The effect of Vasohibin-1 expression and tumor-associated macrophages on the angiogenesis in vitro and in vivo

Peer reviewe

Tumor-associated macrophages regulate gastric cancer cell invasion and metastasis through TGF beta 2/NF-kappa B/Kindlin-2 axis

Objective: Recent studies have shown that tumor-associated macrophages (TAMs) play an important role in cancer invasion and metastasis. Our previous studies have reported that TAMs promote the invasion and metastasis of gastric cancer (GC) cells through the Kindlin-2 pathway. However, the mechanism needs to be clarified. Methods: THP-1 monocytes were induced by PMA/interleukin (IL)-4/IL-13 to establish an efficient TAM model in vitro and M2 macrophages were isolated via flow cytometry. A dual luciferase reporter system and chromatin immunoprecipitation (ChIP) assay were used to investigate the mechanism of transforming growth factor beta 2 (TGF beta 2) regulating Kindlin-2 expression. Immunohistochemistry was used to study the relationships among TAM infiltration in human GC tissues, Kindlin-2 protein expression, clinicopathological parameters and prognosis in human GC tissues. A nude mouse oncogenesis model was used to verify the invasion and metastasis mechanisms in vivo. Results: We found that Kindlin-2 expression was upregulated at both mRNA and protein levels in GC cells cocultured with TAMs, associated with higher invasion rate. Kindlin-2 knockdown reduced the invasion rate of GC cells under coculture condition. TGF beta 2 secreted by TAMs regulated the expression of Kindlin-2 through the transcription factor NF-kappa B. TAMs thus participated in the progression of GC through the TGF beta 2/NF-kappa B/Kindlin-2 axis. Kindlin-2 expression and TAM infiltration were significantly positively correlated with TNM stage, and patients with high Kindlin-2 expression had significantly poorer overall survival than patients with low Kindlin-2 expression. Furthermore, Kindlin-2 promoted the invasion of GC cells in vivo. Conclusions: This study elucidates the mechanism of TAMs participating in GC cell invasion and metastasis through the TGF beta 2/NF-kappa B/Kindlin-2 axis, providing a possibility for new treatment options and approaches.Peer reviewe

Risk of suicide in patients with thyroid cancer: protocol for a systematic review and meta-analysis

Introduction In recent years, the incidence of thyroid cancer has increased manyfold and young adults, who have a greater financial burden and occupational stress, comprise a large number. Previous studies have shown mixed results, even distinct results, on suicide rates among thyroid cancer survivors. As the overdiagnosis and overtreatment of thyroid cancer has gradually become a topical issue, the study aims to summarise the risk of suicide among patients with thyroid cancer to provide robust evidence of the effects of thyroid cancer on suicide.Methods and analysis A total of six databases (MEDLINE, Embase, Web of Science Core Collection, PsycINFO, CINAHL and Google Scholar) will be searched according to MeSH, subheadings, and free words, and the planned search date is 31 Jnauary 2024. The search strategy had three parts, such as suicide, cancer and epidemiological studies, moreover, we will collect the detailed suicide information by reviewers’ extraction. Standard mortality ratio (SMR) was used as the outcome measure, when SMRs were not available, the risk ratio, HR and detailed number of suicides were extracted to calculate the SMRs.Ethics and dissemination The Institutional Review Board of Peking University People’s Hospital provided ethical approval exemption and approved the data collection and subsequent analyses in accordance with the Declaration of Helsinki as revised in 2013.PROSPERO registration number CRD42023445542

Young adults with colon cancer: clinical features and surgical outcomes

Abstract Background The clinicopathological features, surgical outcomes, and long-term survival of patients with young-onset colon cancer (≤ 40 years old) remain controversial. Methods The clinicopathologic and follow-up data of patients aged < 40 years with colon cancer between January 2014 and January 2022 were reviewed. The primary objectives were clinical features and surgical outcomes. Long-term survival was investigated as a secondary objective. Results Seventy patients were included in the study, and no significant rising trend (Z=0, P=1) of these patients was observed over the 8-year study period. Stage IV disease was accompanied by more ulcerative or infiltrating type (84.2% vs. 52.9%, P=0.017) and lymphovascular or perineural invasion (64.7% vs. 25.5%, P=0.003) than stage I–III disease. After a median follow-up time of 41 months (range 8–99 months), the 1-, 3-, and 5-year estimated overall survival (OS) rates were 92.6%, 79.5%, and 76.4%, respectively. The 1-, 3-, and 5-year progression-free survival (PFS) rates were 79.6%, 71.7%, and 71.7%, respectively. Multivariate Cox regression showed that M+ stage (hazard ratio [HR], 3.942; 95% confidence interval [CI], 1.176–13.220, P=0.026) was the only independent risk factor affecting OS. Meanwhile, tumor deposits (HR, 4.807; 95% CI, 1.942–15.488, P=0.009), poor differentiation (HR, 2.925; 95% CI, 1.012–8.454, P=0.047), and M+ stage (HR, 3.540; 95% CI, 1.118–11.202, P=0.032) independently affected PFS. Conclusions The differences in the clinical features, surgical outcomes, and long-term survival between young adults and elderly colon cancer patients need further investigation

Prognostic Biomarker SPOCD1 and Its Correlation with Immune Infiltrates in Colorectal Cancer

The biological role of the spen paralogue and orthologue C-terminal domain containing 1 (SPOCD1) has been investigated in human malignancies, but its function in colorectal cancer (CRC) is unclear. This study investigated the association between SPOCD1 expression and clinicopathological features of CRC cases, as well as its prognostic value and biological function based on large-scale databases and clinical samples. The results showed that the expression level of SPOCD1 was elevated in CRC, which was generally associated with shortened survival time and poor clinical indexes, including advanced T, N, and pathologic stages. Multivariate Cox regression analysis showed that elevated SPOCD1 expression was an independent factor for poor prognosis in CRC patients. Functional enrichment analysis of SPOCD1 and its co-expressed genes revealed that SPOCD1 could act as an oncogene by regulating gene expression in essential functions and pathways of tumorigenesis, such as extracellular matrix organization, chemokine signaling pathways, and calcium signaling pathways. In addition, immune cell infiltration results showed that SPOCD1 expression was associated with various immune cells, especially macrophages. Furthermore, our findings suggested a possible function for SPOCD1 in the polarization of macrophages from M1 to M2 in CRC. In conclusion, SPOCD1 is a promising diagnostic and prognostic marker for CRC, opening new avenues for research and treatment

Global-scale profiling of differential expressed lysine acetylated proteins in colorectal cancer tumors and paired liver metastases

Lysine acetylated modification was indicated to impact colorectal cancer (CRC)'s distant metastasis. However, the global acetylated proteins in CRC and the differential expressed acetylated proteins and acetylated sites between CRC primary and distant metastatic tumor remains unclear. Our aim was to construct a complete atlas of acetylome in CRC and paired liver metastases. Combining high affinity enrichment of acetylated peptides with high sensitive mass spectrometry, we identified 603 acetylation sites from 316 proteins, among which 462 acetylation sites corresponding to 243 proteins were quantified. We further classified them into groups according to cell component, molecular function and biological process and analyzed the metabolic pathways, domain structures and protein interaction networks. Finally, we evaluated the differentially expressed lysine acetylation sites and revealed that 31 acetylated sites of 22 proteins were downregulated in CRC liver metastases compared to that in primary CRC while 40 acetylated sites of 32 proteins were upregulated, of which HIST2H3AK19Ac and H2BLK121Ac were the acetylated histones most changed, while TPM2 K152Ac and ADH1B K331Ac were the acetylated non-histones most altered. These results provide an expanded understanding of acetylome in CRC and its distant metastasis, and might prove applicable in the molecular targeted therapy of metastatic CRC. Biological significance: This study described provides, for the first time, that full-scale profiling of lysine acetylated proteins were identified and quantified in colorectal cancer (CRC) and paired liver metastases. The novelty of the study is that we constructed a complete atlas of acetylome in CRC and paired liver metastases. Moreover, we analyzed these differentially expressed acetylated proteins in cell component, molecular function and biological process. In addition, metabolic pathways, domain structures and protein interaction networks of acetylated proteins were also investigated. Our approaches shows that of the differentially expressed proteins, HIST2H3AK19Ac and H2BLK121Ac were the acetylated histones most changed, while TPM2 K152Ac and ADH1B K331Ac were the acetylated non-histones most altered. Our findings provide an expanded understanding of acetylome in CRC and its distant metastasis, and might prove applicable in the molecular targeted therapy of metastatic CRC. (C) 2016 Elsevier B.V. All rights reserved.Peer reviewe

Prognostic Biomarker SPOCD1 and Its Correlation with Immune Infiltrates in Colorectal Cancer

The biological role of the spen paralogue and orthologue C-terminal domain containing 1 (SPOCD1) has been investigated in human malignancies, but its function in colorectal cancer (CRC) is unclear. This study investigated the association between SPOCD1 expression and clinicopathological features of CRC cases, as well as its prognostic value and biological function based on large-scale databases and clinical samples. The results showed that the expression level of SPOCD1 was elevated in CRC, which was generally associated with shortened survival time and poor clinical indexes, including advanced T, N, and pathologic stages. Multivariate Cox regression analysis showed that elevated SPOCD1 expression was an independent factor for poor prognosis in CRC patients. Functional enrichment analysis of SPOCD1 and its co-expressed genes revealed that SPOCD1 could act as an oncogene by regulating gene expression in essential functions and pathways of tumorigenesis, such as extracellular matrix organization, chemokine signaling pathways, and calcium signaling pathways. In addition, immune cell infiltration results showed that SPOCD1 expression was associated with various immune cells, especially macrophages. Furthermore, our findings suggested a possible function for SPOCD1 in the polarization of macrophages from M1 to M2 in CRC. In conclusion, SPOCD1 is a promising diagnostic and prognostic marker for CRC, opening new avenues for research and treatment