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: HEXIM1

Gene summary for HEXIM1

Gene summary.

Gene information	Species	Human
	Gene symbol	HEXIM1
	Gene ID	10614
	Gene name	HEXIM P-TEFb complex subunit 1
	Gene Alias	CLP1
	Cytomap	17q21.31
	Gene Type	protein-coding
	GO ID	GO:0000079
	UniProtAcc	O94992

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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
10614	HEXIM1	CA_HPV_1	Human	Cervix	CC	2.04e-04	-8.05e-02	0.0264
10614	HEXIM1	CCII_1	Human	Cervix	CC	4.23e-05	-3.31e-01	0.3249
10614	HEXIM1	T1	Human	Cervix	CC	6.23e-12	6.55e-01	0.0918
10614	HEXIM1	T2	Human	Cervix	CC	1.99e-02	5.12e-01	0.0709
10614	HEXIM1	LZE4T	Human	Esophagus	ESCC	2.47e-09	3.21e-01	0.0811
10614	HEXIM1	LZE5T	Human	Esophagus	ESCC	5.22e-05	1.24e-01	0.0514
10614	HEXIM1	LZE7T	Human	Esophagus	ESCC	1.87e-08	4.21e-01	0.0667
10614	HEXIM1	LZE8T	Human	Esophagus	ESCC	1.38e-07	1.08e-01	0.067
10614	HEXIM1	LZE22T	Human	Esophagus	ESCC	1.97e-02	5.20e-01	0.068
10614	HEXIM1	LZE24T	Human	Esophagus	ESCC	1.39e-13	3.23e-01	0.0596
10614	HEXIM1	P1T-E	Human	Esophagus	ESCC	1.14e-16	1.20e+00	0.0875
10614	HEXIM1	P2T-E	Human	Esophagus	ESCC	1.94e-14	8.68e-02	0.1177
10614	HEXIM1	P4T-E	Human	Esophagus	ESCC	8.50e-15	3.08e-01	0.1323
10614	HEXIM1	P5T-E	Human	Esophagus	ESCC	6.04e-11	2.96e-01	0.1327
10614	HEXIM1	P8T-E	Human	Esophagus	ESCC	3.07e-15	3.57e-01	0.0889
10614	HEXIM1	P9T-E	Human	Esophagus	ESCC	3.77e-14	9.13e-02	0.1131
10614	HEXIM1	P10T-E	Human	Esophagus	ESCC	1.91e-19	2.25e-01	0.116
10614	HEXIM1	P11T-E	Human	Esophagus	ESCC	8.68e-11	7.18e-01	0.1426
10614	HEXIM1	P12T-E	Human	Esophagus	ESCC	6.67e-33	8.11e-01	0.1122
10614	HEXIM1	P15T-E	Human	Esophagus	ESCC	9.57e-12	3.78e-01	0.1149

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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
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
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:00457864	Oral cavity	OSCC	negative regulation of cell cycle	206/7305	385/18723	4.28e-09	9.55e-08	206
GO:00063547	Oral cavity	OSCC	DNA-templated transcription, elongation	63/7305	91/18723	4.86e-09	1.07e-07	63
GO:00028317	Oral cavity	OSCC	regulation of response to biotic stimulus	177/7305	327/18723	1.73e-08	3.43e-07	177
GO:190179620	Oral cavity	OSCC	regulation of signal transduction by p53 class mediator	62/7305	93/18723	5.99e-08	1.09e-06	62
GO:00063686	Oral cavity	OSCC	transcription elongation from RNA polymerase II promoter	48/7305	69/18723	2.60e-07	4.05e-06	48
GO:00190833	Oral cavity	OSCC	viral transcription	36/7305	50/18723	2.26e-06	2.87e-05	36
GO:00719013	Oral cavity	OSCC	negative regulation of protein serine/threonine kinase activity	72/7305	120/18723	2.53e-06	3.17e-05	72
GO:19040293	Oral cavity	OSCC	regulation of cyclin-dependent protein kinase activity	60/7305	98/18723	6.90e-06	7.56e-05	60
GO:00000793	Oral cavity	OSCC	regulation of cyclin-dependent protein serine/threonine kinase activity	58/7305	94/18723	6.92e-06	7.57e-05	58
GO:00450884	Oral cavity	OSCC	regulation of innate immune response	116/7305	218/18723	1.36e-05	1.37e-04	116
GO:00485259	Oral cavity	OSCC	negative regulation of viral process	56/7305	92/18723	1.77e-05	1.72e-04	56
GO:00327843	Oral cavity	OSCC	regulation of DNA-templated transcription, elongation	36/7305	53/18723	1.89e-05	1.83e-04	36
GO:00342434	Oral cavity	OSCC	regulation of transcription elongation from RNA polymerase II promoter	24/7305	32/18723	3.83e-05	3.37e-04	24
GO:00321037	Oral cavity	OSCC	positive regulation of response to external stimulus	203/7305	427/18723	1.79e-04	1.22e-03	203
GO:00342442	Oral cavity	OSCC	negative regulation of transcription elongation from RNA polymerase II promoter	13/7305	16/18723	7.05e-04	3.89e-03	13
GO:00327852	Oral cavity	OSCC	negative regulation of DNA-templated transcription, elongation	14/7305	18/18723	9.51e-04	4.96e-03	14
GO:00022184	Oral cavity	OSCC	activation of innate immune response	31/7305	52/18723	2.08e-03	9.59e-03	31
GO:19040302	Oral cavity	OSCC	negative regulation of cyclin-dependent protein kinase activity	20/7305	33/18723	9.78e-03	3.45e-02	20
GO:190179820	Oral cavity	OSCC	positive regulation of signal transduction by p53 class mediator	16/7305	25/18723	1.00e-02	3.49e-02	16
GO:00313495	Oral cavity	OSCC	positive regulation of defense response	127/7305	278/18723	1.32e-02	4.39e-02	127

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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

HEXIM1

deletion

Frame_Shift_Del

novel

c.762delG

p.Met255TrpfsTer28

p.M255Wfs*28

O94992

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

HEXIM1

deletion

Frame_Shift_Del

novel

c.709_712delNNNN

p.Ser237MetfsTer45

p.S237Mfs*45

O94992

protein_coding

TCGA-OL-A5RW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

HEXIM1

SNV

Missense_Mutation

c.124G>C

p.Glu42Gln

p.E42Q

O94992

protein_coding

tolerated_low_confidence(0.07)

benign(0.003)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HEXIM1

SNV

Missense_Mutation

c.276G>C

p.Gln92His

p.Q92H

O94992

protein_coding

deleterious_low_confidence(0.05)

benign(0.001)

TCGA-VS-A953-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HEXIM1

SNV

Missense_Mutation

c.856G>A

p.Glu286Lys

p.E286K

O94992

protein_coding

deleterious(0)

possibly_damaging(0.908)

TCGA-CK-4951-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

HEXIM1

deletion

In_Frame_Del

c.966_971delNNNNNN

p.Arg323_Glu324del

p.R323_E324del

O94992

protein_coding

TCGA-A6-5665-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

HEXIM1

SNV

Missense_Mutation

novel

c.630N>T

p.Met210Ile

p.M210I

O94992

protein_coding

tolerated(0.05)

probably_damaging(0.946)

TCGA-A5-A0G1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

HEXIM1

SNV

Missense_Mutation

novel

c.940N>T

p.Arg314Trp

p.R314W

O94992

protein_coding

tolerated(0.06)

possibly_damaging(0.861)

TCGA-A5-A0G1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

HEXIM1

SNV

Missense_Mutation

novel

c.445N>A

p.Gly149Arg

p.G149R

O94992

protein_coding

deleterious(0.02)

probably_damaging(0.995)

TCGA-AP-A0LS-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

HEXIM1

SNV

Missense_Mutation

rs756233346

c.225N>C

p.Gln75His

p.Q75H

O94992

protein_coding

tolerated_low_confidence(0.13)

benign(0.192)

TCGA-BG-A222-01

Endometrium

uterine corpus endometrioid 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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