# Expression Profiles and Biomarker Potential of Long Non-Coding RNAs H19, NEAT1, MALAT1 and HOTAIR in Locally Advanced Rectal Cancer Patients

**Authors:** Katarina Eric, Jovana Rosic Stojkovic, Marko Miladinov, Sandra Dragicevic, Goran Barisic, Velimir Markovic, Katarina Zeljic

PMC · DOI: 10.3390/ijms27041672 · 2026-02-09

## TL;DR

This study investigates the potential of four long non-coding RNAs as biomarkers for locally advanced rectal cancer, finding that H19 shows promise for diagnosis but not for predicting treatment response.

## Contribution

The study evaluates the diagnostic, prognostic, and predictive potential of H19, NEAT1, MALAT1, and HOTAIR in locally advanced rectal cancer for the first time.

## Key findings

- H19 showed significantly higher expression in tumor tissue and moderate potential to distinguish tumor from non-tumor tissue.
- NEAT1 and MALAT1 also showed altered expression in tumor and non-tumor tissues before and after treatment.
- None of the lncRNAs were significantly predictive of treatment response due to limited responders in the study.

## Abstract

Locally advanced rectal cancer (LARC) presents a clinical challenge due to lack of reliable molecular biomarkers for early diagnosis, prognosis, and prediction of response to neoadjuvant chemoradiotherapy (nCRT). Long non-coding RNAs (lncRNAs) have emerged as promising candidates due to their characteristics and regulatory roles. H19, NEAT1, MALAT1 and HOTAIR are lncRNAs deregulated in gastrointestinal cancers, with insufficient data on their biomarker potential in LARC. The study aimed to analyze the diagnostic, prognostic and predictive utility of H19, NEAT1, MALAT1 and HOTAIR in LARC. Relative expression was evaluated by RT-qPCR in tumor and non-tumor tissues from 25 LARC patients before and after nCRT. H19, NEAT1, and MALAT1 showed significantly altered expression in tumor tissue, as well as non-tumor tissue before and after nCRT. H19 expression was significantly higher in tumor vs. non-tumor tissue before treatment and demonstrated moderate potential to discriminate between tumor and non-tumor. None of the lncRNAs showed statistically significant predictive values for nCRT response or association with treatment outcomes in our study, which was limited by the small number of responders. Our results suggest that H19 might be considered as a potential therapeutic target in LARC. Further studies with larger patient groups are required to confirm its diagnostic and prognostic utility.

## Linked entities

- **Genes:** H19 (H19 imprinted maternally expressed transcript) [NCBI Gene 283120], NEAT1 (nuclear paraspeckle assembly transcript 1) [NCBI Gene 283131], MALAT1 (metastasis associated lung adenocarcinoma transcript 1) [NCBI Gene 378938], HOTAIR (HOX transcript antisense RNA) [NCBI Gene 100124700]
- **Diseases:** rectal cancer (MONDO:0006519)

## Full-text entities

- **Genes:** GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, NEAT1 (nuclear paraspeckle assembly transcript 1) [NCBI Gene 283131] {aka LINC00084, NCRNA00084, TP53LC15, TncRNA, VINC}, MIR34A (microRNA 34a) [NCBI Gene 407040] {aka MIRN34A, miRNA34A, mir-34, mir-34a}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, HOTAIR (HOX transcript antisense RNA) [NCBI Gene 100124700] {aka HOXAS, HOXC-AS4, HOXC11-AS1, NCRNA00072}, TENM1 (teneurin transmembrane protein 1) [NCBI Gene 10178] {aka ODZ1, ODZ3, TEN-M1, TEN1, TNM, TNM1}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, CCL20 (C-C motif chemokine ligand 20) [NCBI Gene 6364] {aka CKb4, Exodus, LARC, MIP-3-alpha, MIP-3a, MIP3A}, MALAT1 (metastasis associated lung adenocarcinoma transcript 1) [NCBI Gene 378938] {aka HCN, LINC00047, NCRNA00047, NEAT2, PRO2853, miPEP-52}, H19 (H19 imprinted maternally expressed transcript) [NCBI Gene 283120] {aka ASM, ASM1, BWS, D11S813E, GMRSP, LINC00008}, CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}
- **Diseases:** necrosis (MESH:D009336), cancers of the gastrointestinal tract (MESH:D005770), cTNM (MESH:D008207), mucinous adenocarcinoma of the rectum (MESH:D002288), death (MESH:D003643), CRC (MESH:D015179), tumorigenesis (MESH:D063646), gastric cancer (MESH:D013274), LARC (MESH:D012004), Cancer (MESH:D009369), READ (MESH:D000230), injury to (MESH:D014947), inflammation (MESH:D007249), prostate cancer (MESH:D011471)
- **Chemicals:** TRIzolTM Reagent (-), leucovorin (MESH:D002955), 5-FU (MESH:D005472)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12940164/full.md

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Source: https://tomesphere.com/paper/PMC12940164