A novel immune prognostic index for stratification of high-risk patients with early breast cancer

Lee, Hannah; Kwon, Mi; Koo, Bon Wook; Park, Hee Geon; Han, Jinil; Shin, Young Kee

doi:10.1038/s41598-020-80274-5

Cited by 5 publications

(5 citation statements)

References 40 publications

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“…Most of these genes had already been reported to be associated with various oncogenic processes, such as JUNB regulating TGFß signaling, invasion, and metastasis [46,47]. PTTG2 has been implicated in glioblastoma tumorigenesis, as well as in head and neck squamous cell carcinoma [36, 48], UTS2 has been reported to possess prognostic value in colorectal and breast cancers [49,50], TRAT1 in early breast cancer prognosis [51] and DUSP1 in sarcoma progression [52]. Of the 32 identi ed genes, nine were found to be associated with basal-like tumors.…”

Section: Discussionmentioning

confidence: 99%

Minimally invasive determination of PDAC subtype and therapy-induced subtype switch by means of circulating cell-free RNA

Lueong,

Metzenmacher,

Trajkovic-Arsic

et al. 2024

Preprint

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Background Pancreatic ductal adenocarcinoma (PDAC) comprises two clinically relevant subtypes. Currently, determining the tumor subtype relies on tissue biopsies. Unfortunately, these biopsies are spatially biased, highly invasive, difficult to obtain, and unsuitable for monitoring tumor dynamics. Methods We employed whole transcriptome sequencing (WTS) on circulating cell-free (cf) RNA in plasma samples from patients with well-characterized tumor subtypes. Additionally, quantitative protein mass spectrometry was utilized to identify minimally invasive markers for tumor subtypes. We validated our findings using independent liquid and tissue samples from large clinical trials and investigated treatment-induced subtype dynamics and responses. Results An exploratory analysis of 10 patients (four basal-like and six classical) was conducted using whole transcriptome sequencing (WTS). Following differential transcript abundance analysis and integration with expression data from tumor and non-tumor samples (N > 200), we identified 32 protein-coding subtype-specific cfRNA-defined transcripts. The subtype specificity of these transcripts was validated in two independent tissue cohorts comprising 195 and 250 cases, respectively. Three disease-relevant cfRNA-defined subtype markers (DEGS1, KDELC1, and RPL23AP7) consistently associated with basal-like tumors across all cohorts and were validated using machine learning. Further analysis of these markers using RT-ddPCR in over 160 patient sera and 24 samples from healthy donors revealed their predictive and prognostic value, as well as subtype specificity and therapy-induced dynamics. In both tumor and liquid biopsies, the overexpression of these markers was associated with poor overall and progression-free survival. Moreover, elevated tissue/liquid levels of the identified markers were linked to a poor response to systemic therapy and rapid disease recurrence in resected patients. Conclusion Our data provide support for the clinical significance of cfRNA markers in determining tumor subtypes and monitoring disease recurrence and therapy-induced subtype switches in pancreatic ductal adenocarcinoma (PDAC). Consequently, further validation studies in larger independent cohorts are warranted to confirm the robustness and generalizability of these findings.

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Section: Discussionmentioning

confidence: 99%

Minimally invasive determination of PDAC subtype and therapy-induced subtype switch by means of circulating cell-free RNA

Lueong,

Metzenmacher,

Trajkovic-Arsic

et al. 2024

Preprint

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“…Moreover, it is downregulated in LUAD and correlated with poor prognosis ( 61 ). IGHM is an immune-related gene encoding the C region of the µ heavy chain and defines its isoform ( 62 ). It significantly affects the density of infiltrating CD20 + B cells in tumor tissues ( 63 ).…”

Section: Discussionmentioning

confidence: 99%

Integrating single-cell and bulk RNA sequencing to develop a cancer-associated fibroblast-related signature for immune infiltration prediction and prognosis in lung adenocarcinoma

Huang¹,

Xiao²,

Shi³

et al. 2023

J Thorac Dis

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Background: An accumulating amount of studies are highlighting the impacts of cancer-associated fibroblasts (CAFs) on the initiation, metastasis, invasion, and immune evasion of lung cancer. However, it is still unclear how to tailor treatment regimens based on the transcriptomic characteristics of CAFs in the tumor microenvironment of patients with lung cancer.Methods: Our study examined single-cell RNA-sequencing data from the Gene Expression Omnibus (GEO) database to identify expression profiles for CAF marker genes and constructed a prognostic signature of lung adenocarcinoma using these genes in The Cancer Genome Atlas (TCGA) database. The signature was validated in 3 independent GEO cohorts. Univariate and multivariate analyses were used to confirm the clinical significance of the signature. Next, multiple differential gene enrichment analysis methods were used to explore the biological pathways related to the signature. Six algorithms were used to assess the relative proportion of infiltrating immune cells, and the relationship between the signature and immunotherapy response of lung adenocarcinoma (LUAD) was explored based on the tumor immune dysfunction and exclusion (TIDE) algorithm. Results:The signature related to CAFs in this study showed good accuracy and predictive capacity. In all clinical subgroups, the high-risk patients had a poor prognosis. The univariate and multivariate analyses confirmed that the signature was an independent prognostic marker. Moreover, the signature was closely associated with particular biological pathways related to cell cycle, DNA replication, carcinogenesis, and immune response. The 6 algorithms used to assess the relative proportion of infiltrating immune cells indicated that a lower infiltration of immune cells in the tumor microenvironment was associated with highrisk scores. Importantly, we found a negative correlation between TIDE, exclusion score, and risk score.Conclusions: Our study constructed a prognostic signature based on CAF marker genes useful for prognosis and immune infiltration estimation of lung adenocarcinoma. This tool could enhance therapy efficacy and allow individualized treatments.

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“…IL12RB1 has been reported that its mutation played a causal role in non-polyposis CRC pre-disposition. 38 Furthermore, the other three hub genes, IL2RB, XCR1 and CXCR6, have been reported to be related with the prognosis of other cancers, such as early breast cancer, 39 salivary adenoid cystic carcinoma, 40 bladder and hepatocellular cancers. 41,42 Obviously, the subtle quantitative information associated with gene expression would be missed in REO patterns.…”

Section: Discussionmentioning

confidence: 99%

Two novel qualitative transcriptional signatures robustly applicable to non‐research‐oriented colorectal cancer samples with low‐quality RNA

Cheng

Guo

Guan

et al. 2021

J Cellular Molecular Medi

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Currently, due to the low quality of RNA caused by degradation or low abundance, the accuracy of gene expression measurements by transcriptome sequencing (RNA‐seq) is very challenging for non‐research‐oriented clinical samples, majority of which are preserved in hospitals or tissue banks worldwide with complete pathological information and follow‐up data. Molecular signatures consisting of several genes are rarely applied to such samples. To utilize these resources effectively, 45 stage II non‐research‐oriented samples which were formalin‐fixed paraffin‐embedded (FFPE) colorectal carcinoma samples (CRC) using RNA‐seq have been analysed. Our results showed that although gene expression measurements were significantly affected, most cancer features, based on the relative expression orderings (REOs) of gene pairs, were well preserved. We then developed two REO‐based signatures, which consisted of 136 gene pairs for early diagnosis of CRC, and 4500 gene pairs for predicting post‐surgery relapse risk of stage II and III CRC. The performance of our signatures, which included hundreds or thousands of gene pairs, was more robust for non‐research‐oriented clinical samples, compared to that of two published concise REO‐based signatures. In conclusion, REO‐based signatures with relatively more gene pairs could be robustly applied to non‐research‐oriented CRC samples.

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A novel immune prognostic index for stratification of high-risk patients with early breast cancer

Cited by 5 publications

References 40 publications

Minimally invasive determination of PDAC subtype and therapy-induced subtype switch by means of circulating cell-free RNA

Minimally invasive determination of PDAC subtype and therapy-induced subtype switch by means of circulating cell-free RNA

Integrating single-cell and bulk RNA sequencing to develop a cancer-associated fibroblast-related signature for immune infiltration prediction and prognosis in lung adenocarcinoma

Two novel qualitative transcriptional signatures robustly applicable to non‐research‐oriented colorectal cancer samples with low‐quality RNA

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