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: TCIRG1

Gene summary for TCIRG1

Gene summary.

Gene information	Species	Human
	Gene symbol	TCIRG1
	Gene ID	10312
	Gene name	T cell immune regulator 1, ATPase H+ transporting V0 subunit a3
	Gene Alias	ATP6N1C
	Cytomap	11q13.2
	Gene Type	protein-coding
	GO ID	GO:0000045
	UniProtAcc	A0A024R5E5

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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
10312	TCIRG1	LZE4T	Human	Esophagus	ESCC	8.50e-06	1.25e-01	0.0811
10312	TCIRG1	LZE7T	Human	Esophagus	ESCC	1.31e-08	2.54e-01	0.0667
10312	TCIRG1	LZE8T	Human	Esophagus	ESCC	1.04e-04	2.60e-01	0.067
10312	TCIRG1	LZE20T	Human	Esophagus	ESCC	9.69e-20	6.87e-01	0.0662
10312	TCIRG1	LZE22D1	Human	Esophagus	HGIN	2.85e-05	2.09e-01	0.0595
10312	TCIRG1	LZE22T	Human	Esophagus	ESCC	5.15e-03	3.42e-01	0.068
10312	TCIRG1	LZE24T	Human	Esophagus	ESCC	1.44e-06	2.64e-01	0.0596
10312	TCIRG1	LZE6T	Human	Esophagus	ESCC	2.22e-04	2.49e-01	0.0845
10312	TCIRG1	P1T-E	Human	Esophagus	ESCC	1.14e-12	5.38e-01	0.0875
10312	TCIRG1	P2T-E	Human	Esophagus	ESCC	9.01e-14	2.85e-01	0.1177
10312	TCIRG1	P4T-E	Human	Esophagus	ESCC	1.09e-14	3.22e-01	0.1323
10312	TCIRG1	P5T-E	Human	Esophagus	ESCC	2.52e-28	5.03e-01	0.1327
10312	TCIRG1	P8T-E	Human	Esophagus	ESCC	1.09e-47	8.63e-01	0.0889
10312	TCIRG1	P9T-E	Human	Esophagus	ESCC	3.47e-17	1.81e-01	0.1131
10312	TCIRG1	P11T-E	Human	Esophagus	ESCC	5.33e-21	6.69e-01	0.1426
10312	TCIRG1	P12T-E	Human	Esophagus	ESCC	2.22e-13	2.14e-01	0.1122
10312	TCIRG1	P15T-E	Human	Esophagus	ESCC	2.69e-17	4.43e-01	0.1149
10312	TCIRG1	P16T-E	Human	Esophagus	ESCC	4.44e-10	1.40e-01	0.1153
10312	TCIRG1	P17T-E	Human	Esophagus	ESCC	3.30e-10	3.95e-01	0.1278
10312	TCIRG1	P19T-E	Human	Esophagus	ESCC	6.22e-08	5.51e-01	0.1662

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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
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:001623616	Esophagus	HGIN	macroautophagy	77/2587	291/18723	7.15e-09	4.61e-07	77
GO:005165616	Esophagus	HGIN	establishment of organelle localization	90/2587	390/18723	4.27e-07	1.94e-05	90
GO:190260017	Esophagus	HGIN	proton transmembrane transport	43/2587	157/18723	5.51e-06	1.75e-04	43
GO:003009927	Esophagus	HGIN	myeloid cell differentiation	83/2587	381/18723	1.26e-05	3.52e-04	83
GO:00070336	Esophagus	HGIN	vacuole organization	44/2587	180/18723	8.97e-05	1.96e-03	44
GO:19050375	Esophagus	HGIN	autophagosome organization	28/2587	103/18723	2.58e-04	4.53e-03	28
GO:000164917	Esophagus	HGIN	osteoblast differentiation	50/2587	229/18723	5.88e-04	8.30e-03	50
GO:00000455	Esophagus	HGIN	autophagosome assembly	26/2587	99/18723	7.45e-04	9.90e-03	26
GO:00101557	Esophagus	HGIN	regulation of proton transport	10/2587	24/18723	7.66e-04	1.00e-02	10
GO:000257316	Esophagus	HGIN	myeloid leukocyte differentiation	45/2587	208/18723	1.31e-03	1.56e-02	45
GO:004887227	Esophagus	HGIN	homeostasis of number of cells	54/2587	272/18723	3.50e-03	3.23e-02	54
GO:005165010	Esophagus	HGIN	establishment of vesicle localization	35/2587	161/18723	3.89e-03	3.54e-02	35
GO:000150316	Esophagus	HGIN	ossification	75/2587	408/18723	5.49e-03	4.49e-02	75
GO:005164810	Esophagus	HGIN	vesicle localization	37/2587	177/18723	6.03e-03	4.87e-02	37
GO:001623617	Esophagus	ESCC	macroautophagy	216/8552	291/18723	1.94e-23	4.57e-21	216
GO:005165617	Esophagus	ESCC	establishment of organelle localization	273/8552	390/18723	9.13e-23	1.81e-20	273
GO:000703314	Esophagus	ESCC	vacuole organization	127/8552	180/18723	1.04e-11	3.85e-10	127
GO:005165016	Esophagus	ESCC	establishment of vesicle localization	114/8552	161/18723	8.20e-11	2.53e-09	114
GO:0030099111	Esophagus	ESCC	myeloid cell differentiation	232/8552	381/18723	1.22e-09	2.90e-08	232
GO:000716320	Esophagus	ESCC	establishment or maintenance of cell polarity	143/8552	218/18723	2.05e-09	4.65e-08	143

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0019030	Esophagus	HGIN	Oxidative phosphorylation	68/1383	134/8465	1.73e-20	8.07e-19	6.41e-19	68
hsa041426	Esophagus	HGIN	Lysosome	33/1383	132/8465	6.65e-03	4.37e-02	3.47e-02	33
hsa00190113	Esophagus	HGIN	Oxidative phosphorylation	68/1383	134/8465	1.73e-20	8.07e-19	6.41e-19	68
hsa0414213	Esophagus	HGIN	Lysosome	33/1383	132/8465	6.65e-03	4.37e-02	3.47e-02	33
hsa00190210	Esophagus	ESCC	Oxidative phosphorylation	104/4205	134/8465	2.04e-11	2.98e-10	1.53e-10	104
hsa0414222	Esophagus	ESCC	Lysosome	102/4205	132/8465	5.11e-11	7.13e-10	3.65e-10	102
hsa0516510	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa0512018	Esophagus	ESCC	Epithelial cell signaling in Helicobacter pylori infection	52/4205	70/8465	2.17e-05	1.07e-04	5.47e-05	52
hsa0414530	Esophagus	ESCC	Phagosome	100/4205	152/8465	3.81e-05	1.72e-04	8.82e-05	100
hsa051527	Esophagus	ESCC	Tuberculosis	111/4205	180/8465	7.14e-04	2.32e-03	1.19e-03	111
hsa0532320	Esophagus	ESCC	Rheumatoid arthritis	59/4205	93/8465	4.98e-03	1.27e-02	6.52e-03	59
hsa0511028	Esophagus	ESCC	Vibrio cholerae infection	34/4205	50/8465	6.62e-03	1.62e-02	8.30e-03	34
hsa0019038	Esophagus	ESCC	Oxidative phosphorylation	104/4205	134/8465	2.04e-11	2.98e-10	1.53e-10	104
hsa0414232	Esophagus	ESCC	Lysosome	102/4205	132/8465	5.11e-11	7.13e-10	3.65e-10	102
hsa0516515	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa0512019	Esophagus	ESCC	Epithelial cell signaling in Helicobacter pylori infection	52/4205	70/8465	2.17e-05	1.07e-04	5.47e-05	52
hsa04145114	Esophagus	ESCC	Phagosome	100/4205	152/8465	3.81e-05	1.72e-04	8.82e-05	100
hsa0515212	Esophagus	ESCC	Tuberculosis	111/4205	180/8465	7.14e-04	2.32e-03	1.19e-03	111
hsa05323110	Esophagus	ESCC	Rheumatoid arthritis	59/4205	93/8465	4.98e-03	1.27e-02	6.52e-03	59
hsa05110112	Esophagus	ESCC	Vibrio cholerae infection	34/4205	50/8465	6.62e-03	1.62e-02	8.30e-03	34

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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

TCIRG1

SNV

Missense_Mutation

c.2455A>C

p.Lys819Gln

p.K819Q

Q13488

protein_coding

tolerated(0.06)

probably_damaging(0.991)

TCGA-A2-A0T0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

TCIRG1

SNV

Missense_Mutation

rs199914625

c.1421N>T

p.Ser474Leu

p.S474L

Q13488

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A2-A0YK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

TCIRG1

insertion

Frame_Shift_Ins

novel

c.1664_1665insGATG

p.Phe555LeufsTer116

p.F555Lfs*116

Q13488

protein_coding

TCGA-BH-A0HL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

TCIRG1

insertion

In_Frame_Ins

novel

c.1666_1667insTTCCTGGCCCAGCACACGATGCTT

p.Asn556delinsIleProGlyProAlaHisAspAlaTyr

p.N556delinsIPGPAHDAY

Q13488

protein_coding

TCGA-BH-A0HL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

TCIRG1

SNV

Missense_Mutation

rs763119311

c.1904N>T

p.Thr635Met

p.T635M

Q13488

protein_coding

tolerated(0.1)

benign(0.017)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TCIRG1

SNV

Missense_Mutation

novel

c.417N>T

p.Gln139His

p.Q139H

Q13488

protein_coding

tolerated(0.56)

benign(0.003)

TCGA-VS-A9UZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TCIRG1

SNV

Missense_Mutation

novel

c.2110G>A

p.Glu704Lys

p.E704K

Q13488

protein_coding

tolerated(0.18)

benign(0.142)

TCGA-VS-A9V1-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TCIRG1

SNV

Missense_Mutation

rs752218792

c.124N>A

p.Ala42Thr

p.A42T

Q13488

protein_coding

deleterious(0.02)

benign(0.244)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

TCIRG1

SNV

Missense_Mutation

rs764312517

c.2398N>A

p.Ala800Thr

p.A800T

Q13488

protein_coding

tolerated(0.28)

possibly_damaging(0.811)

TCGA-AD-5900-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

TCIRG1

SNV

Missense_Mutation

rs550481991

c.2050N>A

p.Ala684Thr

p.A684T

Q13488

protein_coding

tolerated(0.41)

benign(0.005)

TCGA-AD-6895-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

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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