# Comprehensive bioinformatic analysis of HTR7: A potential biomarker for diagnosis, survival, and immunotherapy in pan-cancer

**Authors:** Yuhao Yao, Xiao Xia, Lanxin Zhang, Hongtai Xiong, Size Li, Wei Hou

PMC · DOI: 10.1371/journal.pone.0335398 · 2025-11-14

## TL;DR

This study explores HTR7's role across various cancers, showing its potential as a diagnostic and prognostic biomarker and its link to immune cell infiltration and drug sensitivity.

## Contribution

The study provides a comprehensive pan-cancer analysis of HTR7's expression, prognosis, immunotherapy relevance, and pathway involvement.

## Key findings

- HTR7 is highly expressed in 12 tumors and lowly expressed in 13 tumors compared to normal tissues.
- High HTR7 expression correlates with favorable or unfavorable prognosis depending on cancer type.
- HTR7 expression is linked to immune cell infiltration and drug sensitivity in various cancers.

## Abstract

We used several public databases to perform a comprehensive pan-cancer analysis to determine the potential role of HTR7 in diagnosing tumors, predicting prognosis, and predicting cancer immunotherapy response. The results showed that HTR7 is highly expressed in 12 tumors and lowly expressed in 13 tumors compared with normal tissues. HTR7 has a specific diagnostic value in 18 cancers, especially in COAD, HNSC, KIRC, PCPG, and READ. High expression of HTR7 was associated with a favorable prognosis in ACC, COAD, KIRC, KIRP, PRAD, READ, SKCM, and THCA, while in CESC, ESCA, GBM, HNSC, PAAD, and THYM, high expression of HTR7 was associated with an unfavorable prognosis. In most tumors, HTR7 expression was positively correlated with the infiltration of monocytes, macrophages, and myeloid dendritic cells and negatively correlated with Th1 infiltration. We found that HTR7 expression was positively correlated with CD274, CTLA-4, HAVCR2, PDCD1, PDCD1LG2, and TIGIT in numerous tumors. Furthermore, our study showed that aberrant methylation of HTR7 was associated with the infiltration of many immune cells, including Th1, Th17, DC, macrophages, etc. In cancer pathways, HTR7 could inhibit the cell cycle, DNA damage, and hormone AR pathways and activate the EMT and RAS/MAPK pathways. GO and KEGG enrichment analyses revealed that HTR7 could participate in the G protein-coupled receptor signaling pathway, serotonin receptor signaling pathway, hormone signaling, cAMP signaling pathway, etc. Several drugs, including 5-fluorouracil, gemcitabine, sunitinib, tipifarnib, and trametinib, may be sensitive to high HTR7 expression in tumors.

## Linked entities

- **Genes:** HTR7 (5-hydroxytryptamine receptor 7) [NCBI Gene 3363], CD274 (CD274 molecule) [NCBI Gene 29126], CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493], HAVCR2 (hepatitis A virus cellular receptor 2) [NCBI Gene 84868], PDCD1 (programmed cell death 1) [NCBI Gene 5133], PDCD1LG2 (programmed cell death 1 ligand 2) [NCBI Gene 80380], TIGIT (T cell immunoreceptor with Ig and ITIM domains) [NCBI Gene 201633]
- **Chemicals:** 5-fluorouracil (PubChem CID 3385), gemcitabine (PubChem CID 60750), sunitinib (PubChem CID 5329102), tipifarnib (PubChem CID 159324), trametinib (PubChem CID 11707110)
- **Diseases:** ACC (MONDO:0006639), COAD (MONDO:0002271), PRAD (MONDO:0005082), READ (MONDO:0002169), CESC (MONDO:0006143), GBM (MONDO:0018177), PAAD (MONDO:0006047), THYM (MONDO:0006456)

## Full-text entities

- **Genes:** HAVCR2 (hepatitis A virus cellular receptor 2) [NCBI Gene 84868] {aka CD366, HAVcr-2, KIM-3, SPTCL, TIM3, TIMD-3}, PDCD1LG2 (programmed cell death 1 ligand 2) [NCBI Gene 80380] {aka B7DC, Btdc, CD273, PD-L2, PDCD1L2, PDL2}, LPAR2 (lysophosphatidic acid receptor 2) [NCBI Gene 9170] {aka EDG-4, EDG4, LPA-2, LPA2}, HTR7 (5-hydroxytryptamine receptor 7) [NCBI Gene 3363] {aka 5-HT7}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, TIGIT (T cell immunoreceptor with Ig and ITIM domains) [NCBI Gene 201633] {aka VSIG9, VSTM3, WUCAM}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}
- **Diseases:** GBM (MESH:D005910), COAD (MESH:D029424), cancer (MESH:D009369), ACC (MESH:D004476)
- **Chemicals:** trametinib (MESH:C560077), cAMP (-), gemcitabine (MESH:D000093542), 5-fluorouracil (MESH:D005472), sunitinib (MESH:D000077210), tipifarnib (MESH:C402769)

## Figures

13 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12617886/full.md

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Source: https://tomesphere.com/paper/PMC12617886