Gallbladder cancer (GBC) is the fifth most frequently diagnosed malignancy of the biliary tract, accounting for 80–95% of biliary tract cancers worldwide [1]. The incidence of GBC demonstrates significant geographical variation, with the highest rates reported in South America and Asia, and lower rates in North America. In Shanghai, China, the frequency of GBC is steadily increasing. Unfortunately, the majority of GBC cases are diagnosed at an advanced stage, attributed to the tumor's aggressive behavior and early metastasis [2]. Surgical resection of gallbladder tumors remains the most effective therapy [3]. However, even after complete resection, the recurrence rate is high and significantly impacts the prognosis of GBC patients. On average, the survival time ranges from 13.2 to 19 months, with a 5-year survival rate of less than 5% [4]. Hence, there is a pressing need for a deeper understanding of the underlying molecular mechanisms driving GBC to develop effective therapeutic targets.

The SIRT family (SIRT1–7) comprises a group of NAD+-dependent deacetylases and ADP-ribosyltransferases that play crucial roles in pressure resistance, genomic stability, energy metabolism, and aging [5]. Among these seven sirtuin members, SIRT7 is the least understood in terms of its enzymatic activities and functions. It is the only sirtuin localized to the nucleosome and is involved in deacetylating H3K18ac and H3K122, contributing to the maintenance of oncogenic transformation and regulation of chromatin remodeling during DNA repair [6]. Recent studies have revealed that SIRT7 exhibits distinct roles, acting both as an oncogene and as a tumor suppressor in different types of cancer [7], [8], [9], [10], [11], [12], [13], [14]. For instance, SIRT7 promotes the progression of pancreatic cancer [7], while it inhibits distant metastasis in breast cancer [14]. However, the specific role of SIRT7 in gallbladder cancer remains largely unexplored. This is due, in part, to the scarcity of expression profile data and prognostic information for gallbladder cancer patients in the TCGA database. Moreover, no studies have investigated the relationship between SIRT7 and gallbladder cancer to date. Therefore, our understanding of the association between SIRT7 and GBC is currently limited. Given the high malignancy and poor prognosis of gallbladder cancer, it is crucial to gain deeper insights into the role of SIRT7 in this particular tumor type. By elucidating the involvement of SIRT7, we can potentially identify new therapeutic targets and strategies for the management of GBC.

Through immunohistochemistry on a tissue microarray, we determined the protein levels of SIRT7 in GBC samples. By correlating these levels with clinicopathological parameters, such as tumor stage, grade, and patient outcomes, we aimed to evaluate the potential prognostic value of SIRT7 in GBC. In addition to the clinical analysis, we conducted in vitro experiments using the GBC-SD cell line. By manipulating the expression of SIRT7, either through interference or overexpression, we assessed its impact on various cellular processes, including proliferation, migration, invasion, cell cycle regulation, and apoptosis in GBC cells. Furthermore, we specifically investigated the involvement of the NF-κB pathway, which has been implicated in cancer progression and treatment resistance. By examining the potential mechanistic links between SIRT7 and the NF-κB pathway, we aimed to gain a deeper understanding of the underlying molecular mechanisms and signaling pathways associated with SIRT7 in GBC.