-I	Breast	Precancer
HLA-A	CD8B	HLA-A_CD8B	MHC-I	Breast	Precancer
HLA-A	CD8A	HLA-A_CD8A	MHC-I	Cervix	ADJ
HLA-A	CD8B	HLA-A_CD8B	MHC-I	Cervix	ADJ
HLA-A	CD8A	HLA-A_CD8A	MHC-I	Cervix	CC
HLA-A	CD8B	HLA-A_CD8B	MHC-I	Cervix	CC
HLA-A	CD8A	HLA-A_CD8A	MHC-I	Cervix	Healthy
HLA-A	CD8B	HLA-A_CD8B	MHC-I	Cervix	Healthy
HLA-A	CD8A	HLA-A_CD8A	MHC-I	Cervix	Precancer
HLA-A	CD8B	HLA-A_CD8B	MHC-I	Cervix	Precancer
HLA-A	CD8A	HLA-A_CD8A	MHC-I	CRC	AD
HLA-A	CD8B	HLA-A_CD8B	MHC-I	CRC	AD

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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

HLA-A

SNV

Missense_Mutation

c.640N>C

p.Thr214Pro

p.T214P

P04439,P13746,P16188

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.916)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HLA-A

SNV

Missense_Mutation

rs199474387

c.187N>C

p.Asp63His

p.D63H

P04439,P13746,P16188

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HLA-A

SNV

Missense_Mutation

rs199474481

c.360N>C

p.Gln120His

p.Q120H

P04439,P13746,P16188

protein_coding

deleterious_low_confidence(0)

benign(0.025)

TCGA-Q1-A73P-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HLA-A

SNV

Missense_Mutation

c.296N>C

p.Arg99Pro

p.R99P

P04439,P13746,P16188

protein_coding

deleterious_low_confidence(0.04)

probably_damaging(0.954)

TCGA-UC-A7PI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HLA-A

SNV

Missense_Mutation

novel

c.1016G>A

p.Arg339Lys

p.R339K

P04439,P13746,P16188

protein_coding

tolerated_low_confidence(0.95)

benign(0.019)

TCGA-VS-A9UD-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

HLA-A

insertion

Frame_Shift_Ins

novel

c.620_621insACCC

p.Asp207GlufsTer15

p.D207Efs*15

P04439,P13746,P16188

protein_coding

TCGA-EK-A2PK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HLA-A

insertion

Frame_Shift_Ins

novel

c.620_621insC

p.Lys210GlnfsTer11

p.K210Qfs*11

P04439,P13746,P16188

protein_coding

TCGA-EK-A2PL-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

HLA-A

SNV

Missense_Mutation

novel

c.776C>A

p.Pro259His

p.P259H

P04439,P13746,P16188

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-5M-AAT6-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Unknown

HLA-A

SNV

Missense_Mutation

c.373N>C

p.Cys125Arg

p.C125R

P04439,P13746,P16188

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-A6-6781-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

oxaliplatin

HLA-A

SNV

Missense_Mutation

rs758168864

c.547T>C

p.Tyr183His

p.Y183H

P04439,P13746,P16188

protein_coding

deleterious_low_confidence(0.02)

probably_damaging(0.956)

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
3105	HLA-A	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		peginterferon alfa-2b		23360626
3105	HLA-A	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		zonisamide	ZONISAMIDE	24236482
3105	HLA-A	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		terbinafine	TERBINAFINE
3105	HLA-A	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		peginterferon alfa-2a		23360626
3105	HLA-A	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		ticlopidine	TICLOPIDINE	17339877
3105	HLA-A	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		Carbamazepine	CARBAMAZEPINE
3105	HLA-A	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		ribavirin	RIBAVIRIN	23360626
3105	HLA-A	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		vancomycin	VANCOMYCIN	32439433
3105	HLA-A	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		levetiracetam	LEVETIRACETAM	30020991
3105	HLA-A	CELL SURFACE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME		sertraline	SERTRALINE

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