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: CIT

Gene summary for CIT

Gene summary.

Gene information	Species	Human
	Gene symbol	CIT
	Gene ID	11113
	Gene name	citron rho-interacting serine/threonine kinase
	Gene Alias	CITK
	Cytomap	12q24.23
	Gene Type	protein-coding
	GO ID	GO:0000278
	UniProtAcc	O14578

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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
11113	CIT	TD9	Human	Lung	IAC	1.02e-02	5.71e-01	0.088
11113	CIT	RNA-P6T1-P6T1-1	Human	Lung	MIAC	6.67e-04	9.05e-01	-0.0238

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma

∗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:00018925	Liver	Cirrhotic	embryonic placenta development	34/4634	82/18723	6.36e-04	4.85e-03	34
GO:004887212	Liver	Cirrhotic	homeostasis of number of cells	89/4634	272/18723	1.76e-03	1.12e-02	89
GO:00614585	Liver	Cirrhotic	reproductive system development	132/4634	427/18723	2.07e-03	1.28e-02	132
GO:00486085	Liver	Cirrhotic	reproductive structure development	131/4634	424/18723	2.19e-03	1.34e-02	131
GO:00025735	Liver	Cirrhotic	myeloid leukocyte differentiation	70/4634	208/18723	2.34e-03	1.42e-02	70
GO:0043627	Liver	Cirrhotic	response to estrogen	30/4634	75/18723	2.52e-03	1.51e-02	30
GO:190384411	Liver	Cirrhotic	regulation of cellular response to transforming growth factor beta stimulus	47/4634	131/18723	2.87e-03	1.65e-02	47
GO:000717811	Liver	Cirrhotic	transmembrane receptor protein serine/threonine kinase signaling pathway	111/4634	355/18723	2.98e-03	1.70e-02	111
GO:00170152	Liver	Cirrhotic	regulation of transforming growth factor beta receptor signaling pathway	46/4634	128/18723	3.04e-03	1.72e-02	46
GO:0007565	Liver	Cirrhotic	female pregnancy	65/4634	193/18723	3.21e-03	1.80e-02	65
GO:00305112	Liver	Cirrhotic	positive regulation of transforming growth factor beta receptor signaling pathway	15/4634	32/18723	5.36e-03	2.73e-02	15
GO:19038462	Liver	Cirrhotic	positive regulation of cellular response to transforming growth factor beta stimulus	15/4634	32/18723	5.36e-03	2.73e-02	15
GO:00018932	Liver	Cirrhotic	maternal placenta development	16/4634	35/18723	5.53e-03	2.80e-02	16
GO:0001825	Liver	Cirrhotic	blastocyst formation	17/4634	38/18723	5.62e-03	2.84e-02	17
GO:00457874	Liver	Cirrhotic	positive regulation of cell cycle	97/4634	313/18723	6.88e-03	3.38e-02	97
GO:0044706	Liver	Cirrhotic	multi-multicellular organism process	70/4634	220/18723	1.03e-02	4.61e-02	70
GO:0060135	Liver	Cirrhotic	maternal process involved in female pregnancy	24/4634	62/18723	1.03e-02	4.61e-02	24
GO:004886311	Liver	Cirrhotic	stem cell differentiation	66/4634	206/18723	1.06e-02	4.68e-02	66
GO:000188922	Liver	HCC	liver development	108/7958	147/18723	2.16e-14	1.41e-12	108
GO:006100822	Liver	HCC	hepaticobiliary system development	109/7958	150/18723	5.72e-14	3.42e-12	109

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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

CIT

SNV

Missense_Mutation

rs779515686

c.4130N>T

p.Pro1377Leu

p.P1377L

O14578

protein_coding

deleterious(0)

benign(0.248)

TCGA-A2-A0EW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

CIT

SNV

Missense_Mutation

c.5132C>T

p.Ser1711Phe

p.S1711F

O14578

protein_coding

deleterious(0)

probably_damaging(0.972)

TCGA-A2-A0SV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate therapy

zometa

CIT

SNV

Missense_Mutation

novel

c.2482N>A

p.Glu828Lys

p.E828K

O14578

protein_coding

deleterious(0.04)

possibly_damaging(0.628)

TCGA-A2-A25C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

CIT

SNV

Missense_Mutation

c.3097G>T

p.Val1033Leu

p.V1033L

O14578

protein_coding

tolerated(0.08)

probably_damaging(0.978)

TCGA-A8-A076-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

CIT

SNV

Missense_Mutation

rs747447396

c.2839C>T

p.Arg947Cys

p.R947C

O14578

protein_coding

deleterious(0.02)

possibly_damaging(0.446)

TCGA-A8-A09X-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CIT

SNV

Missense_Mutation

rs747447396

c.2839N>T

p.Arg947Cys

p.R947C

O14578

protein_coding

deleterious(0.02)

possibly_damaging(0.446)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CIT

SNV

Missense_Mutation

c.242N>T

p.Ser81Phe

p.S81F

O14578

protein_coding

deleterious(0.02)

benign(0.17)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CIT

SNV

Missense_Mutation

novel

c.637N>T

p.His213Tyr

p.H213Y

O14578

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

CIT

SNV

Missense_Mutation

rs368981957

c.5590N>A

p.Asp1864Asn

p.D1864N

O14578

protein_coding

deleterious(0)

probably_damaging(0.964)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CIT

SNV

Missense_Mutation

novel

c.1771N>A

p.Glu591Lys

p.E591K

O14578

protein_coding

tolerated(0.31)

benign(0.019)

TCGA-AN-A046-01

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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