Abstract
The neurotransmitter, serotonin has emerged as a tumor growth factor and immune response regulator through complex signaling pathways. Yip1 Interacting Factor Homolog B (YIF1B) is a membrane protein involved in serotonin receptor (HTR) membrane trafficking and signal transmission in neuropathy. Participation of YIF1B in serotonin-induced tumor growth and immune regulation has not been previously investigated. Data for analysis of YIF1B mRNA expression were downloaded from the website portals: The Cancer Genome Atlas (TCGA), GTEx, Cancer Cell Line Encyclopedia (CCLE) and International Cancer Genome Consortium (ICGC), including clinical and mutational information. Survival analysis included the Kaplan–Meier method for calculation of the cumulative incidence of the survival event and the log rank method for comparison of survival curves between groups. Infiltration levels of immune cells were calculated and correlated with YIF1B expression using the Spearman correlation test to evaluate significance. Further correlation analyses between YIF1B expression and mutation indicators such as tumor mutation burden (TMB), microsatellite instability (MSI), and mismatch repair (MMR) were also examined by the Spearman test. YIF1B expression was elevated in most cancer types and this high expression was indicative of poor overall survival (OS) and death-specific survival. In breast invasive carcinoma (BRCA) and liver hepatocellular carcinoma (LIHC), high YIF1B expression correlated with a poor disease-free interval (DFI), indicating a role in malignancy progression. There was a positive relationship between YIF1B expression and immune cell infiltration in several cancer types, and YIF1B also positively correlated with TMB, MSI, and methylation in some cancer types, linking its expression to possible evaluation of therapy response. The bioinformatics analyses have, therefore, established YIF1B as a good biomarker for prognostic and therapeutic evaluation.
Highlights
Serotonin, a known neurotransmitter, has recently emerged as a tumor growth factor for several human cancers through interaction with its receptors (5-serotonin receptor (HTR) 1–7), which are widely expressed across a range of tissues [1,2]
Further comparison between relatively normal tissues and respective tumors showed Yip1 Interacting Factor Homolog B (YIF1B) was highly expressed in most tumors, apart from the kidney chromophobe (KICH), which showed the reverse result with significance
The kidney renal clear cell carcinoma (KIRC) and THCA cohorts showed similar expression levels between tumor and normal tissues, and KICH and acute myeloid leukemia (LAML) tumor tissues had decreased expression of YIF1B compared with normal tissues (Figure 1C,D)
Summary
A known neurotransmitter, has recently emerged as a tumor growth factor for several human cancers through interaction with its receptors (5-HTR 1–7), which are widely expressed across a range of tissues [1,2]. Membrane-bound YIF1B directly associates with the C-terminal region of the 5-HT1A receptor, interfering with binding of serotonin to the distal part of the receptor. This observation has led to targeting of the process in development of treatments for depression [12,13]. The results identify YIF1B as a new prognostic marker for malignancy and an immune therapy response indicator in most cancer types. It may serve as a potential target for cancer therapy, especially in some low-response tumors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
