# Expression and Clinical Significance of MAPK8, MAPK9, MAP2K4, and MAP2K7 Genes in Colorectal Cancer

**Authors:** Agnieszka Wosiak, Damian Wodziński, Rafał Świechowski, Jacek Pietrzak, Michał Mik, Ewa Balcerczak

PMC · DOI: 10.3390/ijms27010100 · International Journal of Molecular Sciences · 2025-12-22

## TL;DR

This study explores how changes in specific genes related to the JNK signaling pathway are linked to the development and progression of colorectal cancer.

## Contribution

The study identifies distinct expression patterns and clinical roles of MAPK8, MAPK9, MAP2K4, and MAP2K7 in colorectal cancer.

## Key findings

- MAP2K7 gene expression was significantly higher in tumors with higher histological grades.
- Elevated MAPK8 gene expression was associated with increased regional lymph node metastasis.
- MAPK9 and MAP2K4 may play protective roles in early stages of the disease.

## Abstract

This study investigated whether alterations in the expression of genes integral to the c-Jun N-terminal kinase (JNK) signaling pathway play a role in the pathogenesis of colorectal cancer (CRC). It analyzed the expression of genes encoding two JNK isoforms (MAPK8 and MAPK9) and the JNK-activating kinases (MAP2K4 and MAP2K7). Gene expression patterns in CRC tissue were compared with existing data in public online databases to provide an integrated understanding of their potential role in tumorigenesis. The material consisted of 55 cancer tissue fragments collected intraoperatively from patients with histopathologically confirmed CRC. Total RNA isolated from these tissues was used to determine the relative expression of the selected genes using quantitative PCR. Additionally, data from publicly accessible bioinformatics databases were utilized. MAP2K7 gene expression was significantly elevated in tumor specimens with higher histological grades. Conversely, MAPK9 gene expression tended to be higher in tumor tissues with lower histological grades. Moreover, elevated MAPK8 gene expression was linked to an increased incidence of regional lymph node metastasis. Furthermore, bioinformatics analysis confirmed that MAP2K7 and MAPK8 appear to promote tumor aggressiveness and metastasis, whereas MAPK9 and MAP2K4 may have a protective or regulatory role in early stages of the disease.

## Linked entities

- **Genes:** MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599], MAPK9 (mitogen-activated protein kinase 9) [NCBI Gene 5601], MAP2K4 (mitogen-activated protein kinase kinase 4) [NCBI Gene 6416], MAP2K7 (mitogen-activated protein kinase kinase 7) [NCBI Gene 5609]
- **Diseases:** colorectal cancer (MONDO:0005575)

## Full-text entities

- **Genes:** MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, MAP2K7 (mitogen-activated protein kinase kinase 7) [NCBI Gene 5609] {aka JNKK2, MAPKK7, MEK, MEK 7, MKK7, PRKMK7}, MAPK9 (mitogen-activated protein kinase 9) [NCBI Gene 5601] {aka JNK-55, JNK2, JNK2A, JNK2ALPHA, JNK2B, JNK2BETA}, MAP2K4 (mitogen-activated protein kinase kinase 4) [NCBI Gene 6416] {aka JNKK, JNKK1, MAPKK4, MEK4, MKK4, PRKMK4}
- **Diseases:** lymph node metastasis (MESH:D008207), metastasis (MESH:D009362), CRC (MESH:D015179), cancer (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12785643/full.md

## References

24 references — full list in the complete paper: https://tomesphere.com/paper/PMC12785643/full.md

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Source: https://tomesphere.com/paper/PMC12785643