Evidence map›Paper›PMID 38774453›Full record

ArticleOncology letters2024

NKX2‑1 copy number alterations are associated with oncogenic, immunological and prognostic remodeling in non‑small cell lung cancer.

Herdee Gloriane C Luna, Marcelo Severino Imasa, Necy Juat, Katherine V Hernandez, Treah May Sayo, Gloria Cristal-Luna, Sheena Marie Asur-Galang, Mirasol Bellengan, Kent John Duga, Bien Brian Buenaobra and 5 more

Abstract read
In one paragraph

Article in Oncology letters, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. 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

15 authors.

Herdee Gloriane C LunaDepartment of Medical Oncology, Lung Center of The Philippines, Quezon City, Metro Manila 1100, Philippines.
Marcelo Severino ImasaDepartment of Medical Oncology, Lung Center of The Philippines, Quezon City, Metro Manila 1100, Philippines.
Necy JuatDepartment of Internal Medicine, Section of Medical Oncology, National Kidney and Transplant Institute, Quezon City, Metro Manila 1101, Philippines.
Katherine V HernandezDepartment of Internal Medicine, Section of Oncology, East Avenue Medical Center, Quezon City, Metro Manila 1100, Philippines.
Treah May SayoDepartment of Pathology and Laboratory Medicine, Lung Center of The Philippines, Quezon City, Metro Manila 1100, Philippines.
Gloria Cristal-LunaDepartment of Internal Medicine, Section of Medical Oncology, National Kidney and Transplant Institute, Quezon City, Metro Manila 1101, Philippines.
Sheena Marie Asur-GalangClinical Proteomics for Cancer Initiative, Department of Science and Technology-Philippine Council for Health Research and Development, Taguig, Metro Manila 1631, Philippines.
Mirasol BellenganClinical Proteomics for Cancer Initiative, Department of Science and Technology-Philippine Council for Health Research and Development, Taguig, Metro Manila 1631, Philippines.
Kent John DugaClinical Proteomics for Cancer Initiative, Department of Science and Technology-Philippine Council for Health Research and Development, Taguig, Metro Manila 1631, Philippines.
Bien Brian BuenaobraClinical Proteomics for Cancer Initiative, Department of Science and Technology-Philippine Council for Health Research and Development, Taguig, Metro Manila 1631, Philippines.
Marvin I De Los SantosClinical Proteomics for Cancer Initiative, Department of Science and Technology-Philippine Council for Health Research and Development, Taguig, Metro Manila 1631, Philippines.
Daniel MedinaClinical Proteomics for Cancer Initiative, Department of Science and Technology-Philippine Council for Health Research and Development, Taguig, Metro Manila 1631, Philippines.
Jamirah SamoClinical Proteomics for Cancer Initiative, Department of Science and Technology-Philippine Council for Health Research and Development, Taguig, Metro Manila 1631, Philippines.
Venus Minerva LiteralClinical Proteomics for Cancer Initiative, Department of Science and Technology-Philippine Council for Health Research and Development, Taguig, Metro Manila 1631, Philippines.
Sullian Sy-NavalDepartment of Medical Oncology, Lung Center of The Philippines, Quezon City, Metro Manila 1100, Philippines.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

NK2 homeobox 1 (NKX2-1) copy number alterations (CNAs) are frequently observed in lung cancer. However, little is known about the complete landscape of focal alterations in NKX2-1 copy number (CN), their clinical significance and their therapeutic implications in non-small cell lung cancer (NSCLC). The correlations between NKX2-1 expression and EGFR driver mutations and programmed death ligand 1 (PD-L1) co-expression were studied using immunohistochemistry and PCR from the tumors of recruited Filipino patients (n=45). Clinical features of NSCLC with NKX2-1 CNAs were resolved at the tumor and clonal levels using the molecular profiles of patients with lung adenocarcinoma and lung squamous cell carcinoma from The Cancer Genome Atlas (n=1,130), and deconvoluted single-cell RNA-seq data from the Bivona project (n=1,654), respectively. Despite a significant and positive correlation between expression and CN (r=0.264; P<0.001), NKX2-1 CNAs exerted a stronger influence on the combined EGFR and PD-L1 status of NSCLC tumors than expression. NKX2-1 CN gain was prognostic of favorable survival (P=0.018) and a better response to targeted therapy. NKX2-1 CN loss predicted a worse survival (P=0.041). Mutational architecture in the Y-chromosome differentiated the two prognostic groups. There were 19,941 synonymous mutations and 1,408 genome-wide CN perturbations associated with NKX2-1 CNAs. Tumors with NKX2-1 CN gain expressed lymphocyte markers more heterogeneously than those with CN loss. Higher expression of tumor-infiltrating lymphocyte gene signatures in CN gain was prognostic of longer disease-free survival (P=0.005). Tumors with NKX2-1 CN gain had higher B-cell (P<0.001) and total T-cell estimates (P=0.003). NKX2-1 CN loss was associated with immunologically colder tumors due to higher M2 macrophage infiltrates (P=0.011) and higher expression of immune checkpoint proteins, CD274 (P=0.025), VTCN1 (P<0.001) and LGALS9 (P=0.002). In conclusion, NKX2-1 CNAs are associated with tumors that exhibit clinically diverse characteristics, and with unique oncogenic, immunological and prognostic signatures.

Indexed as

chromosomal instabilitycopy number alterationlymphocyte infiltrationNK2 homeobox 1non-small cell lung cancerthyroid transcription factor 1

Identifiers

PMID38774453
PMCPMC11106692

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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.