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Open Access 01-12-2024 | Gastric Cancer | Research

SLITRK2 as a prognostic and immunological biomarker in gastric cancer

Authors: Huiqiong Zhu, Hailin Xiong, Xuli Guo, Haojie Liao, Shuyi Zhang

Published in: Discover Oncology | Issue 1/2024

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Abstract

Background

SLIT and NTRK-like protein 2 (SLITRK2) encodes a transmembrane protein that regulates neurite outgrowth. Some studies have demonstrated that SLITRK2 overexpressed in glioma. But the expression pattern, prognostic value and immunologic function of SLITRK2 in tumors remains unknown.

Methods

The expression pattern of SLITRK2 among pan-cancers was examined through the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). We analyzed the association between SLITRK2 expression level and tumor stage among pan-cancers. Kaplan–Meier survival analysis was utilized to investigate the prognostic relevance of SLITRK2 across 33 different types of cancers. Moreover, the correlations among SLITRK2 expression, immune cell infiltration, immunomodulatory related genes, tumor mutation burden (TMB), microsatellite instability (MSI) were evaluated. The relationship between SLITRK2 expression and crucial genes mutations was also illustrated. By using tissue microarray (TMA), the expression of SLITRK2 in 89 paired gastric cancer (GC) tissues was investigated.

Results

Our study indicated that SLITRK2 expression varied across cancers. Elevated SLITRK2 expression was positively related to advanced tumor stage, poor overall survival (OS) and reduced disease-free survival (DFS). Bioinformatic analyses underscore SLITRK2’s role in immune response, with its expression significantly tied to immune cell infiltration and marker expression. Based on TMA data, SLITRK2 expression level was positively associated with differentiation, lymph node metastasis, AJCC stage, TNM stage, and poor survival outcome in GC patients.

Conclusion

Our findings provided that SLITRK2 may function as a biomarker by regulating immune cell infiltration. In addition, we verified that high SLITRK2 expression was correlated with poor prognosis in GC.
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Literature
1.
Kumari EN. CA: a cancer journal for clinicians: a bibliometrics study. Libr Philos Pract. 2021; 1–12.
2.
Binnewies M, Roberts EW, Kersten K, Chan V, Fearon DF, Merad M, Coussens LM, Gabrilovich DI, Ostrand-Rosenberg S, Hedrick CC, Vonderheide RH, Pittet MJ, Jain RK, Zou W, Howcroft TK, Woodhouse EC, Weinberg RA, Krummel MF. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med. 2018;24:541–50.CrossRefPubMedPubMedCentral
3.
4.
Zhang H, Dai Z, Wu W, Wang Z, Zhang N, Zhang L, Zeng WJ, Liu Z, Cheng Q. Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer. J Exp Clin Cancer Res. 2021;40:184.CrossRefPubMedPubMedCentral
5.
Bagchi S, Yuan R, Engleman EG. Immune checkpoint inhibitors for the treatment of cancer: clinical impact and mechanisms of response and resistance. Annu Rev Pathol. 2021;16:223–49.CrossRefPubMed
6.
El Chehadeh S, Han KA, Kim D, Jang G, Bakhtiari S, Lim D, Kim HY, Kim J, Kim H, Wynn J, Chung WK, Vitiello G, Cutcutache I, Page M, Gecz J, Harper K, Han AR, Kim HM, Wessels M, Bayat A, Jaen AF, Selicorni A, Maitz S, de Brouwer APM, Silfhout AV, Armstrong M, Symonds J, Kury S, Isidor B, Cogne B, Nizon M, Feger C, Muller J, Torti E, Grange DK, Willems M, Kruer MC, Ko J, Piton A, Um JW. SLITRK2 variants associated with neurodevelopmental disorders impair excitatory synaptic function and cognition in mice. Nat Commun. 2022;13:4112.CrossRefPubMedPubMedCentral
7.
Katayama KI, Morimura N, Kobayashi K, Corbett D, Okamoto T, Ornthanalai VG, Matsunaga H, Fujita W, Matsumoto Y, Akagi T, Hashikawa T, Yamada K, Murphy NP, Nagao S, Aruga J. Slitrk2 deficiency causes hyperactivity with altered vestibular function and serotonergic dysregulation. iScience. 2022;25:104604.
8.
Li F, Zhang W, Wang M, Jia P. IL1RAP regulated by PRPRD promotes gliomas progression via inducing neuronal synapse development and neuron differentiation in vitro. Pathol Res Pract. 2020;216:153141.CrossRefPubMed
9.
Wang Y, Wang K, Chen Y, Zhou J, Liang Y, Yang X, Li X, Cao Y, Wang D, Luo L, Li B, Li D, Wang L, Liang Z, Gao C, Wang Q, Lv Q, Li Z, Shi Y, Niu H. Mutational landscape of penile squamous cell carcinoma in a Chinese population. Int J Cancer. 2019;145:1280–9.CrossRefPubMed
10.
Tang Z, Kang B, Li C, Chen T, Zhang Z. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019;47:W556–60.CrossRefPubMedPubMedCentral
11.
Choucair K, Morand S, Stanbery L, Edelman G, Dworkin L, Nemunaitis J. TMB: a promising immune-response biomarker, and potential spearhead in advancing targeted therapy trials. Cancer Gene Ther. 2020;27:841–53.CrossRefPubMed
12.
Steuer CE, Ramalingam SS. Tumor mutation burden: leading immunotherapy to the era of precision medicine? J Clin Oncol. 2018;36:631–2.CrossRefPubMed
13.
Bonneville R, Krook MA, Chen HZ, Smith A, Samorodnitsky E, Wing MR, Reeser JW, Roychowdhury S. Detection of microsatellite instability biomarkers via next-generation sequencing. Methods Mol Biol. 2020;2055:119–32.CrossRefPubMedPubMedCentral
14.
Ratovomanana T, Nicolle R, Cohen R, Diehl A, Siret A, Letourneur Q, Buhard O, Perrier A, Guillerm E, Coulet F, Cervera P, Benusiglio P, Labreche K, Colle R, Collura A, Despras E, Le Rouzic P, Renaud F, Cros J, Alentorn A, Touat M, Ayadi M, Bourgoin P, Prunier C, Tournigand C, Fouchardiere C, Tougeron D, Jonchere V, Bennouna J, de Reynies A, Flejou JF, Svrcek M, Andre T, Duval A. Prediction of response to immune checkpoint blockade in patients with metastatic colorectal cancer with microsatellite instability. Ann Oncol. 2023;34:703–13.CrossRefPubMed
15.
Nagy A, Gyorffy B. muTarget: a platform linking gene expression changes and mutation status in solid tumors. Int J Cancer. 2021;148:502–11.CrossRefPubMed
16.
17.
Singh AK, McGuirk JP. CAR T cells: continuation in a revolution of immunotherapy. Lancet Oncol. 2020;21:e168–78.CrossRefPubMed
18.
19.
Walk EE, Yohe SL, Beckman A, Schade A, Zutter MM, Pfeifer J, Berry AB, College of American Pathologists Personalized Health Care Committee. The cancer immunotherapy biomarker testing landscape. Arch Pathol Lab Med. 2020; 144:706–24.
20.
Hinshaw DC, Shevde LA. The tumor microenvironment innately modulates cancer progression. Can Res. 2019;79:4557–66.CrossRef
21.
Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell. 2012;21:309–22.CrossRefPubMed
22.
Klemm F, Joyce JA. Microenvironmental regulation of therapeutic response in cancer. Trends Cell Biol. 2015;25:198–213.CrossRefPubMed
23.
24.
Zhang Y, Zhang Z. The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell Mol Immunol. 2020;17:807–21.CrossRefPubMedPubMedCentral
25.
Zhang J, Endres S, Kobold S. Enhancing tumor T cell infiltration to enable cancer immunotherapy. Immunotherapy. 2019;11:201–13.CrossRefPubMed
26.
Chen Y, Jia K, Sun Y, Zhang C, Li Y, Zhang L, Chen Z, Zhang J, Hu Y, Yuan J, Zhao X, Li Y, Gong J, Dong B, Zhang X, Li J, Shen L. Predicting response to immunotherapy in gastric cancer via multi-dimensional analyses of the tumour immune microenvironment. Nat Commun. 2022;13:4851.CrossRefPubMedPubMedCentral
27.
Fancello L, Gandini S, Pelicci PG, Mazzarella L. Tumor mutational burden quantification from targeted gene panels: major advancements and challenges. J Immunother Cancer. 2019;7:183.CrossRefPubMedPubMedCentral
28.
Samstein RM, Lee CH, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, Barron DA, Zehir A, Jordan EJ, Omuro A, Kaley TJ, Kendall SM, Motzer RJ, Hakimi AA, Voss MH, Russo P, Rosenberg J, Iyer G, Bochner BH, Bajorin DF, Al-Ahmadie HA, Chaft JE, Rudin CM, Riely GJ, Baxi S, Ho AL, Wong RJ, Pfister DG, Wolchok JD, Barker CA, Gutin PH, Brennan CW, Tabar V, Mellinghoff IK, DeAngelis LM, Ariyan CE, Lee N, Tap WD, Gounder MM, D’Angelo SP, Saltz L, Stadler ZK, Scher HI, Baselga J, Razavi P, Klebanoff CA, Yaeger R, Segal NH, Ku GY, DeMatteo RP, Ladanyi M, Rizvi NA, Berger MF, Riaz N, Solit DB, Chan TA, Morris LGT. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 2019;51:202–6.CrossRefPubMedPubMedCentral
29.
McNamara MG, Jacobs T, Lamarca A, Hubner RA, Valle JW, Amir E. Impact of high tumor mutational burden in solid tumors and challenges for biomarker application. Cancer Treat Rev. 2020;89:102084.CrossRefPubMed
30.
31.
Sun BL. Current microsatellite instability testing in management of colorectal cancer. Clin Colorectal Cancer. 2021;20:e12–20.CrossRefPubMed
32.
Yamamoto H, Watanabe Y, Maehata T, Imai K, Itoh F. Microsatellite instability in cancer: a novel landscape for diagnostic and therapeutic approach. Arch Toxicol. 2020;94:3349–57.CrossRefPubMed
33.
Dzunic M, Andjelkovic-Apostolovic M, Vrbic S, Pejcic I, Petkovic I, Cvetanovic A, Dinic S. Survival of patients with liver metastases from colorectal cancer treated with bevacizumab and FOLFOX4. J BUON. 2020;25:212–9.
Metadata
Title
SLITRK2 as a prognostic and immunological biomarker in gastric cancer
Authors
Huiqiong Zhu
Hailin Xiong
Xuli Guo
Haojie Liao
Shuyi Zhang
Publication date
01-12-2024
Publisher
Springer US
Published in
Discover Oncology / Issue 1/2024
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI
https://doi.org/10.1007/s12672-024-01534-8

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