Note for: Ring finger protein 43 expression is associated with genetic alteration status and poor prognosis among patients with intrahepatic cholangiocarcinoma

Paper: Ring finger protein 43 expression is associated with genetic alteration status and poor prognosis among patients with intrahepatic cholangiocarcinoma

(doi: 10.1016/j.humpath.2015.12.027)

Marks -- P < .05, considered statistically significant (even for Kaplan-Meier analysis)
Abstract;
RNF43--
1.central maintenance of genome integrity
2.cellular homeostasis

Ring finger ligases --
involve in malignancy

RNF43 --
frequently mutated in many type of malignancy (ICC is part of this malignancy)

Gap;
Expression level of RNF43 in ICC never been observed

Purposed;
1.Investigate expression level in ICC
2.Identify RNF43 polymorphisms in ICC tissues
3.Observe correlation between RNF43 expression vs RNF43 mutation/polymorphisms, clinicopathological features and prognosis

Finding;
1.RNF43 low correlated with rs2257205 and RNF43-somatic mutations
2.down reg of RNF43 (both protein and mRNA level) related to overall survival poor (meaning RNF43 could play role as tumor suppressor)
3.RNF43 expression level is not correlated with the protein level (like in the case of PDCA), clinicopathological feature, and RNF43 polymorphisms (this means protein level might play more role as predictive tool for cancer progression?)

Newly implicated gene found in ICC cases -- RNF43 mutation (9.3%) of ICC casesCriteria;
-50 FFPE and 28/50 frozen tissues
-no treatment cancer treatment
-follow the patients from operation to death/4 years follow up
-using exome sequencing from previous study
-identify polymorphism based on dbSNP131 and 132 databases

non-tumorous tissue;
RNF43 expressed in the nucleus of
1.hepatocyte
2.normal bile duct epithelium


RNF43 protein expressions are varied as seen in the Table1


Survival curve to see the relationship between overall survival and protein expression level

Very heterogeneity for ICC


RNF43 mRNA expressions are varied as seen in the Table3


Survival curve to see the relationship between overall survival and mRNA expression level

Conclusion;
Functional aberration of RN43 can be either tumor suppressor or oncogene depending on the tumor type.

For ICC -- RNF43 acts as a tumor suppressor since both survival rate is decreased when either mRNA or protein expression level is down-regulated.

decreased expression of RNF43/somatic mutations -- poor prognostic marker

question remains on;
down-regulation of RNF43 in ICC is still unclear in the term of the mechanism.