Transcriptomic meta-analysis reveals up-regulation of gene expression functional in osteoclast differentiation in human septic shock

Mukhopadhyay, Samanwoy; Thatoi, Pravat Kumar; Pandey, AK; Das, B. K.; Ravindran, Balachandran; Bhattacharjee, Samsiddhi; Mohapatra, Saroj Kant

doi:10.1371/journal.pone.0171689

Cited by 13 publications

(15 citation statements)

References 24 publications

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“…Functionally, there is evidence of up-regulation of osteoclast differentiation and downregulation of antigen processing and presentation, T-cell receptor signaling ( Table 2). While immuno-suppression continues to be a recurring theme in sepsis biology, osteoclast differentiation has only recently been reported in our previous work in the context of septic shock with some evidence of its association with survival [12].…”

Section: Discussionmentioning

confidence: 92%

Immunosuppression, rather than inflammation, is a salient feature of sepsis in an Indian cohort

Mukhopadhyay

Thatoi

Das

et al. 2019

Preprint

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Sepsis remains a lethal ailment with imprecise treatment and ill-understood biology. A clinical transcriptomic analysis of sepsis patients was performed for the first time in India and revealed large-scale change in blood gene expression in patients of severe sepsis and septic shock admitted to ICU. Three biological processes were quantified using scores derived from the corresponding transcriptional modules. Comparison of the module scores revealed that genes associated with immune response were more suppressed compared to the inflammation-associated genes. These findings will have great implication in the treatment and prognosis of severe sepsis/septic shock if it can be translated into a bedside tool.

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Section: Discussionmentioning

confidence: 92%

Immunosuppression, rather than inflammation, is a salient feature of sepsis in an Indian cohort

Mukhopadhyay

Thatoi

Das

et al. 2019

Preprint

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“…Septic shock is a lethal condition with profound genome-scale change in expression. Earlier work in our laboratory had revealed cancer-associated pathways to be associated with septic shock [13], providing motivation for comparison of the transcriptomes between SS and cancer. By comprehensive transcriptome analysis of human septic 5/27 shock at the pathway level, we sought to capture the higher-order signal in the two clinical entities (sepsis and cancer).…”

Section: Discussionmentioning

confidence: 99%

“…Retrieved expression data were log2-transformed. Gene Set Enrichment Analysis (GSEA) on expression data of both cancer and SS was performed as published earlier [13]. Briefly, enrichment score (ES) for each pathway was calculated by dividing the sum of the gene-level log-fold changes with the square root of the pathway size.…”

Section: Methodsmentioning

confidence: 99%

Sepsis-associated Pathways Segregate Cancer Groups

Tripathi

Mukhopadhyay

Mohapatra

2019

Preprint

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AbstractBackgroundSepsis and cancer are both leading causes of death, and occurrence of any one, increases the likelihood of the other. While cancer patients are susceptible to sepsis, survivors of sepsis are also susceptible to develop certain cancers. This mutual dependence for susceptibility suggests shared biology between the two disease categories. Earlier analysis had revealed cancer-related pathway to be up-regulated in Septic Shock (SS), an advanced stage of sepsis. This has motivated a more comprehensive comparison of the transcriptomes of SS and cancer.MethodsGene Set Enrichment Analysis was performed to detect the pathways enriched in SS and cancer. Thereafter, hierarchical clustering was applied to identify relative segregation of 17 cancer types in to two groups vis-a-vis SS. Biological significance of the selected pathways was explored by network analysis. Clinical significance of the pathways was tested by survival analysis. A robust classifier of cancer groups was developed based on machine learning.ResultsA total of 66 pathways were observed to be enriched in both SS and cancer. However, clustering segregated cancer types into two categories based on the direction of transcriptomic change. In general, there was up-regulation in SS and one group of cancer (termed Sepsis-Like Cancers, or SLC), but not in other cancers. SLC group mainly consisted of malignancies of the gastrointestinal tract (head and neck, oesophagus, stomach, liver and biliary system) often associated with infection. Machine learning classifier successfully segregated the two cancer groups with high accuracy (> 98%). Additionally, pathway up-regulation was observed to be associated with survival in the SLC group of cancers.ConclusionTranscriptome-based systems biology approach segregates cancer into two groups (SLC and CA) based on similarity with SS. Host response to infection plays a key role in pathogenesis of SS and SLC. However, we hypothesize that some component of the host response is protective in both SS and SLC.

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“…Both the diseases are associated with anaerobic metabolism with lactic acidosis being a hallmark of septic shock [9,11]. In our earlier work, we have observed a cancer associated pathway to be significantly up-regulated in septic shock [12]. Additionally, there are previous reports on shared molecular changes in sepsis and cancer.…”

Section: Introductionmentioning

confidence: 90%

“…Six studies of septic shock (SS) were selected following the procedure described earlier [12]. Normalized gene expression data from the series matrix files were retrieved from NCBI Gene Expression Omnibus (GEO) database (https:// www.ncbi.nlm.nih.gov/geo/) on April 10, 2019.…”

Section: Geo Datamentioning

confidence: 99%

Sepsis-associated pathways segregate cancer groups

2020

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Background: Sepsis and cancer are both leading causes of death, and occurrence of any one, increases the likelihood of the other. While cancer patients are susceptible to sepsis, survivors of sepsis are also susceptible to develop certain cancers. This mutual dependence for susceptibility suggests shared biology between the two disease categories. Earlier analysis had revealed a cancer-related pathway to be up-regulated in Septic Shock (SS), an advanced stage of sepsis. This has motivated a more comprehensive comparison of the transcriptomes of SS and cancer.

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Transcriptomic meta-analysis reveals up-regulation of gene expression functional in osteoclast differentiation in human septic shock

Cited by 13 publications

References 24 publications

Immunosuppression, rather than inflammation, is a salient feature of sepsis in an Indian cohort

Immunosuppression, rather than inflammation, is a salient feature of sepsis in an Indian cohort

Sepsis-associated Pathways Segregate Cancer Groups

Sepsis-associated pathways segregate cancer groups

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