5-Hydroxytryptamine G-Protein-Coupled Receptor Family Genes - Key Players in Cancer Prognosis, Immune Regulation, and Therapeutic Response

Sep 21, 2026

Uploaded by Theodora

5-hydroxytryptamine G-protein-coupled receptors (HTGPCRs), comprising 13 genes, are linked to cancer progression, yet their integrated roles remain insufficiently defined. Gene-expression profiling across pan-cancer was used to evaluate prognostic value and associations with clinical features, immune subtypes, stemness, tumor microenvironments, single-cell functional states, and drug sensitivity. HTGPCR expression differed between tumors and normal tissue, related to survival and immune checkpoint biology, and showed connections with stemness scores, TMB, MSI, and stromal/immune scores. Functional validation indicated HTR1D supports breast cancer growth and metastasis, suggesting therapeutic promise.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages21

Reading Time53 min

AccessFree to download

Abstract

Introduction

Background and rationale

Serotonin signaling and HTGPCR classification

Methods and analyses

Gene expression and prognostic evaluation

Clinical and immune-state associations

Tumor microenvironment and single-cell analysis

Drug sensitivity and validation

Article 5-Hydroxytryptamine G-Protein-Coupled Receptor Family Genes: Key Players in Cancer Prognosis, Immune Regulation, and Therapeutic Response Simeng Liu 1,2,†, Mingang He 1,2,†, Hefen Sun 1,2, Yi Wu 1,2 and Wei Jin 1,2, * Citation: Liu, S.; He, M.; Sun, H.; Wu, Y.; Jin, W. 5-Hydroxytryptamine G-Protein-Coupled Receptor Family Genes: Key Players in Cancer Prognosis, Immune Regulation, and Therapeutic Response. Genes 2024, 15, 1541. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)genes15121541 Academic Editor: Gael Roue Received: 31 October 2024 Revised: 23 November 2024 Accepted: 26 November 2024 Published: 28 November 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai 200032, China 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China * [Correspondence: jinwei@fudan.edu.cn](Correspondence: jinwei@fudan.edu.cn) † These authors contributed equally to this work. Abstract: Background: Firstly, 5-hydroxytryptamine G-protein-coupled receptors (HTGPCRs) are a family of 13 genes associated with cancer progression. Nevertheless, a comprehensive understanding of HTGPCRs in cancer remains largely lacking. Method: We tested the gene expression levels and prognostic values for the HTGPCRs in relation to pan-cancer. A subsequent analysis examined the relationships among HTGPCR expression and clinical characteristics, immune subtypes, stemness scores, tumor microenvironments (TMEs), single-cell analyses, and drug sensitivity. Result: A significant difference in HTGPCR expression was found between normal tissues and tumors. HTR1D/2C expressed higher levels in breast invasive carcinoma (BRCA), colon adenocarcinoma, and liver hepatocellular carcinoma. HTGPCR gene expression was correlated with prognosis in many cancers. HTR1D/2C were associated with poorer overall survival for head and neck squamous cell carcinoma. In addition, HTGPCR expression correlated significantly with the stemness scores of RNA and DNA, TMB, and MSI, as well as stromal and immune scores of pan-cancer patients. Additionally, the expression of HTR2A/2B/7 was correlated significantly with immune cells and immune checkpoint genes in a variety of cancers, such as BRCA, brain lower-grade glioma, and lung adenocarcinoma. Immune regulation and TME were both regulated by HTGPCRs. Using single-cell analysis, we found that the gene set of HTGPCRs correlated with many cancer-related functional states in retinoblastoma. Moreover, drug sensitivity and HTR4 were significantly correlated. Furthermore, we validated results in breast cancer and found knockdown of HTR1D inhibited breast cancer cell growth and metastasis. Conclusion: As prognostic indicators, HTGPCRs hold considerable promise and offer insights into the therapeutic targets for malignancy. Keywords: HTGPCR family genes; prognosis; pan-cancer; tumor microenvironment; therapeutic targets 1. Introduction As reported by the Global Cancer Statistics 2022, cancer continues to be a major worldwide health issue, with nearly 20 million new cancer diagnoses and approximately 9.7 million cancer-related deaths in 2022 [1,2] . The nervous system and cancer can interact with each other, a long-described phenomenon [3,4] . The roles of the central and peripheral nervous systems are closely linked to cancer, influencing tumor growth, vascular systems, immune responses, and the body’s capacity for resilience and self-repair [5] . Focusing on the interactions between the nervous system and cancer could become a cornerstone of cance

FAQs

What is the central research focus of this study?

To determine how 5-hydroxytryptamine G-protein-coupled receptor (HTGPCR) family genes relate to cancer prognosis, immune regulation, tumor microenvironments, and therapeutic response.

How do HTGPCR genes differ between normal tissues and tumors?

The study reports a significant difference in HTGPCR expression between normal tissues and tumor samples, with certain genes showing higher expression in specific cancer types.

What evidence links HTGPCRs to immune regulation and treatment response?

HTGPCR expression correlates with immune cell infiltration and immune checkpoint gene expression, associates with TMB and MSI, and single-cell analysis links HTGPCR gene sets to cancer-related functional states; drug sensitivity correlations and HTR1D knockdown support therapeutic relevance.

Sep 21, 2026

Uploaded by Theodora