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: TIA1

Gene summary for TIA1

Gene summary.

Gene information	Species	Human
	Gene symbol	TIA1
	Gene ID	7072
	Gene name	TIA1 cytotoxic granule associated RNA binding protein
	Gene Alias	ALS26
	Cytomap	2p13.3
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	P31483

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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
7072	TIA1	P44T-E	Human	Esophagus	ESCC	4.05e-18	2.64e-01	0.1096
7072	TIA1	P47T-E	Human	Esophagus	ESCC	8.60e-17	3.27e-01	0.1067
7072	TIA1	P48T-E	Human	Esophagus	ESCC	8.59e-14	3.77e-01	0.0959
7072	TIA1	P49T-E	Human	Esophagus	ESCC	4.03e-11	1.19e+00	0.1768
7072	TIA1	P52T-E	Human	Esophagus	ESCC	7.59e-17	3.92e-01	0.1555
7072	TIA1	P54T-E	Human	Esophagus	ESCC	1.19e-17	4.38e-01	0.0975
7072	TIA1	P56T-E	Human	Esophagus	ESCC	1.32e-09	1.36e+00	0.1613
7072	TIA1	P57T-E	Human	Esophagus	ESCC	1.59e-21	5.19e-01	0.0926
7072	TIA1	P61T-E	Human	Esophagus	ESCC	6.17e-22	5.63e-01	0.099
7072	TIA1	P62T-E	Human	Esophagus	ESCC	4.05e-47	8.23e-01	0.1302
7072	TIA1	P65T-E	Human	Esophagus	ESCC	3.45e-19	3.29e-01	0.0978
7072	TIA1	P74T-E	Human	Esophagus	ESCC	1.89e-15	5.39e-01	0.1479
7072	TIA1	P75T-E	Human	Esophagus	ESCC	4.74e-27	5.99e-01	0.1125
7072	TIA1	P76T-E	Human	Esophagus	ESCC	1.97e-22	4.13e-01	0.1207
7072	TIA1	P79T-E	Human	Esophagus	ESCC	6.20e-41	8.32e-01	0.1154
7072	TIA1	P80T-E	Human	Esophagus	ESCC	6.10e-27	7.67e-01	0.155
7072	TIA1	P82T-E	Human	Esophagus	ESCC	7.28e-10	5.57e-01	0.1072
7072	TIA1	P83T-E	Human	Esophagus	ESCC	4.82e-16	5.06e-01	0.1738
7072	TIA1	P84T-E	Human	Esophagus	ESCC	1.31e-07	7.29e-01	0.0933
7072	TIA1	P89T-E	Human	Esophagus	ESCC	1.17e-09	4.16e-01	0.1752

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0008380	Colorectum	AD	RNA splicing	169/3918	434/18723	3.59e-18	2.04e-15	169
GO:0000377	Colorectum	AD	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	130/3918	320/18723	5.88e-16	2.16e-13	130
GO:0000398	Colorectum	AD	mRNA splicing, via spliceosome	130/3918	320/18723	5.88e-16	2.16e-13	130
GO:0000375	Colorectum	AD	RNA splicing, via transesterification reactions	131/3918	324/18723	7.11e-16	2.22e-13	131
GO:1903311	Colorectum	AD	regulation of mRNA metabolic process	117/3918	288/18723	1.69e-14	4.23e-12	117
GO:0043484	Colorectum	AD	regulation of RNA splicing	70/3918	148/18723	6.47e-13	1.16e-10	70
GO:0048024	Colorectum	AD	regulation of mRNA splicing, via spliceosome	50/3918	101/18723	1.62e-10	1.56e-08	50
GO:0050684	Colorectum	AD	regulation of mRNA processing	61/3918	137/18723	4.23e-10	3.58e-08	61
GO:0006417	Colorectum	AD	regulation of translation	141/3918	468/18723	1.32e-06	4.22e-05	141
GO:00083801	Colorectum	SER	RNA splicing	123/2897	434/18723	3.84e-12	8.41e-10	123
GO:00003751	Colorectum	SER	RNA splicing, via transesterification reactions	90/2897	324/18723	8.68e-09	7.50e-07	90
GO:00003771	Colorectum	SER	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	89/2897	320/18723	9.82e-09	8.14e-07	89
GO:00003981	Colorectum	SER	mRNA splicing, via spliceosome	89/2897	320/18723	9.82e-09	8.14e-07	89
GO:00434841	Colorectum	SER	regulation of RNA splicing	49/2897	148/18723	7.02e-08	4.49e-06	49
GO:19033111	Colorectum	SER	regulation of mRNA metabolic process	78/2897	288/18723	2.61e-07	1.43e-05	78
GO:00480241	Colorectum	SER	regulation of mRNA splicing, via spliceosome	35/2897	101/18723	1.52e-06	6.85e-05	35
GO:00506841	Colorectum	SER	regulation of mRNA processing	42/2897	137/18723	5.57e-06	2.01e-04	42
GO:00064171	Colorectum	SER	regulation of translation	100/2897	468/18723	3.76e-04	5.74e-03	100
GO:00083802	Colorectum	MSS	RNA splicing	159/3467	434/18723	1.75e-19	1.22e-16	159
GO:19033112	Colorectum	MSS	regulation of mRNA metabolic process	115/3467	288/18723	1.23e-17	6.41e-15	115

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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

TIA1

SNV

Missense_Mutation

novel

c.920G>T

p.Gly307Val

p.G307V

P31483

protein_coding

deleterious(0.01)

possibly_damaging(0.548)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

TIA1

SNV

Missense_Mutation

c.319N>T

p.His107Tyr

p.H107Y

P31483

protein_coding

deleterious(0)

probably_damaging(0.986)

TCGA-A7-A0DA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TIA1

SNV

Missense_Mutation

c.865N>C

p.Asp289His

p.D289H

P31483

protein_coding

deleterious(0)

probably_damaging(0.984)

TCGA-AR-A24Q-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

TIA1

SNV

Missense_Mutation

c.1059G>C

p.Trp353Cys

p.W353C

P31483

protein_coding

deleterious(0.03)

benign(0.006)

TCGA-EW-A1J5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TIA1

insertion

Nonsense_Mutation

novel

c.981_982insATTTAAAACATGTAATATAAAGATGTTAAAAAAAAAAAC

p.Trp327_Gln328insIleTerAsnMetTerTyrLysAspValLysLysLysAsn

p.W327_Q328insI*NM*YKDVKKKN

P31483

protein_coding

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TIA1

insertion

Frame_Shift_Ins

novel

c.257_258insACAATTA

p.Ser86ArgfsTer11

p.S86Rfs*11

P31483

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TIA1

SNV

Missense_Mutation

novel

c.1107N>A

p.Ser369Arg

p.S369R

P31483

protein_coding

deleterious(0.02)

benign(0.051)

TCGA-C5-A8ZZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unspecific

Cisplatin

TIA1

SNV

Missense_Mutation

novel

c.29N>G

p.Tyr10Cys

p.Y10C

P31483

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AA-A022-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

TIA1

SNV

Missense_Mutation

rs756853891

c.562G>A

p.Ala188Thr

p.A188T

P31483

protein_coding

tolerated(0.29)

benign(0.015)

TCGA-AD-A5EJ-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

TIA1

SNV

Missense_Mutation

c.763N>T

p.Arg255Trp

p.R255W

P31483

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AG-A002-01

Colorectum

rectum 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

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