Different results between papers and GEO2R

Question

[cagdas]

Hi,

I performed a DE miRNAs analyses via GEO2R for https://www.ncbi.nlm.nih.gov/geo/geo2r/?acc=GSE78775. I obtained an upregulation for miR-148a in tumors compared with normal. When I search miR-148a in Pubmed, unfortunately a lot of paper say it is downregulated (in exp., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982598/). Could you help me to interpret the GEO2R results or re-perform the analyses according to your codes / softwares, please?

Thanks

[GenoMax]

May sound trivial but did you confirm the comparison order of the classes/groups in your analysis?

[cagdas]

Yes, I confirmed it, no problem...

[Kevin Blighe]

There is something strange happening. You may have to contact the authors:

library(Biobase)
library(GEOquery)

# load series and platform data from GEO
gset <- getGEO("GSE78775", GSEMatrix =TRUE, getGPL=FALSE)
if (length(gset) > 1) idx <- grep("GPL10850", attr(gset, "names")) else idx <- 1
gset <- gset[[idx]]

rownames(gset)[grep('miR-148a', rownames(gset))]
[1] "hsa-miR-148a"  "hsa-miR-148a*"

data <- data.frame(
  Tissue = pData(gset)[,'tissue:ch1'],
  miR148a = exprs(gset)[grep('miR-148a', rownames(gset)),][1,])
head(data)
           Tissue  miR148a
GSM2076383  tumor 7.218001
GSM2076384 normal 5.356292
GSM2076385  tumor 9.058600
GSM2076386 normal 6.050635
GSM2076387  tumor 7.393683
GSM2076388 normal 5.517655


par(mfrow = c(1,2))
boxplot(miR148a ~ Tissue, data, main = 'miR-148')
data <- data.frame(
  Tissue = pData(gset)[,'tissue:ch1'],
  miR148a = exprs(gset)[grep('miR-148a', rownames(gset)),][2,])
head(data)
           Tissue     miR148a
GSM2076383  tumor 0.053578910
GSM2076384 normal 0.026429820
GSM2076385  tumor 0.032966353
GSM2076386 normal 0.002947842
GSM2076387  tumor 0.014932436
GSM2076388 normal 0.025117474

boxplot(miR148a ~ Tissue, data, main = 'miR-148*')

[cagdas]

Kevin thank you for your detailed reply.

[cagdas]

Also following paper had found a downregulation. What can be the problem Kevin? https://www.nature.com/articles/s10038-020-0746-6

[Kevin Blighe]

Not for me to follow-up - I would clarify with the authors. This miR is clearly up-regulated in tumor, judging by the box-and-whiskers plot (above). Perhaps the authors are segregating by sex|gender, though (?)

[Kevin Blighe]

They may have made a mistake with their metadata - not sure.

[fernardo]

Even in their published work (Paper), they stated that this miRNA is down-regulated in GC patients. I believe they mixed the samples between tumor and normal when uploaded to GEO . As the others mentioned, best to check with author.