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pmid:36776001

Development of lactate-related gene signature and prediction of overall survival and chemosensitivity in patients with colorectal cancer.

Zhi Tong · Xinyu Wang · Sanbao Shi · Tiewei Hou · Guangrong Gao · Da Li · Yongqi Shan · Cheng Zhang

Cancer medicine · 2023 doi:10.1002/cam4.5682

Paper

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pmid:36776001
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title
Development of lactate-related gene signature and prediction of overall survival and chemosensitivity in patients with colorectal cancer.
doi
10.1002/cam4.5682
pmid
36776001
authors array · 8 items
[0]
Zhi Tong
[1]
Xinyu Wang
[2]
Sanbao Shi
[3]
Tiewei Hou
[4]
Guangrong Gao
[5]
Da Li
[6]
Yongqi Shan
[7]
Cheng Zhang
journal
Cancer medicine
year
2023
abstract
BACKGROUND: Colorectal cancer (CRC) is a malignant tumor of the digestive system that contains high levels of immune cells. Lactic acid, a major metabolite, plays a crucial role in tumor development, maintenance, and therapeutic response. However, the prognostic potential and therapeutic biomarker potential of lactate-related genes (LRGs) in CRC patients remain to be elucidated. METHODS: We collected the mRNA expression profile and clinical data of CRC patients from the Cancer Genome Atlas (TCGA) database and the GSE59382 cohort. Univariate Cox regression, Lasso regression and multivariate Cox regression analysis were used to construct the prognosis model. Combined with the risk score and important clinicopathological features, the nomogram was established. In addition, the relationship between risk score and immune infiltration, immune checkpoint gene expression, and drug sensitivity was investigated. RESULTS: We constructed lactate-related gene signatures (LRGS) based on four LRGs, which independently predicted the prognosis of CRC. Patients with different risk scores are found to have distinct immune status, tumor mutation load, immune response, and drug sensitivity. In addition, nomogram results determined by risk scores and clinical factors have higher predictive performance. CONCLUSION: We found that LRGS is a reliable biomarker for predicting clinical outcomes, evaluating immune infiltration and efficacy, and predicting the sensitivity to drugs in patients with CRC.
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According to the combined univariate and multivariate Cox regression analysis, the LRGS model predicted the OS independently (HR 1.550, 95% CI 1.363–1.761, P 2.44 E‐06) (Figure 4A,B); the result was confirmed by analyzing the GEO cohort (Figure 4C,D).
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sections[18] "Prognostic significance of LRGS" paragraph 4
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According to the combined univariate and multivariate Cox regression analysis, the LRGS model predicted the OS independently (HR 1.550, 95% CI 1.363–1.761, P 2.44 E‐06) (Figure 4A,B); the result was confirmed by analyzing the GEO cohort (Figure 4C,D).
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The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
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sections[31] "DATA AVAILABILITY STATEMENT" paragraph 2
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The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
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The lactate-related gene signature independently predicted overall survival in colorectal cancer (HR 1.550, 95% CI 1.363–1.761, P 2.44 E−06).
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According to the combined univariate and multivariate Cox regression analysis, the LRGS model predicted the OS independently (HR 1.550, 95% CI 1.363–1.761, P 2.44 E‐06) (Figure 4A,B); the result was confirmed by analyzing the GEO cohort (Figure 4C,D).
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sections[18] "Prognostic significance of LRGS" paragraph 4
quote
According to the combined univariate and multivariate Cox regression analysis, the LRGS model predicted the OS independently (HR 1.550, 95% CI 1.363–1.761, P 2.44 E‐06) (Figure 4A,B); the result was confirmed by analyzing the GEO cohort (Figure 4C,D).
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The lactate-related gene signature independently predicted overall survival in colorectal cancer (HR 1.550, 95% CI 1.363–1.761, P 2.44 E−06).
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GSM972409
[472]
GSM972410
[473]
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[474]
GSM972412
[475]
GSM972413
[476]
GSM972414
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GSM972425
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GSM972426
[489]
GSM972427
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GSM972428
[491]
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[492]
GSM972430
[493]
GSM972431
[494]
GSM972432
[495]
GSM972433
[496]
GSM972434
[497]
GSM972435
[498]
GSM972436
[499]
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[500]
GSM972438
[501]
GSM972439
[502]
GSM972440
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GSM972441
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GSM972442
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GSM972443
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GSM972444
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GSM972445
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GSM972446
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GSM972447
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GSM972448
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GSM972451
[514]
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GSM972455
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GSM972456
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GSM972458
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GSM972460
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GSM972461
[524]
GSM972462
[525]
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[526]
GSM972464
[527]
GSM972465
[528]
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[529]
GSM972467
[530]
GSM972468
[531]
GSM972469
[532]
GSM972470
[533]
GSM972471
[534]
GSM972472
[535]
GSM972473
[536]
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[537]
GSM972475
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GSM972478
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[563]
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GSM972520
[583]
GSM972521
[584]
GSM972522
sample_count
585
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Gene expression Classification of Colon Cancer defines six molecular subtypes with distinct clinical, molecular and survival characteristics [Expression]
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
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[2] object · 15 fields
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data:geo:GSE59382
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https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE59382
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null
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null
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null
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GSE59382
version
null
note
The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
access_statement_kind
data_availability_statement
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[0]
GSM1436087
[1]
GSM1436088
[2]
GSM1436089
[3]
GSM1436090
sample_count
4
group_sizes
null
group_sizes_basis
null
platform
6883
taxon
Homo sapiens
title
Alteration of gene expression in MCF-7 cells induced by king cobra venom L-amino acid oxidase (OH-LAAO)
resolution_checked_at
2026-11-01T18:46:34Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 4 items
[0]
asset:data:geo:GSE39582 not downloaded
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asset:data:geo:GSE39582 licence not read
[2]
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[3]
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analysis object · 4 fields
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partial
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[0] object · 10 fields
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method-1
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survival_analysis
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cox_proportional_hazards
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Survival analysis
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cox_ph
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parameters object · 0 fields
data_shapes array · 1 item
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time_to_event_with_censoring
evidence object · 3 fields
score
1
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verbatim
quote
According to the combined univariate and multivariate Cox regression analysis, the LRGS model predicted the OS independently (HR 1.550, 95% CI 1.363–1.761, P 2.44 E‐06) (Figure 4A,B); the result was confirmed by analyzing the GEO cohort (Figure 4C,D).
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id
method-2
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[0]
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welch_t
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group_comparison_anova
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data_shapes array · 1 item
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two_or_more_groups_continuous
evidence object · 3 fields
score
0.8
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high
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analysis of variance
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[0] object · 8 fields
id
target-published-estimate
claim_id
claim-target-result
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bootstrap_mean_difference
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per cent
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null
state
complete
note
The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none.
[1] object · 8 fields
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claim-target-result
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hazard ratio
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null
state
complete
note
The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none.
gaps array · 1 item
[0]
method.reader_differs_from_extractor
capability object · 3 fields
state
complete
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[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
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meta_analysis
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gwas
candidate
Automated Assays Laravel application and simulated adapters
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readiness object · 8 fields
state
complete
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R1
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nothing:replicable_now
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method object · 5 fields
tier
R1
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true
required_operations array · 1 item
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cox_ph
missing_operations array · 0 items
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 2 items
[0]
GSE39582
[1]
GSE59382
resolved_accessions array · 2 items
[0]
GSE39582
[1]
GSE59382
statements array · 1 item
[0]
The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
basis
The paper names GSE39582, GSE59382 in Gene Expression Omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 1 item
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cox_ph
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[0]
source:pmid:36776001
[1]
data:geo:GSE39582
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run_analysis
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[0]
data:geo:GSE39582
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review object · 5 fields
state
partial
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extraction_review
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MiniMax-M3.1-Flash
provider
minimax
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minimax
read_at
2026-11-01T18:27:06Z
independence
single_reader
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method
verbatim
availability
verbatim
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5
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11003
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2022
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128
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[0] object · 4 fields
id
extraction
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complete
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MiniMax-M3.1-Flash
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minimax
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review.human_critique
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absent
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not_run
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null
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execution.not_run
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pmid:36776001
type
paper
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pmid:36776001
[1] object · 3 fields
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source:pmid:36776001
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manuscript
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PMID 36776001 full text
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id
data:geo:GSE39582
type
dataset
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GEO GSE39582
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[0] object · 4 fields
id
activity-reading-sci-2026-11-01
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classification
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source:pmid:36776001
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PMID 36776001 full text
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GEO GSE39582
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agent:corpus-assay-engine
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activity-resolve-GSE39582
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data:geo:GSE39582
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Iseq, McP‐counter, xCELL, ESTIMATE, IPS, and EPIC algorithms to compare differences in immune
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According to the combined univariate and multivariate Cox regression analysis, the LRGS model predicted the OS independently (HR 1.550, 95% CI 1.363–1.761, P 2.44 E‐06) (Figure 4A,B); the result was confirmed by analyzing the GEO cohort (Figure 4C,D).
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36776001", "kind": "science-record", "revision": 3, "content_hash": "sha256:61a1953b38f1a5eea38fbe26240a696ef0676b44baa3f24fb55c382d9a76fe37", "created_at": "2026-11-01T19:01:21Z", "updated_at": "2026-11-01T22:08:47Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Development of lactate-related gene signature and prediction of overall survival and chemosensitivity in patients with colorectal cancer.", "doi": "10.1002/cam4.5682", "pmid": "36776001", "authors": ["Zhi Tong", "Xinyu Wang", "Sanbao Shi", "Tiewei Hou", "Guangrong Gao", "Da Li", "Yongqi Shan", "Cheng Zhang"], "journal": "Cancer medicine", "year": 2023, "abstract": "BACKGROUND: Colorectal cancer (CRC) is a malignant tumor of the digestive system that contains high levels of immune cells. Lactic acid, a major metabolite, plays a crucial role in tumor development, maintenance, and therapeutic response. However, the prognostic potential and therapeutic biomarker potential of lactate-related genes (LRGs) in CRC patients remain to be elucidated.\nMETHODS: We collected the mRNA expression profile and clinical data of CRC patients from the Cancer Genome Atlas (TCGA) database and the GSE59382 cohort. Univariate Cox regression, Lasso regression and multivariate Cox regression analysis were used to construct the prognosis model. Combined with the risk score and important clinicopathological features, the nomogram was established. In addition, the relationship between risk score and immune infiltration, immune checkpoint gene expression, and drug sensitivity was investigated.\nRESULTS: We constructed lactate-related gene signatures (LRGS) based on four LRGs, which independently predicted the prognosis of CRC. Patients with different risk scores are found to have distinct immune status, tumor mutation load, immune response, and drug sensitivity. In addition, nomogram results determined by risk scores and clinical factors have higher predictive performance.\nCONCLUSION: We found that LRGS is a reliable biomarker for predicting clinical outcomes, evaluating immune infiltration and efficacy, and predicting the sensitivity to drugs in patients with CRC.", "claims": [{"id": "claim-method", "statement": "According to the combined univariate and multivariate Cox regression analysis, the LRGS model predicted the OS independently (HR 1.550, 95% CI 1.363–1.761, P 2.44 E‐06) (Figure 4A,B); the result was confirmed by analyzing the GEO cohort (Figure 4C,D).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36776001", "locator": "sections[18] \"Prognostic significance of LRGS\" paragraph 4", "quote": "According to the combined univariate and multivariate Cox regression analysis, the LRGS model predicted the OS independently (HR 1.550, 95% CI 1.363–1.761, P 2.44 E‐06) (Figure 4A,B); the result was confirmed by analyzing the GEO cohort (Figure 4C,D)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36776001", "locator": "sections[31] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The lactate-related gene signature independently predicted overall survival in colorectal cancer (HR 1.550, 95% CI 1.363–1.761, P 2.44 E−06).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "According to the combined univariate and multivariate Cox regression analysis, the LRGS model predicted the OS independently (HR 1.550, 95% CI 1.363–1.761, P 2.44 E‐06) (Figure 4A,B); the result was confirmed by analyzing the GEO cohort (Figure 4C,D)."}, "evidence": [{"asset": "source:pmid:36776001", "locator": "sections[18] \"Prognostic significance of LRGS\" paragraph 4", "quote": "According to the combined univariate and multivariate Cox regression analysis, the LRGS model predicted the OS independently (HR 1.550, 95% CI 1.363–1.761, P 2.44 E‐06) (Figure 4A,B); the result was confirmed by analyzing the GEO cohort (Figure 4C,D)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The lactate-related gene signature independently predicted overall survival in colorectal cancer (HR 1.550, 95% CI 1.363–1.761, P 2.44 E−06).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36776001"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE39582"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE39582"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36776001", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1002/cam4.5682", "sha256": "sha256:938f206af01efa3928d0176843b2e2293aa38e045f86ed57ecb1de9f7d2c4e17", "bytes": 41004, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1002/cam4.5682", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10166923", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE39582", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39582", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE39582", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material. 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