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: CIRBP

Gene summary for CIRBP

Gene summary.

Gene information	Species	Human
	Gene symbol	CIRBP
	Gene ID	1153
	Gene name	cold inducible RNA binding protein
	Gene Alias	CIRP
	Cytomap	19p13.3
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	Q14011

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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
1153	CIRBP	GSM4909281	Human	Breast	IDC	7.21e-11	-4.09e-01	0.21
1153	CIRBP	GSM4909282	Human	Breast	IDC	2.72e-16	-5.57e-01	-0.0288
1153	CIRBP	GSM4909285	Human	Breast	IDC	4.47e-29	-5.84e-01	0.21
1153	CIRBP	GSM4909286	Human	Breast	IDC	7.23e-10	-1.66e-01	0.1081
1153	CIRBP	GSM4909287	Human	Breast	IDC	6.75e-12	-5.71e-01	0.2057
1153	CIRBP	GSM4909294	Human	Breast	IDC	1.01e-05	-2.60e-01	0.2022
1153	CIRBP	GSM4909296	Human	Breast	IDC	4.71e-07	-2.40e-01	0.1524
1153	CIRBP	GSM4909297	Human	Breast	IDC	1.82e-29	1.34e-01	0.1517
1153	CIRBP	GSM4909298	Human	Breast	IDC	6.74e-61	6.18e-01	0.1551
1153	CIRBP	GSM4909299	Human	Breast	IDC	2.39e-19	4.36e-01	0.035
1153	CIRBP	GSM4909300	Human	Breast	IDC	7.31e-11	4.17e-01	0.0334
1153	CIRBP	GSM4909302	Human	Breast	IDC	8.65e-09	2.71e-01	0.1545
1153	CIRBP	GSM4909305	Human	Breast	IDC	1.15e-31	5.56e-01	0.0436
1153	CIRBP	GSM4909306	Human	Breast	IDC	2.02e-12	3.86e-01	0.1564
1153	CIRBP	GSM4909307	Human	Breast	IDC	5.68e-13	3.71e-01	0.1569
1153	CIRBP	GSM4909308	Human	Breast	IDC	9.44e-16	3.93e-01	0.158
1153	CIRBP	GSM4909309	Human	Breast	IDC	1.07e-03	7.88e-02	0.0483
1153	CIRBP	GSM4909311	Human	Breast	IDC	1.50e-46	-4.76e-02	0.1534
1153	CIRBP	GSM4909312	Human	Breast	IDC	1.70e-09	1.29e-01	0.1552
1153	CIRBP	GSM4909313	Human	Breast	IDC	4.22e-31	4.35e-01	0.0391

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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
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:000037541	Stomach	SIM	RNA splicing, via transesterification reactions	25/708	324/18723	6.24e-04	9.29e-03	25
GO:000641751	Stomach	SIM	regulation of translation	32/708	468/18723	9.56e-04	1.27e-02	32
GO:004802631	Stomach	SIM	positive regulation of mRNA splicing, via spliceosome	5/708	22/18723	1.17e-03	1.49e-02	5
GO:000989551	Stomach	SIM	negative regulation of catabolic process	24/708	320/18723	1.18e-03	1.49e-02	24
GO:003312031	Stomach	SIM	positive regulation of RNA splicing	6/708	37/18723	2.44e-03	2.47e-02	6
GO:004802421	Stomach	SIM	regulation of mRNA splicing, via spliceosome	10/708	101/18723	4.88e-03	4.19e-02	10
GO:004348430	Thyroid	HT	regulation of RNA splicing	46/1272	148/18723	4.82e-19	6.71e-16	46
GO:000838028	Thyroid	HT	RNA splicing	84/1272	434/18723	1.23e-18	1.14e-15	84
GO:000037527	Thyroid	HT	RNA splicing, via transesterification reactions	66/1272	324/18723	4.86e-16	2.08e-13	66
GO:000037727	Thyroid	HT	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	65/1272	320/18723	9.43e-16	3.50e-13	65
GO:000039827	Thyroid	HT	mRNA splicing, via spliceosome	65/1272	320/18723	9.43e-16	3.50e-13	65
GO:004802429	Thyroid	HT	regulation of mRNA splicing, via spliceosome	34/1272	101/18723	1.32e-15	4.57e-13	34
GO:005068426	Thyroid	HT	regulation of mRNA processing	39/1272	137/18723	6.30e-15	1.95e-12	39
GO:000641730	Thyroid	HT	regulation of translation	78/1272	468/18723	1.12e-13	2.83e-11	78
GO:190331127	Thyroid	HT	regulation of mRNA metabolic process	56/1272	288/18723	6.33e-13	1.47e-10	56
GO:003425027	Thyroid	HT	positive regulation of cellular amide metabolic process	35/1272	162/18723	7.30e-10	8.12e-08	35
GO:004572727	Thyroid	HT	positive regulation of translation	31/1272	136/18723	1.71e-09	1.78e-07	31
GO:190331229	Thyroid	HT	negative regulation of mRNA metabolic process	24/1272	92/18723	6.91e-09	6.10e-07	24
GO:000989528	Thyroid	HT	negative regulation of catabolic process	50/1272	320/18723	2.72e-08	2.02e-06	50
GO:000640226	Thyroid	HT	mRNA catabolic process	40/1272	232/18723	4.42e-08	2.89e-06	40

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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

CIRBP

SNV

Missense_Mutation

c.820N>A

p.Val274Met

p.V274M

protein_coding

tolerated_low_confidence(0.09)

benign(0.017)

TCGA-A8-A09I-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

CIRBP

SNV

Missense_Mutation

rs749046630

c.493N>A

p.Asp165Asn

p.D165N

protein_coding

deleterious(0)

possibly_damaging(0.632)

TCGA-A8-A0AD-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

CIRBP

SNV

Missense_Mutation

rs148277498

c.791N>A

p.Arg264His

p.R264H

protein_coding

deleterious_low_confidence(0.03)

benign(0)

TCGA-E2-A14Z-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

CIRBP

SNV

Missense_Mutation

c.758C>G

p.Ser253Cys

p.S253C

protein_coding

tolerated_low_confidence(0.06)

benign(0.146)

TCGA-E2-A1IN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

CIRBP

SNV

Missense_Mutation

c.80C>T

p.Ser27Leu

p.S27L

protein_coding

deleterious(0)

probably_damaging(0.975)

TCGA-C5-A7UH-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

CIRBP

SNV

Missense_Mutation

novel

c.643C>G

p.Gln215Glu

p.Q215E

protein_coding

tolerated_low_confidence(0.06)

benign(0)

TCGA-DS-A0VN-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CIRBP

SNV

Missense_Mutation

c.98N>T

p.Ser33Phe

p.S33F

protein_coding

deleterious(0.04)

probably_damaging(0.986)

TCGA-EA-A3HQ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CIRBP

SNV

Missense_Mutation

c.731N>A

p.Arg244Lys

p.R244K

protein_coding

tolerated_low_confidence(0.06)

benign(0)

TCGA-AA-A01D-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

capecitabine

CIRBP

SNV

Missense_Mutation

rs11555031

c.49N>G

p.Thr17Ala

p.T17A

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-AA-A02R-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

CIRBP

SNV

Missense_Mutation

c.5N>T

p.Ala2Val

p.A2V

protein_coding

deleterious(0)

possibly_damaging(0.526)

TCGA-AG-A02N-01

Colorectum

rectum adenocarcinoma

Male

>=65

I/II

Chemotherapy

folinic

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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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