Co-expression Pattern of SLC Transporter Genes Associated with the Immune Landscape and Clinical Outcomes in Gastric Cancer

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2023 Nov 1

PMID 37909856

Authors

Yue Zhang

Zhihong Liu

Lingbo Li

Dongqiang Zeng

Huiying Sun

Jianhua Wu

Rui Zhou

Wangjun Liao

Affiliations

Soon will be listed here.

Abstract

Solute carrier (SLC) transporters play a dual role in the occurrence and progression of tumours by acting as both suppressors and promoters. However, the overall impact of SLC transcriptome signatures on the tumour microenvironment, biological behaviour and clinical stratification of gastric cancer has not been thoroughly investigated. Therefore, we comprehensively analysed the expression profiles of the SLC transporter family members to identify novel molecular subtypes in gastric cancer. We identified two distinct SLC subtypes, SLC-S1 and SLC-S2, using non-negative matrix factorization. These subtypes were markedly linked with the tumour microenvironment landscape, biological pathway activation and distinct clinical features of gastric cancer. Furthermore, a new scoring model, the SLC score, was developed to quantify the SLC subtypes. High SLC scores indicated a pattern of 'SLC-S2', characterized by stromal infiltration and activation, poor prognosis and insensitivity to chemotherapy and immunotherapy, but high sensitivity to imatinib. The SLC score could serve as a supplement to the Tumour Node Metastasis (TNM) staging system to guide personalized treatment strategies and predict prognosis for patients with gastric cancer.

Citing Articles

Computational Characterization of Membrane Proteins as Anticancer Targets: Current Challenges and Opportunities.

Gorostiola Gonzalez M, Rakers P, Jespers W, IJzerman A, Heitman L, van Westen G Int J Mol Sci. 2024; 25(7).

PMID: 38612509 PMC: 11011372. DOI: 10.3390/ijms25073698.

Co-expression pattern of SLC transporter genes associated with the immune landscape and clinical outcomes in gastric cancer.

Zhang Y, Liu Z, Li L, Zeng D, Sun H, Wu J J Cell Mol Med. 2023; 27(24):4181-4194.

PMID: 37909856 PMC: 10746955. DOI: 10.1111/jcmm.18003.

References

Zhao H, Tong Y, Pan S, Qiu Z, Liu P, Guo P . RBPMS2, as a novel biomarker for predicting lymph node metastasis, guides therapeutic regimens in gastric cancer. Hum Cell. 2022; 35(2):599-612. DOI: 10.1007/s13577-021-00667-0. View

Zhang J, Xu Y, Gao Y, Chen C, Zheng Z, Yun M . Retraction Note: Decreased expression of miR-939 contributes to chemoresistance and metastasis of gastric cancer via dysregulation of SLC34A2 and Raf/MEK/ERK pathway. Mol Cancer. 2022; 21(1):227. PMC: 9795626. DOI: 10.1186/s12943-022-01702-w. View

Chen M, Yang Y, Liu Y, Chen C . The Role of Chromosome Deletions in Human Cancers. Adv Exp Med Biol. 2018; 1044:135-148. DOI: 10.1007/978-981-13-0593-1_9. View

Liu X, Li T, Ma Z, Riederer B, Yuan D, Zhu J . SLC26A9 deficiency causes gastric intraepithelial neoplasia in mice and aggressive gastric cancer in humans. Cell Oncol (Dordr). 2022; 45(3):381-398. PMC: 9187568. DOI: 10.1007/s13402-022-00672-x. View

Polanski R, Hodgkinson C, Fusi A, Nonaka D, Priest L, Kelly P . Activity of the monocarboxylate transporter 1 inhibitor AZD3965 in small cell lung cancer. Clin Cancer Res. 2013; 20(4):926-937. PMC: 3929348. DOI: 10.1158/1078-0432.CCR-13-2270. View

Hugo W, Zaretsky J, Sun L, Song C, Moreno B, Hu-Lieskovan S . Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma. Cell. 2016; 165(1):35-44. PMC: 4808437. DOI: 10.1016/j.cell.2016.02.065. View

Brisam M, Rauthe S, Hartmann S, Linz C, Brands R, Kubler A . Expression of MAGE-A1-A12 subgroups in the invasive tumor front and tumor center in oral squamous cell carcinoma. Oncol Rep. 2016; 35(4):1979-86. DOI: 10.3892/or.2016.4600. View

El-Gebali S, Bentz S, Hediger M, Anderle P . Solute carriers (SLCs) in cancer. Mol Aspects Med. 2013; 34(2-3):719-34. DOI: 10.1016/j.mam.2012.12.007. View

Rask-Andersen M, Almen M, Schioth H . Trends in the exploitation of novel drug targets. Nat Rev Drug Discov. 2011; 10(8):579-90. DOI: 10.1038/nrd3478. View

10.

Hediger M, Clemencon B, Burrier R, Bruford E . The ABCs of membrane transporters in health and disease (SLC series): introduction. Mol Aspects Med. 2013; 34(2-3):95-107. PMC: 3853582. DOI: 10.1016/j.mam.2012.12.009. View

11.

Chia N, Tan P . Molecular classification of gastric cancer. Ann Oncol. 2016; 27(5):763-9. DOI: 10.1093/annonc/mdw040. View

12.

Wang W, Zou W . Amino Acids and Their Transporters in T Cell Immunity and Cancer Therapy. Mol Cell. 2020; 80(3):384-395. PMC: 7655528. DOI: 10.1016/j.molcel.2020.09.006. View

13.

Song W, Li D, Tao L, Luo Q, Chen L . Solute carrier transporters: the metabolic gatekeepers of immune cells. Acta Pharm Sin B. 2020; 10(1):61-78. PMC: 6977534. DOI: 10.1016/j.apsb.2019.12.006. View

14.

Zabarovsky E, Lerman M, Minna J . Tumor suppressor genes on chromosome 3p involved in the pathogenesis of lung and other cancers. Oncogene. 2002; 21(45):6915-35. DOI: 10.1038/sj.onc.1205835. View

15.

Jiang Y, Zhang Q, Hu Y, Li T, Yu J, Zhao L . ImmunoScore Signature: A Prognostic and Predictive Tool in Gastric Cancer. Ann Surg. 2016; 267(3):504-513. DOI: 10.1097/SLA.0000000000002116. View

16.

Schumann T, Konig J, Henke C, Willmes D, Bornstein S, Jordan J . Solute Carrier Transporters as Potential Targets for the Treatment of Metabolic Disease. Pharmacol Rev. 2019; 72(1):343-379. DOI: 10.1124/pr.118.015735. View

17.

Lawrence M, Stojanov P, Polak P, Kryukov G, Cibulskis K, Sivachenko A . Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013; 499(7457):214-218. PMC: 3919509. DOI: 10.1038/nature12213. View

18.

Kanai Y . Amino acid transporter LAT1 (SLC7A5) as a molecular target for cancer diagnosis and therapeutics. Pharmacol Ther. 2021; 230:107964. DOI: 10.1016/j.pharmthera.2021.107964. View

19.

Zhou R, Li L, Xi S, Zhang Y, Liu Z, Zeng D . Expression pattern of secretory-cell-related transcriptional signatures in colon adenocarcinomas defines tumor microenvironment characteristics and correlates with clinical outcomes. Mol Oncol. 2022; 17(3):499-517. PMC: 9980301. DOI: 10.1002/1878-0261.13338. View

20.

Zhang Y, Liu Z, Li L, Zeng D, Sun H, Wu J . Co-expression pattern of SLC transporter genes associated with the immune landscape and clinical outcomes in gastric cancer. J Cell Mol Med. 2023; 27(24):4181-4194. PMC: 10746955. DOI: 10.1111/jcmm.18003. View