Single-cell transcriptomes underscore genetically distinct tumor characteristics and microenvironment for hereditary kidney cancers

Jikuya, Ryosuke; Murakami, K.; Nishiyama, Akira; Kato, Ikuo; Furuya, Mitsuko; Nakabayashi, Jun; Ramilowski, Jordan A.; Hamanoue, Haruka; Maejima, Kazuhiro; Fujita, Masashi; Mitome, Taku; Ohtake, Shinji; Noguchi, Go; Kawaura, Sachi; Odaka, Hisakazu; Kawahara, Takashi; Komeya, Mitsuru; Shinoki, Risa; Ueno, Daiki; Ito, Hiroki; Ito, Yusuke; Muraoka, Kentaro; Hayashi, Narihiko; Kondo, Keiichi; Nakaigawa, Noboru; Hatano, Koji; M, Baba; Suda, Toshio; Kodama, Tatsuhiko; Fujii, Satoshi; Makiyama, Kazuhide; Yao, Masahiro; Shuch, Brian; Schmidt, Laura S.; Linehan, W. Marston; Nakagawa, Hidewaki; Tamura, Tomohide; Hasumi, Hisashi

doi:10.1016/j.isci.2022.104463

Cited by 4 publications

(4 citation statements)

References 51 publications

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“…9,10 Various single-cell data support that the imbalanced proportion of immune cells is an important characteristic of tumorigenesis. 11,12 It is reported that the polarization of M2 macrophage is important for the progression of RCC. 13 However, the reasons driving this phenomenon are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

“…In recent years, lots of studies show that tumor immune microenvironment is associated with tumor generation and development 9,10 . Various single‐cell data support that the imbalanced proportion of immune cells is an important characteristic of tumorigenesis 11,12 . It is reported that the polarization of M2 macrophage is important for the progression of RCC 13 .…”

Section: Introductionmentioning

confidence: 99%

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Gene LY96 is an M2 macrophage‐related biomarker and is associated with immunosuppression in renal cell carcinoma

Li,

Meng,

et al. 2023

MedComm – Oncology

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Lymphocyte Antigen 96 (LY96) was identified as an oncogene in several tumors. However, its role in renal cancer has not been explored. In the study, LY96 is identified abnormally expressed using several public kidney cancer sequencing data. The expression level of LY96 is validated using paired clinical samples. Survival analyses and ROC curves are used to examine its prognostic and diagnostic value. Gene sets enrichment analyses (GSEA) show LY96 might influence immune processes. Then immune infiltration analyses results suggest that LY96 is positively correlated with M2 macrophages infiltration in RCC. Single‐cell data are used to verify its association with macrophages. Moreover, LY96 is positively with various immune scores and might affect the efficacy of immunotherapy. Drug screening results show LY96 might be the target of vemurafenib and etoposide. Further experiments confirm the spatial co‐localization of LY96 and M2, and knocking down LY96 can inhibit M2 polarization. Cell viability experiments indicate that knocking down LY96 would result in a decrease in the resistance of M2 macrophages to etoposide. The study shows LY96 could act as an unfavorable biomarker for RCC and possibly contribute to cancer progression by promoting the infiltration of M2 macrophage. LY96 could be a novel therapeutic target for RCC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Gene LY96 is an M2 macrophage‐related biomarker and is associated with immunosuppression in renal cell carcinoma

Li,

Meng,

et al. 2023

MedComm – Oncology

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“…Though molecular characterization has been recently attempted in sporadic HOCT and limited cases of syndromic HOT, no candidate biomarkers were nominated or confirmed in clinical samples. 5,8 In our recent single-cell study of renal cell cancers (RCCs), we performed integrative analysis of next-generation RNA sequencing (RNA-seq) and singlecell sequencing data, identified cell of origin and nominated candidate biomarkers for various renal tumor subtypes, including chRCC and HOT. 9 We characterized the expression pattern of chRCC biomarkers, FOXI1, RHCG, and LINC01187, in a large cohort of RCC samples and confirmed these genes as lineage specific for intercalated cells (ICs) of distal tubules.…”

mentioning

confidence: 99%

“…This in turn helps identify candidate biomarkers to assist accurate diagnosis of related oncocytic neoplasms; such technologies also impart an enhanced insight into tumorogenesis in BHD patients, enable a cell of origin determination and help nominate diagnostic and prognostic biomarkers for renal tumors. Though molecular characterization has been recently attempted in sporadic HOCT and limited cases of syndromic HOT, no candidate biomarkers were nominated or confirmed in clinical samples 5,8 . In our recent single-cell study of renal cell cancers (RCCs), we performed integrative analysis of next-generation RNA sequencing (RNA-seq) and single-cell sequencing data, identified cell of origin and nominated candidate biomarkers for various renal tumor subtypes, including chRCC and HOT 9 .…”

mentioning

confidence: 99%

Hybrid Oncocytic Tumors (HOTs) in Birt-Hogg-Dubé Syndrome Patients—A Tale of Two Cities

Wang,

Mannan,

Zhang

et al. 2023

American Journal of Surgical Pathology

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Birt-Hogg-Dubé (BHD) syndrome is associated with an increased risk of multifocal renal tumors, including hybrid oncocytic tumor (HOT) and chromophobe renal cell carcinoma (chRCC). HOT exhibits heterogenous histologic features overlapping with chRCC and benign renal oncocytoma, posing challenges in diagnosis of HOT and renal tumor entities resembling HOT. In this study, we performed integrative analysis of bulk and single-cell RNA sequencing data from renal tumors and normal kidney tissues, and nominated candidate biomarkers of HOT, L1CAM, and LINC01187, which are also lineage-specific markers labeling the principal cell and intercalated cell lineages of the distal nephron, respectively. Our findings indicate the principal cell lineage marker L1CAM and intercalated cell lineage marker LINC01187 to be expressed mutually exclusively in a unique checkered pattern in BHD-associated HOTs, and these 2 lineage markers collectively capture the 2 distinct tumor epithelial populations seen to co-exist morphologically in HOTs. We further confirmed that the unique checkered expression pattern of L1CAM and LINC01187 distinguished HOT from chRCC, renal oncocytoma, and other major and rare renal cell carcinoma subtypes. We also characterized the histopathologic features and immunophenotypic features of oncocytosis in the background kidney of patients with BHD, as well as the intertumor and intratumor heterogeneity seen within HOT. We suggest that L1CAM and LINC01187 can serve as stand-alone diagnostic markers or as a panel for the diagnosis of HOT. These lineage markers will inform future studies on the evolution and interaction between the 2 transcriptionally distinct tumor epithelial populations in such tumors.

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Comparative analyses define differences between BHD-associated renal tumour and sporadic chromophobe renal cell carcinoma

Jikuya¹,

Johnson²,

Maejima³

et al. 2023

eBioMedicine

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Single-cell transcriptomes underscore genetically distinct tumor characteristics and microenvironment for hereditary kidney cancers

Cited by 4 publications

References 51 publications

Gene LY96 is an M2 macrophage‐related biomarker and is associated with immunosuppression in renal cell carcinoma

Gene LY96 is an M2 macrophage‐related biomarker and is associated with immunosuppression in renal cell carcinoma

Hybrid Oncocytic Tumors (HOTs) in Birt-Hogg-Dubé Syndrome Patients—A Tale of Two Cities

Comparative analyses define differences between BHD-associated renal tumour and sporadic chromophobe renal cell carcinoma

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