Abstract: Objective To investigate the gene mutation spectrum of colorectal cancer (CRC) and the mediated molecular mechanism of CRC immune resistance. Methods A total of 36 CRC patients admitted to Guangxi Medical University Cancer Hospital from January 2019 to January 2020 were selected. New generation sequencing(NGS) was used to detect the gene mutation spectra in tissue and blood samples. The mutation spectra were described by molecular network events, TIMER and CancerSEA database were used to analyze the immune infiltration and tissue single cell distribution of core molecules, Reactome database was used for functional clustering analysis of core molecules, and the STRING database was used to analyze the core immune resistance event network. Results The results of tissue and blood samples showed that stromal interaction molecule 1(STIM1) was the screened high frequency mutation gene (The mutation frequency was 97.2%). Immune infiltration and single cell distribution showed that STIM1, RELA and JUN were involved in immune response. The expressions of STIM1, RELA and JUN mRNA in colon cancer patients were significantly correlated with the infiltration level of CD4+ T cells(r=0.554, 0.565, 0.319; all P<0.05). Meanwhile, RELA and JUN were positively correlated with STIM1(r=0.579, 0.223；all P<0.05). Kaplan-Meier analysis indicated that the higher the infiltration levels of CD4+ T cells and macrophages are, the worse the survival prognosis of colorectal cancer patients is. Functional cluster analysis identified that STIM1 was related to adaptive immune system, innate immune system, cytokine signaling in the immune system and ubiquitination modification of immunoreactive proteins, while PPI network analysis showed that STIM1 was related to RELA and JUN. Conclusions STIM1 may join RELA and JUN to form an immune resistance network, and becomes an important regulatory factor and potential therapeutic target in CRC immune resistance.

Key words: Colorectal cancer, Immune resistance, STIM1, RELA, JUN, Molecular mechanism