Multiomics data analyses to identify SLC25A17 as a novel biomarker to predict the prognosis and immune microenvironment in head and neck squamous cell carcinoma

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Abstract

Objective

This study aims to explore the predictive value of SLC25A17 in the prognosis and tumor microenvironment (TME) of patients with head and neck squamous cell carcinoma (HNSCC) and to provide ideas for individual clinical treatment.

Methods

A pancancer analysis of the differential expression of SLC25A17 among different tumors was first conducted via the TIMER 2.0 database. Subsequently, the expression of SLC25A17 and related clinical information of HNSCC patients were obtained from the TCGA database, and patients were divided into two groups according to the median value of SLC25A17 expression. K‒M survival analysis was conducted to compare the overall survival (OS) and progression-free survival (PFS) between the groups. The Wilcoxon test was used to compare the distribution of SLC25A17 in different clinical characteristics, and univariate Cox and multivariate Cox analyses were performed to analyze independent prognostic factors to establish a predictive nomogram. Calibration curves were generated to verify the reliability of predicting 1-year, 3-year and 5-year survival rates and another cohort (GSE65858) was used for external validation. Gene set enrichment analysis was conducted to compare the enriched pathways, and the immune microenvironment was assessed using the CIBERSORT and estimate packages. Furthermore, the expression levels of SLC25A17 in immune cells were also analyzed with single-cell RNA-seq via the TISCH. Moreover, the immunotherapeutic response and chemotherapy drug sensitivity were compared between the two groups to guide precise treatment. The TIDE database was applied to predict the possibility of immune escape in the TCGA-HNSC cohort.

Results

Compared with normal samples, the expression of SLC25A17 was much higher in HNSCC tumor samples. For patients with high SLC25A17 expression, the OS and PFS were shorter than those with low SLC25A17 expression, indicating a worse prognosis. The expression of SLC25A17 varied in different clinical features. Univariate Cox and multivariate COX analyses showed that SLC25A17, age, and lymph node metastasis are independent prognostic risk factors for HNSCC, and the survival prediction model based on these factors had reliable predictive value. Patients in the low-expression group exhibited more immune cell infiltration, higher TME scores, higher IPS scores and lower TIDE scores than those in the high-expression groups, suggesting better immunotherapeutic response with lower SLC25A17 expression. Moreover, patients in the high-expression group were more sensitive to chemotherapy.

Conclusions

SLC25A17 can effectively predict the prognosis of HNSCC patients and could be a precise individual-targeted indicator for the treatment of HNSCC patients.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12859-023-05399-6.

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Rebecca Siegel, Kimberly D Miller, Hannah Fuchs … (2022)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes. Incidence data (through 2018) were collected by the Surveillance, Epidemiology, and End Results program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2019) were collected by the National Center for Health Statistics. In 2022, 1,918,030 new cancer cases and 609,360 cancer deaths are projected to occur in the United States, including approximately 350 deaths per day from lung cancer, the leading cause of cancer death. Incidence during 2014 through 2018 continued a slow increase for female breast cancer (by 0.5% annually) and remained stable for prostate cancer, despite a 4% to 6% annual increase for advanced disease since 2011. Consequently, the proportion of prostate cancer diagnosed at a distant stage increased from 3.9% to 8.2% over the past decade. In contrast, lung cancer incidence continued to decline steeply for advanced disease while rates for localized-stage increased suddenly by 4.5% annually, contributing to gains both in the proportion of localized-stage diagnoses (from 17% in 2004 to 28% in 2018) and 3-year relative survival (from 21% to 31%). Mortality patterns reflect incidence trends, with declines accelerating for lung cancer, slowing for breast cancer, and stabilizing for prostate cancer. In summary, progress has stagnated for breast and prostate cancers but strengthened for lung cancer, coinciding with changes in medical practice related to cancer screening and/or treatment. More targeted cancer control interventions and investment in improved early detection and treatment would facilitate reductions in cancer mortality.

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A dynamic and mutualistic interaction between tumour cells and the surrounding stroma promotes the initiation, progression, metastasis and chemoresistance of solid tumours. Far less understood is the relationship between the stroma and tumour-infiltrating leukocytes; however, emerging evidence suggests that the stromal compartment can shape antitumour immunity and responsiveness to immunotherapy. Thus, there is growing interest in elucidating the immunomodulatory roles of the stroma that evolve within the tumour microenvironment. In this Review, we discuss the evidence that stromal determinants interact with leukocytes and influence antitumour immunity, with emphasis on the immunological attributes of stromal cells that may foster their protumorigenic function.

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Xu Lei, Yu Lei, Jin-Ke Li … (2019)

The immune cells within the tumor microenvironment (TME) play important roles in tumorigenesis. It has been known that these tumor associated immune cells may possess tumor-antagonizing or tumor-promoting functions. Although the tumor-antagonizing immune cells within TME tend to target and kill the cancer cells in the early stage of tumorigenesis, the cancer cells seems to eventually escape from immune surveillance and even inhibit the cytotoxic function of tumor-antagonizing immune cells through a variety of mechanisms. The immune evasion capability, as a new hallmark of cancer, accidently provides opportunities for new strategies of cancer therapy, namely harnessing the immune cells to battle the cancer cells. Recently, the administrations of immune checkpoint modulators (represented by anti-CTLA4 and anti-PD antibodies) and adoptive immune cells (represented by CAR-T) have exhibited unexpected antitumor effect in multiple types of cancer, bringing a new era for cancer therapy. Here, we review the biological functions of immune cells within TME and their roles in cancer immunotherapy, and discuss the perspectives of the basic studies for improving the effectiveness of the clinical use.

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Author and article information

Contributors

Juntao Huang: 798749265@qq.com

Yi Shen: tyzdhs@163.com

Journal

Journal ID (nlm-ta): BMC Bioinformatics

Journal ID (iso-abbrev): BMC Bioinformatics

Title: BMC Bioinformatics

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2105

Publication date (Electronic): 29 June 2023

Publication date PMC-release: 29 June 2023

Publication date Collection: 2023

Volume: 24

Electronic Location Identifier: 269

Affiliations

[1 ]GRID grid.203507.3, ISNI 0000 0000 8950 5267, Department of Otolaryngology Head and Neck Surgery, Ningbo Medical Center Lihuili Hospital, , The Affiliated Lihuili Hospital of Ningbo University, ; Ningbo, Zhejiang China

[2 ]GRID grid.203507.3, ISNI 0000 0000 8950 5267, School of Medicine, , Ningbo University, ; Ningbo, Zhejiang China

[3 ]GRID grid.459833.0, ISNI 0000 0004 1799 3336, Department of Otolaryngology Head and Neck Surgery, , Ningbo No.2 Hospital, ; Ningbo, China

Article

Publisher ID: 5399

DOI: 10.1186/s12859-023-05399-6

PMC ID: 10308725

PubMed ID: 37386359

SO-VID: 4e05e36d-4159-44cd-a7d3-8c65c0f7fb7e

License:

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