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: TRPC4AP

Gene summary for TRPC4AP

Gene summary.

Gene information	Species	Human
	Gene symbol	TRPC4AP
	Gene ID	26133
	Gene name	transient receptor potential cation channel subfamily C member 4 associated protein
	Gene Alias	C20orf188
	Cytomap	20q11.22
	Gene Type	protein-coding
	GO ID	GO:0001942
	UniProtAcc	Q8TEL6

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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
26133	TRPC4AP	CCI_1	Human	Cervix	CC	3.64e-03	5.37e-01	0.528
26133	TRPC4AP	CCI_2	Human	Cervix	CC	1.47e-07	7.72e-01	0.5249
26133	TRPC4AP	CCI_3	Human	Cervix	CC	3.98e-03	3.84e-01	0.516
26133	TRPC4AP	LZE4T	Human	Esophagus	ESCC	7.56e-22	3.94e-01	0.0811
26133	TRPC4AP	LZE5T	Human	Esophagus	ESCC	1.18e-02	3.52e-01	0.0514
26133	TRPC4AP	LZE7T	Human	Esophagus	ESCC	5.64e-07	5.03e-01	0.0667
26133	TRPC4AP	LZE20T	Human	Esophagus	ESCC	3.98e-08	2.13e-01	0.0662
26133	TRPC4AP	LZE21D1	Human	Esophagus	HGIN	1.35e-02	2.08e-01	0.0632
26133	TRPC4AP	LZE22D1	Human	Esophagus	HGIN	1.51e-03	9.33e-02	0.0595
26133	TRPC4AP	LZE22T	Human	Esophagus	ESCC	2.02e-04	2.74e-01	0.068
26133	TRPC4AP	LZE24D1	Human	Esophagus	HGIN	2.15e-02	3.97e-01	0.054
26133	TRPC4AP	LZE24T	Human	Esophagus	ESCC	4.28e-23	7.84e-01	0.0596
26133	TRPC4AP	LZE21T	Human	Esophagus	ESCC	1.10e-05	2.11e-01	0.0655
26133	TRPC4AP	P1T-E	Human	Esophagus	ESCC	1.49e-10	6.09e-01	0.0875
26133	TRPC4AP	P2T-E	Human	Esophagus	ESCC	1.01e-32	4.88e-01	0.1177
26133	TRPC4AP	P4T-E	Human	Esophagus	ESCC	1.28e-21	4.30e-01	0.1323
26133	TRPC4AP	P5T-E	Human	Esophagus	ESCC	1.37e-16	2.54e-01	0.1327
26133	TRPC4AP	P8T-E	Human	Esophagus	ESCC	8.38e-40	6.45e-01	0.0889
26133	TRPC4AP	P9T-E	Human	Esophagus	ESCC	4.65e-15	3.41e-01	0.1131
26133	TRPC4AP	P10T-E	Human	Esophagus	ESCC	3.35e-32	5.78e-01	0.116

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:00085446	Cervix	CC	epidermis development	83/2311	324/18723	3.91e-11	8.54e-09	83
GO:00435884	Cervix	CC	skin development	71/2311	263/18723	8.04e-11	1.46e-08	71
GO:001049810	Cervix	CC	proteasomal protein catabolic process	111/2311	490/18723	8.98e-11	1.58e-08	111
GO:004316110	Cervix	CC	proteasome-mediated ubiquitin-dependent protein catabolic process	91/2311	412/18723	1.65e-08	1.25e-06	91
GO:001049826	Esophagus	HGIN	proteasomal protein catabolic process	139/2587	490/18723	1.20e-17	3.41e-15	139
GO:004316126	Esophagus	HGIN	proteasome-mediated ubiquitin-dependent protein catabolic process	114/2587	412/18723	7.00e-14	1.20e-11	114
GO:0010498111	Esophagus	ESCC	proteasomal protein catabolic process	369/8552	490/18723	1.13e-41	1.80e-38	369
GO:0043161111	Esophagus	ESCC	proteasome-mediated ubiquitin-dependent protein catabolic process	312/8552	412/18723	3.53e-36	4.48e-33	312
GO:00435888	Esophagus	ESCC	skin development	163/8552	263/18723	6.48e-08	1.14e-06	163
GO:000854410	Esophagus	ESCC	epidermis development	193/8552	324/18723	2.87e-07	4.19e-06	193
GO:00224043	Esophagus	ESCC	molting cycle process	53/8552	84/18723	9.62e-04	4.88e-03	53
GO:00224053	Esophagus	ESCC	hair cycle process	53/8552	84/18723	9.62e-04	4.88e-03	53
GO:0001942	Esophagus	ESCC	hair follicle development	51/8552	81/18723	1.27e-03	6.14e-03	51
GO:0098773	Esophagus	ESCC	skin epidermis development	53/8552	85/18723	1.43e-03	6.77e-03	53
GO:00423033	Esophagus	ESCC	molting cycle	64/8552	107/18723	2.24e-03	9.85e-03	64
GO:00426333	Esophagus	ESCC	hair cycle	64/8552	107/18723	2.24e-03	9.85e-03	64
GO:00488201	Esophagus	ESCC	hair follicle maturation	11/8552	13/18723	4.76e-03	1.85e-02	11
GO:00431617	Liver	NAFLD	proteasome-mediated ubiquitin-dependent protein catabolic process	91/1882	412/18723	3.00e-13	1.75e-10	91
GO:00104987	Liver	NAFLD	proteasomal protein catabolic process	101/1882	490/18723	1.35e-12	6.09e-10	101
GO:001049822	Liver	HCC	proteasomal protein catabolic process	351/7958	490/18723	6.92e-40	1.46e-36	351

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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

TRPC4AP

SNV

Missense_Mutation

novel

c.2123N>C

p.Tyr708Ser

p.Y708S

Q8TEL6

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

TRPC4AP

SNV

Missense_Mutation

novel

c.1885N>A

p.Arg629Ser

p.R629S

Q8TEL6

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

TRPC4AP

SNV

Missense_Mutation

c.1057N>G

p.Ile353Val

p.I353V

Q8TEL6

protein_coding

tolerated(1)

benign(0)

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

TRPC4AP

SNV

Missense_Mutation

c.1360N>A

p.Leu454Met

p.L454M

Q8TEL6

protein_coding

deleterious(0.01)

probably_damaging(0.93)

TCGA-BH-A0C0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

TRPC4AP

SNV

Missense_Mutation

rs11552601

c.2140N>T

p.Arg714Trp

p.R714W

Q8TEL6

protein_coding

deleterious(0)

possibly_damaging(0.663)

TCGA-C8-A3M7-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

TRPC4AP

SNV

Missense_Mutation

novel

c.469N>G

p.Lys157Glu

p.K157E

Q8TEL6

protein_coding

tolerated(0.26)

benign(0.037)

TCGA-E9-A3HO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

TRPC4AP

deletion

In_Frame_Del

c.1491_1493delNNN

p.Glu497_Ala498delinsAsp

p.E497_A498delinsD

Q8TEL6

protein_coding

TCGA-BH-A0GY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyotxan

TRPC4AP

deletion

Frame_Shift_Del

novel

c.1376delN

p.Leu459Ter

p.L459*

Q8TEL6

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

TRPC4AP

SNV

Missense_Mutation

c.1724C>T

p.Ser575Leu

p.S575L

Q8TEL6

protein_coding

tolerated(0.1)

probably_damaging(0.977)

TCGA-C5-A1MJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TRPC4AP

SNV

Missense_Mutation

c.1226N>A

p.Arg409Lys

p.R409K

Q8TEL6

protein_coding

tolerated(0.77)

benign(0.001)

TCGA-EK-A2RA-01

Cervix

cervical & endocervical cancer

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

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