An Update on S100A16 in Human Cancer

Basnet, Suyog; Vallenari, Evan Michael; Maharjan, Urusha; Sharma, Sunita; Schreurs, Olav; Sapkota, Dipak

doi:10.3390/biom13071070

Cited by 12 publications

(7 citation statements)

References 40 publications

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“…S100A16, a calcium-binding protein, is widely expressed in tumor tissues, suggesting its potential involvement in malignant transformation or tumorigenesis. Speci cally, S100A16 overexpression has been observed in bladder, lung, thyroid, pancreatic, glioma, and ovarian tumors [12,20]. Functionally, S100A16 is involved in various aspects of tumorigenesis, including cell proliferation, differentiation, migration, invasion, and epithelial-mesenchymal transition.…”

Section: Discussionmentioning

confidence: 99%

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Validating S100A16 as a prognostic and immunological biomarker in pan-cancer and lung adenocarcinoma through integrated Single-cell Sequencing Analysis

Shi,

Yu,

Shang

et al. 2024

Preprint

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Background S100A16 belongs to the S100 protein family, exhibiting different expression levels across several human tumors. S100A16 upregulation in many malignancies suggests its potential role in malignant transformation. However, the specific involvement of S100A16 in lung adenocarcinoma (LUAD) remains unclear. Methods This study utilized RNA sequencing and protein expression data from the Cancer Genome Atlas (TCGA) and the Human Protein Atlas (THPA) databases to scrutinize the expression of S100A16 and its associations with patients’ prognosis, clinicopathological characteristics, tumor microenvironment (TME), immune cell infiltration, expression of immune checkpoint genes, and relevant signaling pathways in LUAD. Employing ESTIMATE and CIBERSORT algorithms alongside Gene Set Enrichment Analysis (GSEA), we investigated the underlying mechanisms by which LUAD is involved in the TME. Additionally, we used single-cell sequencing to measure the role of S100A16 at the cellular level and dissect the effect on treatment response in LUAD. Results S100A16 was highly expressed in LUAD. As an independent prognostic marker, S100A16 expression was correlated with adverse outcomes. Its expression levels were positively correlated with the clinical TN stage and LUAD grade. GO and KEGG analyses revealed the predominance of molecules positively associated with S100A16 expression in LUAD, concentrating on pathways related to cellular signaling, motility, morphology, and cell interactions. The high S100A16 group showed a significantly higher TME score compared with the low S100A16 expression group. Immune cells, including M1 macrophages, memory B cells, activated NK cells, plasma cells, and naive B cells, were positively associated with S100A16 expression in LUAD. Furthermore, a positive correlation was observed between S100A16 and the expression of most immune checkpoint genes. Patients with high S100A16 expression demonstrated lower IC50 values for drugs such as 5-fluorouracil, bortezomib, cisplatin, cytarabine, docetaxel, doxorubicin, etoposide, and vinorelbine, suggesting that S100A16 overexpression increased sensitivity to these treatments in LUAD. This study provides novel insights into the role of S100A16 in LUAD and associated signaling pathways. Conclusions S100A16 is an independent prognostic marker in LUAD, intricately linked to the TME, immune cell infiltration, immune checkpoint expression, and response to treatment. This study underscores the potential of S100A16 as a prognostic marker in LUAD, advancing cancer treatment.

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Section: Discussionmentioning

confidence: 99%

“…Besides, previous studies assessed the potential prognostic signi cance of S100A16 in various cancer types [12]. Interestingly, S100A16 has been proposed as a potentially useful prognostic marker for evaluating the effectiveness of adjuvant chemotherapy based on platinum in patients who underwent surgical resection of lung cancer [13].…”

Section: Introductionmentioning

confidence: 99%

Validating S100A16 as a prognostic and immunological biomarker in pan-cancer and lung adenocarcinoma through integrated Single-cell Sequencing Analysis

Shi,

Yu,

Shang

et al. 2024

Preprint

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“…These genes serve an important biological role in the occurrence and development of tumors. Among these genes, S100A16 is highly conserved in mammals ( 32 ), and its high expression is linked with tumor cell growth and EMT ( 33 ). S100A16 is a prognostic marker for various tumors, including LUAD and colorectal cancer ( 34 , 35 ).…”

Section: Discussionmentioning

confidence: 99%

Construction of an immune-related gene prognostic model with experimental validation and analysis of immune cell infiltration in lung adenocarcinoma

Yang,

Tang,

et al. 2024

Oncol Lett

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There is a correlation between tumors and immunity with the degree of immune cell infiltration in tumors being closely related to tumor growth and progression. Therefore, the present study identified immune-related prognostic genes and evaluated the immune infiltration level in lung adenocarcinoma (LUAD). This study performed Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and Gene Set Enrichment Analysis (GSEA) enrichment analyses on differential immune-associated genes. A risk model was created and validated using six immune-related prognostic genes. Reverse transcription-quantitative PCR was used to assess the prognostic gene expression in non-small cell lung cancer cells. Immune cell infiltration in LUAD was analyzed using the CIBERSORT method. Single sample GSEA was used to compare Tumor Immune Dysfunction and Exclusion (TIDE) scores between high and low-risk groups and to assess the activation of thirteen immune-related pathways. Multifactor Cox proportional hazards model analysis identified six prognostic risk genes ( S100A16, FURIN, FGF2, LGR4, TNFRSF11A and VIPR1 ) to construct a risk model. The survival and receiver operating characteristic curves indicated that patients with higher risk scores had lower overall survival rates. The expression levels of prognostic genes S100A16, FURIN, LGR4, TNFRSF11A and VIPR1 were significantly increased in LUAD. B cells naive, plasma cells, T cells CD4 memory activated, T cells follicular helper, T cells regulatory, NK cells activated, macrophages M1, macrophages M2, and Dendritic cells resting cells showed elevated expression in LUAD. The prognostic genes were differentially associated with individual immune cells. Immune-related function scores, such as those for antigen presenting cell (APC) co-stimulation, APC co-inhibition, check-point, Cytolytic-activity, chemokine receptor, parainflammation, major histocompatibility complex-class-I, type-I–IFN-reponse and T-cell-co-inhibition, were higher in the high-risk group compared with the low-risk group. Furthermore, the TIDE score of the high-risk group was significantly lower than the low-risk group. This immune-related gene prognostic model has the potential to predict the prognosis of LUAD patients, supporting the development of a personalized clinical diagnosis and treatment plan.

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“…Analyses based on BC cell lines have shown that Snail, the EMT-related transcription factor, regulates S100A16 [25]. The knockdown of S100A16 was shown to reduce the expression of N-cadherin, vimentin, and slug and increase the expression of E-cadherin in BC cells [10,26]. S100A16 may directly or indirectly act to EMT associated marker and induce EMT.…”

Section: Discussionmentioning

confidence: 99%

Expression of S100A16 Is Associated with Biological Aggressiveness and Poor Prognosis in Patients with Bladder Cancer Who Underwent Radical Cystectomy

Katsumata,

Matsumoto,

Yanagita

et al. 2023

IJMS

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S100 calcium binding protein A16 (S100A16) is expressed in various cancers; however, there are few reports on S100A16 in bladder cancer (BC). We retrospectively investigated clinical data including clinicopathological features in 121 patients with BC who underwent radical cystectomy (RC). Immunohistochemical staining was performed to evaluate S100A16 expression in archived specimens. Cases with >5% expression and more than moderate staining intensity on cancer cells were considered positive. S100A16 expression was observed in 54 patients (44.6%). Univariate analysis showed that S100A16 expression was significantly associated with age, pT stage, recurrence, and cancer-specific death. Kaplan–Meier analyses showed that patients with S100A16 expression had shorter overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) than those without S100A16 expression. In multivariate analysis, pT stage was an independent prognostic factor for OS and lymph node metastasis for CSS and RFS. S100A16 expression may be a biomarker of a biologically aggressive phenotype and poor prognosis in patients with BC who underwent RC. The PI3k/Akt signaling pathway is probably associated with S100A16 and may be a therapeutic target.

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An Update on S100A16 in Human Cancer

Cited by 12 publications

References 40 publications

Validating S100A16 as a prognostic and immunological biomarker in pan-cancer and lung adenocarcinoma through integrated Single-cell Sequencing Analysis

Validating S100A16 as a prognostic and immunological biomarker in pan-cancer and lung adenocarcinoma through integrated Single-cell Sequencing Analysis

Construction of an immune-related gene prognostic model with experimental validation and analysis of immune cell infiltration in lung adenocarcinoma

Expression of S100A16 Is Associated with Biological Aggressiveness and Poor Prognosis in Patients with Bladder Cancer Who Underwent Radical Cystectomy

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