Tumour-stroma ratio and 5-year mortality in gastric adenocarcinoma: a systematic review and meta-analysis

Kemi, Niko; Eskuri, Maarit; Kauppila, Joonas H.

doi:10.1038/s41598-019-52606-7

Cited by 27 publications

(23 citation statements)

References 30 publications

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“…The majority of previous studies have indicated a negative prognostic impact of a dense tumour stroma, most often measured as the tumour stroma ratio (TSR), e.g. in colorectal cancer [16] , [17] , [18] , gastric cancer [19] , breast cancer [ 20 , 21 ], cervical cancer [22] , and oesophageal squamous cell cancer [23] . This association was also confirmed in a meta-analysis including 14 studies of different cancer types [12] .…”

Section: Discussionmentioning

confidence: 99%

The prognostic impact of the tumour stroma fraction: A machine learning-based analysis in 16 human solid tumour types

et al. 2021

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Background The development of a reactive tumour stroma is a hallmark of tumour progression and pronounced tumour stroma is generally considered to be associated with clinical aggressiveness. The variability between tumour types regarding stroma fraction, and its prognosis associations, have not been systematically analysed. Methods Using an objective machine-learning method we quantified the tumour stroma in 16 solid cancer types from 2732 patients, representing retrospective tissue collections of surgically resected primary tumours. Image analysis performed tissue segmentation into stromal and epithelial compartment based on pan-cytokeratin staining and autofluorescence patterns. Findings The stroma fraction was highly variable within and across the tumour types, with kidney cancer showing the lowest and pancreato-biliary type periampullary cancer showing the highest stroma proportion (median 19% and 73% respectively). Adjusted Cox regression models revealed both positive (pancreato-biliary type periampullary cancer and oestrogen negative breast cancer, HR(95%CI)=0.56(0.34-0.92) and HR(95%CI)=0.41(0.17-0.98) respectively) and negative (intestinal type periampullary cancer, HR(95%CI)=3.59(1.49-8.62)) associations of the tumour stroma fraction with survival. Interpretation Our study provides an objective quantification of the tumour stroma fraction across major types of solid cancer. Findings strongly argue against the commonly promoted view of a general associations between high stroma abundance and poor prognosis. The results also suggest that full exploitation of the prognostic potential of tumour stroma requires analyses that go beyond determination of stroma abundance. Funding The Swedish Cancer Society, The Lions Cancer Foundation Uppsala, The Swedish Government Grant for Clinical Research, The Mrs Berta Kamprad Foundation, Sweden, Sellanders foundation, P.O.Zetterling Foundation, and The Sjöberg Foundation, Sweden.

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Section: Discussionmentioning

confidence: 99%

The prognostic impact of the tumour stroma fraction: A machine learning-based analysis in 16 human solid tumour types

et al. 2021

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“…It is worth noting that intratumor stroma proportions have been proposed as significant indicators of GC prognosis (Lee et al, 2017). Previous studies have suggested that a high matrix proportion in GC patients means a poor prognosis (Ham, Lee & Hur, 2019;Kemi, Eskuri & Kauppila, 2019;Lee et al, 2017). Collagen genes play a crucial role in cell matrix formation, and their abnormal expression may lead to changes in matrix proportions.…”

Section: Discussionmentioning

confidence: 99%

Identifying multiple collagen gene family members as potential gastric cancer biomarkers using integrated bioinformatics analysis

Liu

Shao

et al. 2020

PeerJ

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Background Gastric cancer is one of the most common malignant cancers worldwide. Despite substantial developments in therapeutic strategies, the five-year survival rate remains low. Therefore, novel biomarkers and therapeutic targets involved in the progression of gastric tumors need to be identified. Methods We obtained the mRNA microarray datasets GSE65801, GSE54129 and GSE79973 from the Gene Expression Omnibus database to acquire differentially expressed genes (DEGs). We used the Database for Annotation, Visualization, and Integrated Discovery (DAVID) to analyze DEG pathways and functions, and the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape to obtain the protein–protein interaction (PPI) network. Next, we validated the hub gene expression levels using the Oncomine database and Gene Expression Profiling Interactive Analysis (GEPIA), and conducted stage expression and survival analysis. Results From the three microarray datasets, we identified nine major hub genes: COL1A1, COL1A2, COL3A1, COL5A2, COL4A1, FN1, COL5A1, COL4A2, and COL6A3. Conclusion Our study identified COL1A1 and COL1A2 as potential gastric cancer prognostic biomarkers.

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“…Additional data, including height, BMI, FAO p and ETS, were included when available. Externally sourced data were extracted using WebPlotDigitizer 109 (Web Plot Digitizer, v.4.2, 2019, Ankit Rohatgi, https://autom eris.io/WebPl otDig itizer, Pacifica, California, USA) [110][111][112][113] if not presented in table or text. Verification of data extraction accuracy was substantiated using a subset of our own publications 94,108,114,115 to compare extracted values to the actual measured values (n = 80).…”

Section: External Data Extractionmentioning

confidence: 99%

Contextualizing the biological relevance of standardized high‐resolution respirometry to assess mitochondrial function in permeabilized human skeletal muscle

Jacobs

Lundby

2021

Acta Physiologica

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Aim This study sought to provide a statistically robust reference for measures of mitochondrial function from standardized high‐resolution respirometry with permeabilized human skeletal muscle (ex vivo), compare analogous values obtained via indirect calorimetry, arterial‐venous O2 differences and 31P magnetic resonance spectroscopy (in vivo) and attempt to resolve differences across complementary methodologies as necessary. Methods Data derived from 831 study participants across research published throughout March 2009 to November 2019 were amassed to examine the biological relevance of ex vivo assessments under standard conditions, ie physiological temperatures of 37°C and respiratory chamber oxygen concentrations of ~250 to 500 μmol/L. Results Standard ex vivo‐derived measures are lower (Z ≥ 3.01, P ≤ .0258) en masse than corresponding in vivo‐derived values. Correcting respiratory values to account for mitochondrial temperatures 10°C higher than skeletal muscle temperatures at maximal exercise (~50°C): (i) transforms data to resemble (Z ≤ 0.8, P > .9999) analogous yet context‐specific in vivo measures, eg data collected during maximal 1‐leg knee extension exercise; and (ii) supports the position that maximal skeletal muscle respiratory rates exceed (Z ≥ 13.2, P < .0001) those achieved during maximal whole‐body exercise, e.g. maximal cycling efforts. Conclusion This study outlines and demonstrates necessary considerations when actualizing the biological relevance of human skeletal muscle respiratory control, metabolic flexibility and bioenergetics from standard ex vivo‐derived assessments using permeabilized human muscle. These findings detail how cross‐procedural comparisons of human skeletal muscle mitochondrial function may be collectively scrutinized in their relationship to human health and lifespan.

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Tumour-stroma ratio and 5-year mortality in gastric adenocarcinoma: a systematic review and meta-analysis

Cited by 27 publications

References 30 publications

The prognostic impact of the tumour stroma fraction: A machine learning-based analysis in 16 human solid tumour types

The prognostic impact of the tumour stroma fraction: A machine learning-based analysis in 16 human solid tumour types

Identifying multiple collagen gene family members as potential gastric cancer biomarkers using integrated bioinformatics analysis

Contextualizing the biological relevance of standardized high‐resolution respirometry to assess mitochondrial function in permeabilized human skeletal muscle

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