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: UQCRHL

Gene summary for UQCRHL

Gene summary.

Gene information	Species	Human
	Gene symbol	UQCRHL
	Gene ID	440567
	Gene name	ubiquinol-cytochrome c reductase hinge protein like
	Gene Alias	hCG25371
	Cytomap	1p36.21
	Gene Type	protein-coding
	GO ID	GO:0006091
	UniProtAcc	A0A096LP55

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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
440567	UQCRHL	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	5.36e-15	5.88e-01	-0.1869
440567	UQCRHL	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	4.10e-09	5.00e-01	-0.1875
440567	UQCRHL	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	1.02e-12	5.14e-01	-0.1883
440567	UQCRHL	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	4.11e-06	3.10e-01	-0.1917
440567	UQCRHL	P1T-E	Human	Esophagus	ESCC	9.42e-08	3.65e-01	0.0875
440567	UQCRHL	P2T-E	Human	Esophagus	ESCC	3.94e-03	1.15e-01	0.1177
440567	UQCRHL	P4T-E	Human	Esophagus	ESCC	4.69e-05	2.38e-01	0.1323
440567	UQCRHL	P5T-E	Human	Esophagus	ESCC	1.09e-15	3.12e-01	0.1327
440567	UQCRHL	P8T-E	Human	Esophagus	ESCC	4.57e-02	1.16e-01	0.0889
440567	UQCRHL	P9T-E	Human	Esophagus	ESCC	7.61e-07	1.32e-01	0.1131
440567	UQCRHL	P10T-E	Human	Esophagus	ESCC	1.02e-09	1.40e-01	0.116
440567	UQCRHL	P11T-E	Human	Esophagus	ESCC	3.17e-05	2.06e-01	0.1426
440567	UQCRHL	P15T-E	Human	Esophagus	ESCC	1.89e-05	1.75e-01	0.1149
440567	UQCRHL	P20T-E	Human	Esophagus	ESCC	2.31e-04	1.92e-01	0.1124
440567	UQCRHL	P21T-E	Human	Esophagus	ESCC	5.90e-20	4.41e-01	0.1617
440567	UQCRHL	P22T-E	Human	Esophagus	ESCC	2.01e-02	1.11e-01	0.1236
440567	UQCRHL	P23T-E	Human	Esophagus	ESCC	1.73e-06	2.60e-01	0.108
440567	UQCRHL	P24T-E	Human	Esophagus	ESCC	2.71e-05	1.19e-01	0.1287
440567	UQCRHL	P26T-E	Human	Esophagus	ESCC	1.77e-06	1.50e-01	0.1276
440567	UQCRHL	P27T-E	Human	Esophagus	ESCC	1.11e-07	1.81e-01	0.1055

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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

∗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:004603417	Endometrium	EEC	ATP metabolic process	107/2168	277/18723	1.32e-31	3.95e-28	107
GO:000611916	Endometrium	EEC	oxidative phosphorylation	71/2168	141/18723	5.89e-30	1.18e-26	71
GO:000906015	Endometrium	EEC	aerobic respiration	79/2168	189/18723	2.63e-26	3.95e-23	79
GO:004533315	Endometrium	EEC	cellular respiration	83/2168	230/18723	1.72e-22	2.06e-19	83
GO:004277315	Endometrium	EEC	ATP synthesis coupled electron transport	49/2168	95/18723	1.11e-21	9.50e-19	49
GO:004277515	Endometrium	EEC	mitochondrial ATP synthesis coupled electron transport	49/2168	95/18723	1.11e-21	9.50e-19	49
GO:001964615	Endometrium	EEC	aerobic electron transport chain	45/2168	87/18723	4.34e-20	3.26e-17	45
GO:001598015	Endometrium	EEC	energy derivation by oxidation of organic compounds	97/2168	318/18723	5.37e-20	3.58e-17	97
GO:002290415	Endometrium	EEC	respiratory electron transport chain	52/2168	114/18723	7.97e-20	4.78e-17	52
GO:000609115	Endometrium	EEC	generation of precursor metabolites and energy	125/2168	490/18723	3.76e-18	1.88e-15	125
GO:002290015	Endometrium	EEC	electron transport chain	61/2168	175/18723	4.60e-16	1.84e-13	61
GO:000612214	Endometrium	EEC	mitochondrial electron transport, ubiquinol to cytochrome c	9/2168	11/18723	1.63e-07	7.54e-06	9
GO:0006091110	Esophagus	ESCC	generation of precursor metabolites and energy	331/8552	490/18723	3.86e-23	8.45e-21	331
GO:0045333110	Esophagus	ESCC	cellular respiration	173/8552	230/18723	4.53e-20	5.99e-18	173
GO:0009060110	Esophagus	ESCC	aerobic respiration	145/8552	189/18723	2.16e-18	2.21e-16	145
GO:0015980110	Esophagus	ESCC	energy derivation by oxidation of organic compounds	220/8552	318/18723	1.20e-17	1.09e-15	220
GO:0022900110	Esophagus	ESCC	electron transport chain	133/8552	175/18723	2.18e-16	1.67e-14	133
GO:0046034111	Esophagus	ESCC	ATP metabolic process	189/8552	277/18723	1.99e-14	1.04e-12	189
GO:0006119111	Esophagus	ESCC	oxidative phosphorylation	106/8552	141/18723	8.19e-13	3.63e-11	106
GO:0022904110	Esophagus	ESCC	respiratory electron transport chain	89/8552	114/18723	1.36e-12	5.80e-11	89

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0502215	Liver	Cirrhotic	Pathways of neurodegeneration - multiple diseases	217/2530	476/8465	7.30e-14	2.03e-12	1.25e-12	217
hsa0501015	Liver	Cirrhotic	Alzheimer disease	180/2530	384/8465	5.52e-13	1.36e-11	8.36e-12	180
hsa0471415	Liver	Cirrhotic	Thermogenesis	121/2530	232/8465	5.70e-13	1.36e-11	8.36e-12	121
hsa0541515	Liver	Cirrhotic	Diabetic cardiomyopathy	108/2530	203/8465	1.99e-12	4.41e-11	2.72e-11	108
hsa0501222	Liver	HCC	Parkinson disease	198/4020	266/8465	9.40e-20	1.58e-17	8.76e-18	198
hsa0501622	Liver	HCC	Huntington disease	219/4020	306/8465	3.06e-18	3.42e-16	1.90e-16	219
hsa0501422	Liver	HCC	Amyotrophic lateral sclerosis	252/4020	364/8465	8.85e-18	7.41e-16	4.12e-16	252
hsa0520842	Liver	HCC	Chemical carcinogenesis - reactive oxygen species	167/4020	223/8465	2.85e-17	1.91e-15	1.06e-15	167
hsa0493242	Liver	HCC	Non-alcoholic fatty liver disease	124/4020	155/8465	4.54e-17	2.54e-15	1.41e-15	124
hsa0502022	Liver	HCC	Prion disease	195/4020	273/8465	3.26e-16	1.56e-14	8.67e-15	195
hsa0471422	Liver	HCC	Thermogenesis	170/4020	232/8465	5.36e-16	2.25e-14	1.25e-14	170
hsa0541522	Liver	HCC	Diabetic cardiomyopathy	151/4020	203/8465	2.72e-15	1.01e-13	5.63e-14	151
hsa0501022	Liver	HCC	Alzheimer disease	254/4020	384/8465	3.75e-14	8.97e-13	4.99e-13	254
hsa0019022	Liver	HCC	Oxidative phosphorylation	103/4020	134/8465	2.39e-12	5.01e-11	2.79e-11	103
hsa0502222	Liver	HCC	Pathways of neurodegeneration - multiple diseases	298/4020	476/8465	6.59e-12	1.30e-10	7.22e-11	298
hsa0501232	Liver	HCC	Parkinson disease	198/4020	266/8465	9.40e-20	1.58e-17	8.76e-18	198
hsa0501632	Liver	HCC	Huntington disease	219/4020	306/8465	3.06e-18	3.42e-16	1.90e-16	219
hsa0501432	Liver	HCC	Amyotrophic lateral sclerosis	252/4020	364/8465	8.85e-18	7.41e-16	4.12e-16	252
hsa0520852	Liver	HCC	Chemical carcinogenesis - reactive oxygen species	167/4020	223/8465	2.85e-17	1.91e-15	1.06e-15	167
hsa0493252	Liver	HCC	Non-alcoholic fatty liver disease	124/4020	155/8465	4.54e-17	2.54e-15	1.41e-15	124

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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

UQCRHL

SNV

Missense_Mutation

novel

c.13N>A

p.Asp5Asn

p.D5N

A0A096LP55

protein_coding

tolerated(0.12)

benign(0.1)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

UQCRHL

SNV

Missense_Mutation

novel

c.176C>G

p.Ser59Cys

p.S59C

A0A096LP55

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-VS-A950-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

UQCRHL

SNV

Missense_Mutation

rs774153442

c.244N>A

p.Val82Met

p.V82M

A0A096LP55

protein_coding

tolerated(0.06)

benign(0.037)

TCGA-A5-A0G9-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

UQCRHL

SNV

Missense_Mutation

novel

c.195G>T

p.Glu65Asp

p.E65D

A0A096LP55

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-B5-A11E-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

UQCRHL

SNV

Missense_Mutation

rs780112142

c.179N>A

p.Arg60Gln

p.R60Q

A0A096LP55

protein_coding

tolerated(0.06)

benign(0.01)

TCGA-B5-A1MR-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

UQCRHL

SNV

Missense_Mutation

rs764654397

c.34G>A

p.Glu12Lys

p.E12K

A0A096LP55

protein_coding

tolerated(0.88)

benign(0.035)

TCGA-EO-A22X-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unspecific

Carboplatin

Complete Response

UQCRHL

SNV

Missense_Mutation

novel

c.86N>A

p.Pro29His

p.P29H

A0A096LP55

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-EO-A3KX-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

UQCRHL

insertion

Nonsense_Mutation

novel

c.31_32insAATAAGAAACAAATGGTACAT

p.Thr11delinsLysTerGluThrAsnGlyThrSer

p.T11delinsK*ETNGTS

A0A096LP55

protein_coding

TCGA-BS-A0UJ-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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