Identification of LSM Family Members as Novel Unfavorable Biomarkers in Hepatocellular Carcinoma

Abstract

BackgroundSmith-like (LSM) family members play critical roles in multiple oncologic processes in several types of malignancies. The study on LSM family members of HCC might provide new insights into the tumorigenesis and therapeutic strategies of HCC.MethodsThe clinical significance and oncologic biological functions of LSM family members were assessed through multiple bioinformatics methods and in vitro studies. The potential correlation between LSM family members and tumor immunity was also investigated using single sample gene set enrichment analysis (ssGSEA) and the ESTIMATE algorithm.ResultsLSM family member overexpression in HCC was significantly correlated with poor clinical outcomes such as higher TNM stage, advanced histologic grade, and worse prognosis. A risk score system based on LSM5, LSM10, LSM12, and LSM14B showed a reliable predictive ability for OS of HCC patients. Functional enrichment analysis demonstrated that LSM family members overexpressed were all involved in cell cycle related biological processes. Besides, LSM12, LSM14A, and LSM14B were found to be significantly associated with PI3K-Akt-mTOR and T cell receptor signaling pathways. Tumors with LSM12, LSM14A, and LSM14B overexpression exhibited lower infiltration of activated CD8+ T cells with declined cytolytic activity and immune score, but increased infiltration of Th2 cells and Th2/Th1. LSM12, LSM14A, and LSM14B overexpression is also associated with higher tumor-related immune checkpoints (e.g., PD-L1, B7-H3, and PVR) expression and increased therapeutic insensitivity to immune checkpoint blockade (ICB). Moreover, the knockdown of LSM12, LSM14A, and LSM14B significantly inhibited the proliferation and invasion of HCC cells.ConclusionThis study systematically investigated the expression pattern and biological values of LSM family members in HCC and identified LSM family members as novel therapeutic targets in HCC.

Identification of LSM family members as potential chemoresistance predictive and therapeutic biomarkers for gastric cancer

“…However, there is lack of studies on the role of LSM5 and LSM8 in tumors. Recent study revealed a risk score system consisting of LSM5 and identified it as a reliable predictive biomarker for hepatocellular cancer (28). So it is challenging but greatly significant to explore the underlying molecular mechanism about why LSM5 and LSM8 could be potential biomarkers for chemoresistant GC patients, we firstly analyzed the GO enrichment and KEGG annotation in GC.…”

LSM2 is associated with a poor prognosis and promotes cell proliferation, migration, and invasion in skin cutaneous melanoma

“…Therefore, LSM2 mRNA level was identified as an independent risk factor for shorter OS and PFS in SKCM. Similarly, some previous studies revealed that high LSM2 mRNA expression was significantly associated with poor OS in patients with BRCA [ 29 ] and HCC [ 31 ]. Thus, LSM2 may be an oncogene.…”

“…In addition, in the BioGPS database, LSM2 was found to be highly expressed in cutaneous melanoma cells compared to normal skin cells. Markedly upregulated LSM2 mRNA expression was also found in breast cancer (BRCA) [ 29 ], pancreatic ductal adenocarcinoma (PDAC) [ 30 ], and hepatocellular carcinoma (HCC) [ 31 ]. Germline variants and somatic mutations of LSM2, which belong to mRNA splicing-related genes, have been confirmed to be high-risk factors for lung cancer [ 21 , 32 ].…”

LSM12 facilitates the progression of colorectal cancer by activating the WNT/CTNNB1 signaling pathway

“…It is one of the main factors participating in DNA damage induced by oxidative stress [15]. Heretofore, the research on the function of LSM12 in human malignant tumors is still very limited [16][17][18]. Here, we demonstrated that LSM12 is involved in cytopathologic and tumorigenic functions during CRC development through the regulation of CTNNB1 protein stability and CTTNB1-LEF1-TCF1 transcriptional complex formation.…”