Dysregulated patterns of long noncoding RNAs (lncRNAs), such as SOX9-AS1, may have both diagnostic and prognostic values in intrahepatic cholangiocarcinoma (iCCA), according to a recently published study in Clinics and Research in Hepatology and Gastroenterology.

Currently, surgical resection is the therapy of choice for patients with iCCA; however, due to the vagueness and late appearance of symptoms, as well as the limited diagnostic tools available, most patients have already advanced disease at the moment of diagnosis, which in turns limit eligibility for surgery and worsens the prognosis. Therefore, the interest in discovering biomarkers with diagnostic and prognostic value in iCCA has risen in recent years.

Developments in omics technology have permitted the identification of dysregulated patterns lncRNAs capable of influencing cancer genotype through dysregulation of target gene expression. One of these patterns, LncRNA SOX9-AS1, has been reported to have prognostic value in hepatocellular carcinoma.


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The authors aimed to study the value of LncRNA SOX9-AS1 in iCCA by measuring its plasma and tissue levels in patients with confirmed iCCA diagnosis and comparing it to those of healthy individuals, patients with hepatocellular carcinoma, and patients with extrahepatic cholangiocarcinoma (eCCA). The study included 107 patients from each of the groups mentioned above.

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Quantitative real-time reverse transcription-polymerase chain reaction was used to measure SOX9-AS1 levels. The comparison of SOX9-AS1 levels between different groups and cancer stages was made with the Student t-test while receiving operating characteristics and area under the curve were used to analyze predictive value.

Results revealed that LncRNA SOX9-AS1 was significantly higher in patients with iCCA compared with healthy individuals. Furthermore, the authors noted that SOX9-AS1 levels were directly correlated with advanced disease in patients with iCCA.

Comparing plasma SOX9-AS1 levels between iCCA, eCCA, and hepatocellular carcinoma showed increased levels in iCCA compared with the rest.

Patients with high SOX9-AS1 expression tended towards lower overall survival and recurrence-free survival compared to patients with low SOX9-AS1 expression. Knockdown of SOX9-AS1 had an inhibitory effect on cell proliferation and risk of metastasis, while overproliferation had the opposite effect.

“SOX9-AS1 can promote the cancerous behavior of [iCCA] cells. SOX9-AS1 might represent a promising strategy for the diagnosis prognosis, and personalized therapy in [iCCA],” the authors concluded.

Reference

Wu L, Yang J, Liu Y, et al. Impact of LNCRNA SOX9-AS1 overexpression on the prognosis and progression of intrahepatic cholangiocarcinoma. Clin Res Hepatol Gastroenterol. Published online July 20, 2022. doi:10.1016/j.clinre.2022.101999