Prognostic significance of SOCS1 and SOCS3 tumor suppressors and oncogenic signaling pathway genes in hepatocellular carcinoma
BACKGROUND: SOCS1 and SOCS3 genes are considered tumor suppressors in hepatocellular carcinoma (HCC) due to frequent epigenetic repression. Consistent with this notion, mice lacking SOCS1 or SOCS3 show increased susceptibility to diethylnitrosamine (DEN)-induced HCC. As SOCS1 and SOCS3 are important regulators of cytokine and growth factor signaling, their loss could activate oncogenic signaling pathways. Therefore, we examined the correlation between SOCS1/SOCS3 and key oncogenic signaling pathway genes as well as their prognostic significance in HCC.
METHODS: The Cancer Genome Atlas dataset on HCC comprising clinical and transcriptomic data was retrieved from the cBioportal platform. The correlation between the expression of SOCS1 or SOCS3 and oncogenic pathway genes was evaluated using the GraphPad PRISM software. The inversely correlated genes were assessed for their impact on patient survival using the UALCAN platform and their expression quantified in the regenerating livers and DEN-induced HCC tissues of mice lacking Socs1 or Socs3. Finally, the Cox proportional hazards model was used to evaluate the predictive potential of SOCS1 and SOCS3 when combined with the genes of select oncogenic signaling pathways.
RESULTS: SOCS1 expression was comparable between HCC and adjacent normal tissues, yet higher SOCS1 expression predicted favorable prognosis. In contrast, SOCS3 expression was significantly low in HCC, yet it lacked predictive potential. The correlation between SOCS1 or SOCS3 expression and key genes of the cell cycle, receptor tyrosine kinase, growth factor and MAPK signaling pathways were mostly positive than negative. Among the negatively correlated genes, only a few showed elevated expression in HCC and predicted survival. Many PI3K pathway genes showed mutual exclusivity with SOCS1 and/or SOCS3 and displayed independent predictive ability. Among genes that negatively correlated with SOCS1 and/or SOCS3, only CDK2 and AURKA showed corresponding modulations in the regenerating livers and DEN-induced tumors of hepatocyte-specific Socs1 or Socs3 deficient mice and predicted patient survival. The Cox proportional hazards model identified the combinations of SOCS1 or SOCS3 with CXCL8 and DAB2 as highly predictive.
CONCLUSIONS: SOCS1 expression in HCC has an independent prognostic value whereas SOCS3 expression does not. The predictive potential of SOCS1 expression is increased when combined with other oncogenic signaling pathway genes.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
|---|---|
| Enthalten in: |
BMC cancer - 20(2020), 1 vom: 17. Aug., Seite 774 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Khan, Md Gulam Musawwir [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 14.04.2021 Date Revised 14.04.2021 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1186/s12885-020-07285-3 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM313816972 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM313816972 | ||
| 003 | DE-627 | ||
| 005 | 20231225151406.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s12885-020-07285-3 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1046.xml |
| 035 | |a (DE-627)NLM313816972 | ||
| 035 | |a (NLM)32807134 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Khan, Md Gulam Musawwir |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Prognostic significance of SOCS1 and SOCS3 tumor suppressors and oncogenic signaling pathway genes in hepatocellular carcinoma |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 14.04.2021 | ||
| 500 | |a Date Revised 14.04.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: SOCS1 and SOCS3 genes are considered tumor suppressors in hepatocellular carcinoma (HCC) due to frequent epigenetic repression. Consistent with this notion, mice lacking SOCS1 or SOCS3 show increased susceptibility to diethylnitrosamine (DEN)-induced HCC. As SOCS1 and SOCS3 are important regulators of cytokine and growth factor signaling, their loss could activate oncogenic signaling pathways. Therefore, we examined the correlation between SOCS1/SOCS3 and key oncogenic signaling pathway genes as well as their prognostic significance in HCC | ||
| 520 | |a METHODS: The Cancer Genome Atlas dataset on HCC comprising clinical and transcriptomic data was retrieved from the cBioportal platform. The correlation between the expression of SOCS1 or SOCS3 and oncogenic pathway genes was evaluated using the GraphPad PRISM software. The inversely correlated genes were assessed for their impact on patient survival using the UALCAN platform and their expression quantified in the regenerating livers and DEN-induced HCC tissues of mice lacking Socs1 or Socs3. Finally, the Cox proportional hazards model was used to evaluate the predictive potential of SOCS1 and SOCS3 when combined with the genes of select oncogenic signaling pathways | ||
| 520 | |a RESULTS: SOCS1 expression was comparable between HCC and adjacent normal tissues, yet higher SOCS1 expression predicted favorable prognosis. In contrast, SOCS3 expression was significantly low in HCC, yet it lacked predictive potential. The correlation between SOCS1 or SOCS3 expression and key genes of the cell cycle, receptor tyrosine kinase, growth factor and MAPK signaling pathways were mostly positive than negative. Among the negatively correlated genes, only a few showed elevated expression in HCC and predicted survival. Many PI3K pathway genes showed mutual exclusivity with SOCS1 and/or SOCS3 and displayed independent predictive ability. Among genes that negatively correlated with SOCS1 and/or SOCS3, only CDK2 and AURKA showed corresponding modulations in the regenerating livers and DEN-induced tumors of hepatocyte-specific Socs1 or Socs3 deficient mice and predicted patient survival. The Cox proportional hazards model identified the combinations of SOCS1 or SOCS3 with CXCL8 and DAB2 as highly predictive | ||
| 520 | |a CONCLUSIONS: SOCS1 expression in HCC has an independent prognostic value whereas SOCS3 expression does not. The predictive potential of SOCS1 expression is increased when combined with other oncogenic signaling pathway genes | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Hepatocellular carcinoma | |
| 650 | 4 | |a Oncogenic signalling | |
| 650 | 4 | |a Prognosis | |
| 650 | 4 | |a SOCS1 | |
| 650 | 4 | |a SOCS3 | |
| 650 | 4 | |a TCGA | |
| 650 | 4 | |a Tumor suppressor | |
| 650 | 7 | |a Biomarkers, Tumor |2 NLM | |
| 650 | 7 | |a SOCS1 protein, human |2 NLM | |
| 650 | 7 | |a SOCS3 protein, human |2 NLM | |
| 650 | 7 | |a Socs1 protein, mouse |2 NLM | |
| 650 | 7 | |a Socs3 protein, mouse |2 NLM | |
| 650 | 7 | |a Suppressor of Cytokine Signaling 1 Protein |2 NLM | |
| 650 | 7 | |a Suppressor of Cytokine Signaling 3 Protein |2 NLM | |
| 650 | 7 | |a Diethylnitrosamine |2 NLM | |
| 650 | 7 | |a 3IQ78TTX1A |2 NLM | |
| 700 | 1 | |a Ghosh, Amit |e verfasserin |4 aut | |
| 700 | 1 | |a Variya, Bhavesh |e verfasserin |4 aut | |
| 700 | 1 | |a Santharam, Madanraj Appiya |e verfasserin |4 aut | |
| 700 | 1 | |a Ihsan, Awais Ullah |e verfasserin |4 aut | |
| 700 | 1 | |a Ramanathan, Sheela |e verfasserin |4 aut | |
| 700 | 1 | |a Ilangumaran, Subburaj |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t BMC cancer |d 2001 |g 20(2020), 1 vom: 17. Aug., Seite 774 |w (DE-627)NLM111431948 |x 1471-2407 |7 nnns |
| 773 | 1 | 8 | |g volume:20 |g year:2020 |g number:1 |g day:17 |g month:08 |g pages:774 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1186/s12885-020-07285-3 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 20 |j 2020 |e 1 |b 17 |c 08 |h 774 | ||