ACE2 and FZD1 are prognosis markers in squamous cell/adenosquamous carcinoma and adenocarcinoma of gallbladder

Abstract

The clinicopathological characteristics of squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder have not been well documented, and no prognosis marker has been identified because of the rare occurrence of this gallbladder cancer subtype. In this study, we examined ACE2 and FZD1 expression in 46 SC/ASCs and 80 adenocarcinomas using immunohistochemistry and further analyzed their correlations with clinicopathological characteristics. We demonstrated that positive FZD1 and negative ACE2 expression were significantly associated with large tumor size, high TNM stage, lymph node metastasis and invasion of SC/ASC and AC. Univariate Kaplan-Meier analysis showed that positive FZD1 and negative ACE2 expression as well as differentiation, tumor size, TNM stage, lymph node metastasis, invasion, and surgical curability were closely associated with decreased overall survival in both SC/ASC (p < 0.001) and AC (p < 0.001) patients. The average survival time in SC/ASC and AC patients with FZD1(-)ACE2(+) expression was significantly longer than that in patients with FZD1(+)ACE2(-) or FZD1(+)ACE2(+) (p < 0.01). Multivariate Cox regression analysis showed that positive FZD1 and negative ACE2 expression are independent poor-prognostic factors for both SC/ASC and AC patients. In addition, FZD1 expression positively, but ACE2 expression negatively correlated with the expression of CA19-9 in SC/ASC and AC. Our study suggested that positive FZD1 and negative ACE2 expression are closely related to the expression of CA19-9; clinical, pathological, and biological behaviors; as well as poor-prognosis of gallbladder cancer.

ACE2 correlated with immune infiltration serves as a prognostic biomarker in endometrial carcinoma and renal papillary cell carcinoma: implication for COVID-19

“…A study carried out by Yu X et al [39] showed that ACE2 can block the inflammatory response of pancreatic acinar cells by blocking the p38 MAPK/NF-κB signaling pathway. Li J et al [40] examined the role of ACE2 and FZD1 in squamous cell/adenosquamous carcinoma (SC / ASC) of the gallbladder, the results showed that negative ACE2 expression in SC/ASC was associated with high TNM stage and lymph node metastasis, and survival analysis showed ACE2 and SC/ASC overall survival were positively correlated. ACE2 was also decreased in nonsmall cell lung cancer (NSCLC), but overexpression of ACE2 in vitro exerted protective effects by inhibiting cell growth and VEGFa production [41].…”

Gallbladder Cancer in the 21st Century

“… Frizzled (FZD1) is a member of a family of transmembrane receptors to which Wnt genes bind; these genes are well recognized to play a key role in controlling proliferation, specification, polarity, and cell migration. Expression of FZD1 is significantly associated with a large tumour size, high TMN staging, and lymph node involvement, with increased propensity for invasion, and thereby it is associated with a decreased overall survival in patients with gallbladder squamous cell and adenocarcinomas [ 169 ]. …”

Pure squamous cell carcinoma of the gallbladder locally invading the liver and abdominal cavity: A case report and review of the literature

“…Generally, SCC is aggressive, with infiltration into the liver, and rarely metastasizes to lymph nodes[4]. The clinicopathological and biological features of SCC remain to be fully elucidated[5,6], owing to its uncommon occurrence. The majority of currently available data only described individual case reports or series analyses of trivial cases.…”

“…The majority of currently available data only described individual case reports or series analyses of trivial cases. Therefore, it is imperative to describe the clinicopathological and biological features of SCC[5,6]. To improve our understanding of SCC of the gallbladder, we conducted a retrospective case study and review of the literature[6].…”