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: TNRC6B

Gene summary for TNRC6B

Gene summary.

Gene information	Species	Human
	Gene symbol	TNRC6B
	Gene ID	23112
	Gene name	trinucleotide repeat containing adaptor 6B
	Gene Alias	GDSBA
	Cytomap	22q13.1
	Gene Type	protein-coding
	GO ID	GO:0000288
	UniProtAcc	A0A024R1N5

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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
23112	TNRC6B	CA_HPV_1	Human	Cervix	CC	3.26e-03	-5.85e-03	0.0264
23112	TNRC6B	CA_HPV_3	Human	Cervix	CC	2.78e-04	6.75e-02	0.0414
23112	TNRC6B	CCI_2	Human	Cervix	CC	8.12e-12	1.04e+00	0.5249
23112	TNRC6B	CCI_3	Human	Cervix	CC	4.62e-12	1.05e+00	0.516
23112	TNRC6B	CCII_1	Human	Cervix	CC	1.52e-02	-3.79e-01	0.3249
23112	TNRC6B	Tumor	Human	Cervix	CC	1.80e-02	-2.77e-01	0.1241
23112	TNRC6B	T3	Human	Cervix	CC	5.99e-06	-2.68e-01	0.1389
23112	TNRC6B	HTA11_3410_2000001011	Human	Colorectum	AD	1.34e-19	-4.89e-01	0.0155
23112	TNRC6B	HTA11_347_2000001011	Human	Colorectum	AD	2.54e-12	6.08e-01	-0.1954
23112	TNRC6B	HTA11_8622_2000001021	Human	Colorectum	SER	4.89e-04	-3.80e-01	0.0528
23112	TNRC6B	HTA11_6818_2000001021	Human	Colorectum	AD	1.23e-04	-4.45e-01	0.0588
23112	TNRC6B	HTA11_99999970781_79442	Human	Colorectum	MSS	1.22e-05	-3.19e-01	0.294
23112	TNRC6B	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.11e-02	6.74e-01	0.3487
23112	TNRC6B	HTA11_99999974143_84620	Human	Colorectum	MSS	1.07e-18	-5.32e-01	0.3005
23112	TNRC6B	F007	Human	Colorectum	FAP	2.69e-02	-1.48e-01	0.1176
23112	TNRC6B	A001-C-207	Human	Colorectum	FAP	1.09e-02	-1.64e-01	0.1278
23112	TNRC6B	A015-C-203	Human	Colorectum	FAP	8.03e-42	-5.32e-01	-0.1294
23112	TNRC6B	A015-C-204	Human	Colorectum	FAP	1.28e-05	-3.10e-01	-0.0228
23112	TNRC6B	A014-C-040	Human	Colorectum	FAP	1.81e-05	-5.12e-01	-0.1184
23112	TNRC6B	A002-C-201	Human	Colorectum	FAP	6.04e-13	-3.17e-01	0.0324

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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
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
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:000989610	Cervix	CC	positive regulation of catabolic process	109/2311	492/18723	5.26e-10	6.99e-08	109
GO:003133110	Cervix	CC	positive regulation of cellular catabolic process	91/2311	427/18723	9.64e-08	5.25e-06	91
GO:00064029	Cervix	CC	mRNA catabolic process	56/2311	232/18723	4.81e-07	1.83e-05	56
GO:19001517	Cervix	CC	regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	11/2311	18/18723	1.37e-06	4.55e-05	11
GO:19033119	Cervix	CC	regulation of mRNA metabolic process	64/2311	288/18723	1.71e-06	5.64e-05	64
GO:00064019	Cervix	CC	RNA catabolic process	62/2311	278/18723	2.18e-06	6.56e-05	62
GO:00002896	Cervix	CC	nuclear-transcribed mRNA poly(A) tail shortening	13/2311	29/18723	1.48e-05	2.93e-04	13
GO:00602119	Cervix	CC	regulation of nuclear-transcribed mRNA poly(A) tail shortening	9/2311	15/18723	1.63e-05	3.17e-04	9
GO:19001536	Cervix	CC	positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	9/2311	15/18723	1.63e-05	3.17e-04	9
GO:000641710	Cervix	CC	regulation of translation	89/2311	468/18723	1.86e-05	3.46e-04	89
GO:00009567	Cervix	CC	nuclear-transcribed mRNA catabolic process	30/2311	112/18723	2.60e-05	4.37e-04	30
GO:00602139	Cervix	CC	positive regulation of nuclear-transcribed mRNA poly(A) tail shortening	8/2311	13/18723	3.85e-05	6.05e-04	8
GO:00002886	Cervix	CC	nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	18/2311	56/18723	8.42e-05	1.13e-03	18
GO:00610139	Cervix	CC	regulation of mRNA catabolic process	38/2311	166/18723	1.07e-04	1.36e-03	38
GO:19033136	Cervix	CC	positive regulation of mRNA metabolic process	29/2311	118/18723	1.86e-04	2.18e-03	29
GO:00467008	Cervix	CC	heterocycle catabolic process	80/2311	445/18723	3.23e-04	3.42e-03	80
GO:00346559	Cervix	CC	nucleobase-containing compound catabolic process	74/2311	407/18723	3.77e-04	3.88e-03	74
GO:00434889	Cervix	CC	regulation of mRNA stability	35/2311	158/18723	3.80e-04	3.89e-03	35
GO:00611576	Cervix	CC	mRNA destabilization	22/2311	84/18723	4.18e-04	4.23e-03	22
GO:00610146	Cervix	CC	positive regulation of mRNA catabolic process	22/2311	87/18723	7.03e-04	6.40e-03	22

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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

TNRC6B

SNV

Missense_Mutation

c.4778G>T

p.Arg1593Met

p.R1593M

Q9UPQ9

protein_coding

deleterious(0)

probably_damaging(0.987)

TCGA-A2-A04P-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxol

TNRC6B

SNV

Missense_Mutation

c.872N>T

p.Asp291Val

p.D291V

Q9UPQ9

protein_coding

deleterious(0.01)

possibly_damaging(0.522)

TCGA-A2-A04U-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TNRC6B

SNV

Missense_Mutation

c.1277N>T

p.Gly426Val

p.G426V

Q9UPQ9

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-A2-A0YC-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

TNRC6B

SNV

Missense_Mutation

c.4130N>T

p.Ser1377Phe

p.S1377F

Q9UPQ9

protein_coding

tolerated(0.48)

probably_damaging(0.988)

TCGA-A7-A26H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

TNRC6B

SNV

Missense_Mutation

novel

c.4237N>A

p.Glu1413Lys

p.E1413K

Q9UPQ9

protein_coding

deleterious(0)

benign(0.036)

TCGA-A8-A096-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TNRC6B

SNV

Missense_Mutation

rs772135186

c.1769N>A

p.Arg590His

p.R590H

Q9UPQ9

protein_coding

deleterious(0.05)

probably_damaging(0.984)

TCGA-AN-A0XU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TNRC6B

SNV

Missense_Mutation

rs267606255

c.79N>A

p.Glu27Lys

p.E27K

Q9UPQ9

protein_coding

tolerated(0.14)

benign(0.015)

TCGA-B6-A0I5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TNRC6B

SNV

Missense_Mutation

rs267606255

c.79N>A

p.Glu27Lys

p.E27K

Q9UPQ9

protein_coding

tolerated(0.14)

benign(0.015)

TCGA-B6-A1KI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TNRC6B

SNV

Missense_Mutation

c.769N>A

p.Gly257Arg

p.G257R

Q9UPQ9

protein_coding

deleterious(0.03)

probably_damaging(0.998)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

TNRC6B

SNV

Missense_Mutation

rs778520882

c.5N>A

p.Arg2Lys

p.R2K

Q9UPQ9

protein_coding

tolerated_low_confidence(0.08)

benign(0.267)

TCGA-C8-A8HQ-01

Breast

breast invasive 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

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