Squamous Cell Carcinoma Antigen-encoding Genes SERPINB3/B4 as Potentially Useful Markers for the Stratification of HNSCC Tumours

Saidak, Zuzana; Morisse, Mony Chenda; Chatelain, Denis; Sauzay, Chloé; Houessinon, Aline; Guilain, Nelly; Soyez, Marion; Chauffert, Bruno; Dakpe, Stéphanie; Galmiche, Antoine

doi:10.21873/anticanres.12357

Cited by 6 publications

(5 citation statements)

References 27 publications

(36 reference statements)

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“…The ability to neutralize intracellular proteases and induce the UPR was suggested to contribute to the installation of a pro-inflammatory phenotype characterized by high expression of interleukin-6 (IL6) [76,77]. This link was specifically addressed in HNSCC by Saidak et al using transcriptomic data available from TCGA [78]. In HPV-negative HNSCC, a strong association was found between SERPINB3/B4 mRNA levels and the presence of a denser tumor immune infiltrate, an IFN-Gamma signature and the expression of the immune checkpoint regulator PD-L1 [78].…”

Section: Linking Specific Aspects Of Hnscc Physiology To the Uprmentioning

confidence: 99%

“…This link was specifically addressed in HNSCC by Saidak et al using transcriptomic data available from TCGA [78]. In HPV-negative HNSCC, a strong association was found between SERPINB3/B4 mRNA levels and the presence of a denser tumor immune infiltrate, an IFN-Gamma signature and the expression of the immune checkpoint regulator PD-L1 [78]. In this situation, the induction of a chronic UPR might be one important determinant of local tumor inflammation, with potential implications for carcinogenesis and the response to treatment.…”

Section: Linking Specific Aspects Of Hnscc Physiology To the Uprmentioning

confidence: 99%

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Impact and Relevance of the Unfolded Protein Response in HNSCC

Pluquet

Galmiche

2019

IJMS

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Head and neck squamous cell carcinomas (HNSCC) encompass a heterogeneous group of solid tumors that arise from the upper aerodigestive tract. The tumor cells face multiple challenges including an acute demand of protein synthesis often driven by oncogene activation, limited nutrient and oxygen supply and exposure to chemo/radiotherapy, which forces them to develop adaptive mechanisms such as the Unfolded Protein Response (UPR). It is now well documented that the UPR, a homeostatic mechanism, is induced at different stages of cancer progression in response to intrinsic (oncogenic activation) or extrinsic (microenvironment) perturbations. This review will discuss the role of the UPR in HNSCC as well as in the key processes that characterize the physiology of HNSCC. The role of the UPR in the clinical context of HNSCC will also be addressed.

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Section: Linking Specific Aspects Of Hnscc Physiology To the Uprmentioning

confidence: 99%

Section: Linking Specific Aspects Of Hnscc Physiology To the Uprmentioning

confidence: 99%

Impact and Relevance of the Unfolded Protein Response in HNSCC

Pluquet

Galmiche

2019

IJMS

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“…Although inhibitory T-cell receptor signaling was not investigated in this study, some suggest a potential connection between SERPINB3 and PD-L1 expression. In HPV-negative head and neck squamous cell carcinoma patients from TCGA database, high SERPINB3 expression corresponded to increased PD-L1 and PD-L2 (43). Similarly, genome-level and IHC showed upregulated PD-L1 in SERPINB3-high ovarian and esophageal tumors (44).…”

Section: Discussionmentioning

confidence: 99%

SCCA1/SERPINB3 promotes suppressive immune environment via STAT-dependent chemokine production, blunting the therapy-induced T cell responses

Markovina

Chen

Shi

et al. 2023

Preprint

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Radiotherapy is a commonly used cancer treatment; however, patients with high serum squamous cell carcinoma antigen (SCCA1/SERPINB3) are associated with resistance and poor prognosis. Despite being a strong clinical biomarker, the modulation of SERPINB3 in tumor immunity is poorly understood. We investigated the microenvironment of SERPINB3 high tumors through RNAseq of primary cervix tumors and found that SERPINB3 was positively correlated with CXCL1/8, S100A8/A9 and myeloid cell infiltration. Induction of SERPINB3 in vitro resulted in increased CXCL1/8 and S100A8/A9 production, and supernatants from SERPINB3-expressing cultures attracted monocytes and MDSCs. In murine tumors, the orthologue mSerpinB3a promoted MDSC, TAM, and M2 macrophage infiltration contributing to an immunosuppressive phenotype, which was further augmented upon radiation. Radiation-enhanced T cell response was muted in SERPINB3 tumors, whereas Treg expansion was observed. A STAT-dependent mechanism was implicated, whereby inhibiting STAT signaling with ruxolitinib abrogated suppressive chemokine production. Patients with elevated pre-treatment serum SCCA and high pSTAT3 had increased intratumoral CD11b+ myeloid cell compared to patients with low SCCA and pSTAT3 cohort that had overall improved cancer specific survival after radiotherapy. These findings provide a preclinical rationale for targeting STAT signaling in tumors with high SERPINB3 to counteract the immunosuppressive microenvironment and improve response to radiation.

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“…The squamous cell carcinoma antigen 2, encoded by the genes SERPINB3 and SERPINB4, has been shown to be involved in inflammatory conditions of the skin and respiratory diseases, such as chronic obstructive pulmonary disease and tuberculosis [ 58 ]. It has been used as a diagnostic marker for advanced squamous cell carcinoma in the head and neck [ 59 ]. Moreover, it has been found to induce Epithelial-Mesenchymal Transition (EMT) in mammalian epithelial cells, insinuating its role in tumor metastasis [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Biomarker Discovery for Meta-Classification of Melanoma Metastatic Progression Using Transfer Learning

Miñoza

Rico

Zamora

et al. 2022

Genes

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Melanoma is considered to be the most serious and aggressive type of skin cancer, and metastasis appears to be the most important factor in its prognosis. Herein, we developed a transfer learning-based biomarker discovery model that could aid in the diagnosis and prognosis of this disease. After applying it to the ensemble machine learning model, results revealed that the genes found were consistent with those found using other methodologies previously applied to the same TCGA (The Cancer Genome Atlas) data set. Further novel biomarkers were also found. Our ensemble model achieved an AUC of 0.9861, an accuracy of 91.05, and an F1 score of 90.60 using an independent validation data set. This study was able to identify potential genes for diagnostic classification (C7 and GRIK5) and diagnostic and prognostic biomarkers (S100A7, S100A7, KRT14, KRT17, KRT6B, KRTDAP, SERPINB4, TSHR, PVRL4, WFDC5, IL20RB) in melanoma. The results show the utility of a transfer learning approach for biomarker discovery in melanoma.

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Squamous Cell Carcinoma Antigen-encoding Genes SERPINB3/B4 as Potentially Useful Markers for the Stratification of HNSCC Tumours

Abstract: Abstract. Background

Cited by 6 publications

References 27 publications

Impact and Relevance of the Unfolded Protein Response in HNSCC

Impact and Relevance of the Unfolded Protein Response in HNSCC

SCCA1/SERPINB3 promotes suppressive immune environment via STAT-dependent chemokine production, blunting the therapy-induced T cell responses

Biomarker Discovery for Meta-Classification of Melanoma Metastatic Progression Using Transfer Learning

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