Evidence map›Paper›PMID 38741920›Full record

ArticleLung Cancer (Auckland, N.Z.)2024

HMGB1 Expression Levels Correlate with Response to Immunotherapy in Non-Small Cell Lung Cancer.

Maria González-Cao, Xueting Cai, Jilian Wilhelmina Paulina Bracht, Xuan Han, Yang Yang, Carlos Pedraz-Valdunciel, Teresa Morán, Javier García-Corbacho, Andrés Aguilar, Reyes Bernabé and 9 more

Abstract read
In one paragraph

Article in Lung Cancer (Auckland, N.Z.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Maria González-CaoTranslational Cancer Research Unit, Instituto Oncológico Dr Rosell, Dexeus University Hospital, Barcelona, Spain.
Xueting CaiIntegrated Traditional Chinese and Western Medicine Department of Affiliated Hospital, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People's Republic of China.
Jilian Wilhelmina Paulina BrachtAmsterdam University Medical Center (UMC), Amsterdam, The Netherlands.ORCID 0000-0001-9552-3960
Xuan HanIntegrated Traditional Chinese and Western Medicine Department of Affiliated Hospital, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People's Republic of China.
Yang YangIntegrated Traditional Chinese and Western Medicine Department of Affiliated Hospital, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People's Republic of China.
Carlos Pedraz-ValduncielLaboratory of Oncology, Pangaea Oncology, Quirón Dexeus University Hospital, Barcelona, Spain.
Teresa MoránMedical Oncology Department, Catalan Institute of Oncology (ICO), Germans Trias i Pujol Hospital, Badalona, Spain.
Javier García-CorbachoMedical Oncology Department (Hospital Clinic)/Translational Genomics and Targeted Therapies in Solid Tumors (IDIBAPs), Barcelona, Spain.
Andrés AguilarTranslational Cancer Research Unit, Instituto Oncológico Dr Rosell, Dexeus University Hospital, Barcelona, Spain.
Reyes BernabéMedical Oncology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain.ORCID 0000-0003-0312-9195
Pedro De MarchiMolecular Oncology Research Center; Barretos Cancer Hospital, Barretos, Brazil.
Luciane Sussuchi da SilvaMolecular Oncology Research Center; Barretos Cancer Hospital, Barretos, Brazil.ORCID 0000-0002-7470-4655
Leticia Ferro LealMolecular Oncology Research Center; Barretos Cancer Hospital, Barretos, Brazil.
Rui Manuel ReisMolecular Oncology Research Center; Barretos Cancer Hospital, Barretos, Brazil.ORCID 0000-0002-9639-7940
Jordi Codony-ServatLaboratory of Oncology, Pangaea Oncology, Quirón Dexeus University Hospital, Barcelona, Spain.
Eloisa Jantus-LewintreValencian Community Foundation Principe Felipe Research Center, Laboratory of Molecular Oncology, Valencia, Spain.ORCID 0000-0001-7395-4380
Miguel Angel Molina-VilaLaboratory of Oncology, Pangaea Oncology, Quirón Dexeus University Hospital, Barcelona, Spain.
Peng CaoIntegrated Traditional Chinese and Western Medicine Department of Affiliated Hospital, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People's Republic of China.
Rafael RosellTranslational Cancer Research Unit, Instituto Oncológico Dr Rosell, Dexeus University Hospital, Barcelona, Spain.ORCID 0000-0003-0817-3400

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: High-mobility group box 1 protein (HMGB1) is subject to exportin 1 (XPO1)-dependent nuclear export, and it is involved in functions implicated in resistance to immunotherapy. We investigated whether HMGB1 mRNA expression was associated with response to immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC). Patients and Methods: RNA was isolated from pretreatment biopsies of patients with advanced NSCLC treated with ICI. Gene expression analysis of several genes, including HMGB1, was conducted using the NanoString Counter analysis system (PanCancer Immune Profiling Panel). Western blotting analysis and cell viability assays in EGFR and KRAS mutant cell lines were carried out. Evaluation of the antitumoral effect of ICI in combination with XPO1 blocker (selinexor) and trametinib was determined in a murine Lewis lung carcinoma model. Results: HMGB1 mRNA levels in NSCLC patients treated with ICI correlated with progression-free survival (PFS) (median PFS 9.0 versus 18.0 months, P=0.008, hazard ratio=0.30 in high versus low HMGB1). After TNF-α stimulation, HMGB1 accumulates in the cytoplasm of PC9 cells, but this accumulation can be prevented by using selinexor or antiretroviral drugs. Erlotinib or osimertinib with selinexor in EGFR-mutant cells and trametinib plus selinexor in KRAS mutant abolish tumor cell proliferation. Selinexor with a PD-1 inhibitor with or without trametinib abrogates the tumor growth in the murine Lewis lung cancer model. Conclusion: An in-depth exploration of the functions of HMGB1 mRNA and protein is expected to uncover new potential targets and provide a basis for treating metastatic NSCLC in combination with ICI.

Indexed as

HMGB1immunotherapyK-Ras mutationsLewis lung cancer murine modelnon-small cell lung cancer

Identifiers

PMID38741920
PMCPMC11090191

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.