STAT2 Expression Is Higher in African American, Asian Patients With HCC

STAT2 expression in patients with hepatocellular carcinoma (HCC) increases with tumor grade and cancer stage, with increases occurring at greater rates among Asian and African American patients, according to findings from a retrospective study presented during the 5th Annual Regional Synergistic Partnership for Enhancing Equity in Cancer Health (SPEECH) Conference and Retreat in Philadelphia, Pennsylvania.¹

Findings from the study showed that patients with a primary liver tumor (n = 371) exhibited significantly higher levels of STAT2 mRNA expression compared with patients who did not have a primary liver tumor (n = 50; P = 3.79 x 10-9). Additionally, STAT2 expression was found to progressively increase with metastatic status and cancer stage. African American patients (n = 17) and Asian patients (n = 157) experienced higher levels of STAT2 mRNA compared with Caucasian patients (n = 177).

“Not only is there a link between [STAT2] and the presence of inflammation in cancer, but also a link between the levels of the transcription factor and different subgroups of patients,” Cal Harper, of Temple University, in Philadelphia, Pennsylvania, and the lead study author said in an interview with OncologyLive^®. “This is an important finding, just for the sake of research and updating the current literature, but also to continue finding better ways to treat different patients and treat each cancer as a different disease.”

STAT2 is a transcription factor that is a downstream effector of type I interferon signaling. The gene has been shown to inhibit or promote tumorigenesis, which is thought to be at least partially dependent on the specific tumor microenvironment. The role of STAT2 expression in the development of HCC specifically has not been well described.^1,2

To conduct their study, investigators used the interactive web resource UALCAN to analyze publicly available cancer transcriptome data sourced from The Cancer Genome Atlas database. Study authors wanted to examine overall expression of STAT2 mRNA in healthy individuals and those with a primary liver tumor, differentiate STAT2 expression in liver cancer subtypes, determine STAT2 expression by tumor and cancer stage, and compare STAT2 expression between male and female patients and patients of different ethnicities.¹

Additional results from the study revealed that patients with fibrolamellar carcinoma (n = 3) had approximately 20 more STAT2 mRNA transcripts per million compared with those with HCC (n = 361). Patients with HCC also had higher STAT2 expression compared with those without a primary liver tumor (P < .001) and those with fibrolamellar carcinoma had increased STAT2 expression vs patients with hepatocholangiocarcinoma (n = 7; P< .05).

In terms of metastatic status, there were approximately double the STAT2 transcripts per million among patients with N1 stage metastasis (n = 4) compared with those without a primary liver tumor (P < .001). Patients with N0 stage metastasis (n = 252) had a 50% increase in STAT2 transcripts per million compared with those with no liver tumor.

There was a median increase of 50% of STAT2 expression in all observed cancer stages (stages I-IV) compared with patients with no primary liver tumor. Additionally, STAT2 expression consistently rose through stages I through III; the rise at state IV was deemed not to be significant.

The next steps for this research include acquiring a broader sample size in terms of cancer stage and metastasis progression, as well as obtaining additional data from African American patients to further validate findings, according to Harper.

“STAT2 expression in patients with liver cancer is higher in African American and Asian patients than Caucasian patients,” Harper said in conclusion. “Not only is that significant [in terms of] treatment, but also because the African American sample size is only roughly 10% of the Caucasian sample size. We need to acquire a larger clinical cohort of those patients’ data. We also found similar findings with gender in that female patients typically have a higher expression of STAT2. There needs to be further clinical investigation to determine if [these findings are] statistically significant or not.”

References

1. Harper C, Dadey R, Alvarado A, Gamero AM. STAT2 gene expression increased in hepatocellular carcinoma but more predominantly in African Americans and Asian populations. Presented at: 5th Annual Regional Synergistic Partnership for Enhancing Equity in Cancer Health (SPEECH) Conference and Retreat; May 17-18, 2023; Philadelphia, PA. Poster 39.
2. Canar J, Darling K, Dadey R, Gamero AM. The duality of STAT2 mediated type I interferon signaling in the tumor microenvironment and chemoresistance. Cytokine. 2023;161:156081. doi:10.1016/j.cyto.2022.156081