Clinical Significance and Expression of SLC35F6 in Bladder Urothelial Carcinoma

Overview

Journal Diagn Pathol

Publisher Biomed Central

Specialty Pathology

Date 2024 Nov 23

PMID 39578844

Authors

Jinling Zhang

Siqi Liu

Meng Wu

Wenyu Shi

Yihong Cai

Affiliations

Soon will be listed here.

Abstract

Background: SLC35F6 negatively regulates outer mitochondrial membrane permeability and positively regulates apoptotic signaling pathways and cell population proliferation. The biological function of SLC35F6 in bladder cancer (BC) remains inadequately established. This study evaluates the expression and clinical significance of SLC35F6 in BC, assesses its prognostic value and explores its relationship with key immune-related molecules in the tumor microenvironment.

Methods: Combining bioinformatics tools and immunohistochemistry (IHC) analysis, the expression of SLC35F6 was analyzed through IHC in the tissues of 145 BC patients treated at the Affiliated Hospital of Nantong University from 2004 to 2009. The relationship between SLC35F6 expression levels and significant clinicopathological factors was examined using the chi-square test. Prognostic values were analyzed using the COX regression model and the Kaplan-Meier survival curve. Analysis of the receiver operating characteristic curve was conducted to assess the predictive performance of SLC35F6 in BC patients.

Results: The expression levels of both SLC35F6 mRNA and protein were elevated in BC tissue relative to benign tissue. Kaplan-Meier analysis indicated that patients exhibiting elevated SLC35F6 protein expression had a worse prognosis. Multivariate Cox regression analysis confirmed that SLC35F6, TNM stage and grade are independent risk factors for bladder cancer. SLC35F6, when analyzed alongside clinical pathological factors, enhances the accuracy of survival predictions for Bladder Urothelial Carcinoma (BLCA) patients.

Conclusion: SLC35F6 is upregulated in BC patients compared to normal individuals and is linked to a worse prognosis. SLC35F6 analyzed alongside clinical pathological factors can enhance the accuracy of survival predictions for BLCA patients, suggesting its potential value as a prognostic and predictive biomarker.

References

Cheng T, Xu M, Zhang H, Lu B, Zhang X, Wang Z . KLHDC8A Expression in Association with Macrophage Infiltration and Oxidative Stress Predicts Unfavorable Prognosis for Glioma. Oxid Med Cell Longev. 2022; 2022:2694377. PMC: 9527113. DOI: 10.1155/2022/2694377. View

Sharma P, Retz M, Siefker-Radtke A, Baron A, Necchi A, Bedke J . Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017; 18(3):312-322. DOI: 10.1016/S1470-2045(17)30065-7. View

Bejarano L, Jordao M, Joyce J . Therapeutic Targeting of the Tumor Microenvironment. Cancer Discov. 2021; 11(4):933-959. DOI: 10.1158/2159-8290.CD-20-1808. View

Nakamura T, Furukawa Y, Nakagawa H, Tsunoda T, Ohigashi H, Murata K . Genome-wide cDNA microarray analysis of gene expression profiles in pancreatic cancers using populations of tumor cells and normal ductal epithelial cells selected for purity by laser microdissection. Oncogene. 2004; 23(13):2385-400. DOI: 10.1038/sj.onc.1207392. View

Xu N, Yao Z, Shang G, Ye D, Wang H, Zhang H . Integrated proteogenomic characterization of urothelial carcinoma of the bladder. J Hematol Oncol. 2022; 15(1):76. PMC: 9164575. DOI: 10.1186/s13045-022-01291-7. View

Patel V, Oh W, Galsky M . Treatment of muscle-invasive and advanced bladder cancer in 2020. CA Cancer J Clin. 2020; 70(5):404-423. DOI: 10.3322/caac.21631. View

Kashiwaya K, Hosokawa M, Eguchi H, Ohigashi H, Ishikawa O, Shinomura Y . Identification of C2orf18, termed ANT2BP (ANT2-binding protein), as one of the key molecules involved in pancreatic carcinogenesis. Cancer Sci. 2009; 100(3):457-64. PMC: 11158434. DOI: 10.1111/j.1349-7006.2008.01058.x. View

Shin A, Giancotti F, Rustgi A . Metastatic colorectal cancer: mechanisms and emerging therapeutics. Trends Pharmacol Sci. 2023; 44(4):222-236. PMC: 10365888. DOI: 10.1016/j.tips.2023.01.003. View

Patel S, Kurzrock R . PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy. Mol Cancer Ther. 2015; 14(4):847-56. DOI: 10.1158/1535-7163.MCT-14-0983. View

10.

Pizzagalli M, Bensimon A, Superti-Furga G . A guide to plasma membrane solute carrier proteins. FEBS J. 2020; 288(9):2784-2835. PMC: 8246967. DOI: 10.1111/febs.15531. View

11.

Lesseur C, Diergaarde B, Olshan A, Wunsch-Filho V, Ness A, Liu G . Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer. Nat Genet. 2016; 48(12):1544-1550. PMC: 5131845. DOI: 10.1038/ng.3685. View

12.

Flierl A, Schriner S, Hancock S, Coskun P, Wallace D . The mitochondrial adenine nucleotide transporters in myogenesis. Free Radic Biol Med. 2022; 188:312-327. DOI: 10.1016/j.freeradbiomed.2022.05.022. View

13.

Rosenbrock H, Desch M, Wunderlich G . Development of the novel GlyT1 inhibitor, iclepertin (BI 425809), for the treatment of cognitive impairment associated with schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2023; 273(7):1557-1566. PMC: 10465677. DOI: 10.1007/s00406-023-01576-z. View

14.

Pare L, Pascual T, Segui E, Teixido C, Gonzalez-Cao M, Galvan P . Association between PD1 mRNA and response to anti-PD1 monotherapy across multiple cancer types. Ann Oncol. 2018; 29(10):2121-2128. DOI: 10.1093/annonc/mdy335. View

15.

Hatogai K, Sweis R . The Tumor Microenvironment of Bladder Cancer. Adv Exp Med Biol. 2021; 1296:275-290. PMC: 8345230. DOI: 10.1007/978-3-030-59038-3_17. View

16.

Liu S, Chen X, Lin T . Emerging strategies for the improvement of chemotherapy in bladder cancer: Current knowledge and future perspectives. J Adv Res. 2022; 39:187-202. PMC: 9263750. DOI: 10.1016/j.jare.2021.11.010. View

17.

Liu F, Liu W, Sanin D, Jia G, Tian M, Wang H . Heterogeneity of exhausted T cells in the tumor microenvironment is linked to patient survival following resection in hepatocellular carcinoma. Oncoimmunology. 2020; 9(1):1746573. PMC: 7219269. DOI: 10.1080/2162402X.2020.1746573. View

18.

Cesar-Razquin A, Snijder B, Frappier-Brinton T, Isserlin R, Gyimesi G, Bai X . A Call for Systematic Research on Solute Carriers. Cell. 2015; 162(3):478-87. DOI: 10.1016/j.cell.2015.07.022. View

19.

Cerhan J, Berndt S, Vijai J, Ghesquieres H, McKay J, Wang S . Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma. Nat Genet. 2014; 46(11):1233-8. PMC: 4213349. DOI: 10.1038/ng.3105. View

20.

Wolacewicz M, Hrynkiewicz R, Grywalska E, Suchojad T, Leksowski T, Rolinski J . Immunotherapy in Bladder Cancer: Current Methods and Future Perspectives. Cancers (Basel). 2020; 12(5). PMC: 7281703. DOI: 10.3390/cancers12051181. View