No abstract

PurposeInterleukin-6 (IL-6) plays an important role in human colorectal cancer (CRC) development. However, the exact clinical and prognostic significance of IL-6 in CRC is still unclear. Here, we conducted this meta-analysis to explore this issue in detail.MethodsA meta-analysis was performed to clarify the association between serum IL-6 expression and clinical outcomes in articles published up to June 2015. Weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) were used to assess the association between serum IL-6 expression and the clinicopathological characteristics of CRC. Hazard ratio (HR) with 95% CI was used to quantify the predictive value of IL-6 on CRC prognosis.ResultsFourteen studies comprising 1,245 patients were included. Analysis of these data showed that serum IL-6 expression was highly correlated with poor 5-year overall survival (OS) rate (HR =0.43, 95% CI: 0.31–0.59, P=0.755). Simultaneously, we also found that serum IL-6 expression was associated with certain clinical parameters of CRC, such as tumor invasion (T category: T0–T2, T3–T4) (WMD =3.15, 95% CI: 1.92–4.39, P=0.816), distant metastasis (M category: M0, M1) (WMD =4.69, 95% CI: 3.33–6.06, P=0.377), and tumor stage (I–II, III–IV) (WMD =2.65, 95% CI: 1.09–4.21, P=0.066).ConclusionA high serum IL-6 expression is associated with adverse OS in CRC. The IL-6 expression can be an important supplement in establishing prognostic score for clinical decision.

Background: Tumor progression and distant metastasis are the main causes of deaths in colorectal cancer (CRC) patients, and the molecular mechanisms in CRC metastasis have not been completely discovered. Methods: We identified differentially expressed genes (DEGs) and lncRNAs (DELs) of CRC from The Cancer Genome Atlas (TCGA) database. Then we conducted the weighted gene co-expression network analysis (WGCNA) to investigate co-expression modules related with CRC metastasis. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, DEG-DEL co-expression network and survival analyses of significant modules were also conducted. Finally, the expressions of selected biomarkers were validated in cell lines by quantitative real-time PCR (qRT-PCR). Results: 2032 DEGs and 487 DELs were involved the construction of WGCNA network, and greenyellow, turquoise and brown module were identified to have more significant correlation with CRC metastasis. GO and KEGG pathway analysis of these three modules have proven that the functions of DEGs were closely involved in many important processes in cancer pathogenesis. Through the DEG-DEL co-expression network, 12 DEGs and 2 DELs were considered as hub nodes. Besides, survival analysis showed that 30 DEGs were associated with the overall survival of CRC. Then 10 candidate biomarkers were chosen for validation and the expression of CA2, CHP2, SULT1B1, MOGAT2 and C1orf115 were significantly decreased in CRC cell lines when compared to normal human colonic epithelial cells, which were consistent with the results of differential expression analysis. Especially, low expression of SULT1B1, MOGAT2 and C1orf115 were closely correlated with poorer survival of CRC. Conclusion: This study identified 5 genes as new biomarkers affecting the metastasis of CRC. Besides, SULT1B1, MOGAT2 and C1orf115 might be implicated in the prognosis of CRC patients.

Background. Immune checkpoint inhibitors (ICIs) have rapidly revolutionized colorectal cancer (CRC) treatment, but resistance caused by the heterogeneous tumor microenvironment (TME) still presents a challenge. Therefore, it is necessary to characterize TME immune infiltration and explore new targets to improve immunotherapy. Methods. The compositions of 64 types of infiltrating immune cells and their relationships with CRC patient clinical characteristics were assessed. Differentially expressed genes (DEGs) between “hot” and “cold” tumors were used for functional analysis. A prediction model was constructed to explore the survival of CRC patients treated with and without immunotherapy. Finally, fatty acid-binding protein (FABP6) was selected for in vitro experiments, which revealed its roles in the proliferation, apoptosis, migration, and immunogenicity of CRC tissues and cell lines. Results. The infiltration levels of several immune cells were associated with CRC tumor stage and prognosis. Different cell types showed the synergistic or antagonism infiltration patterns. Enrichment analysis of DEGs revealed that immune-related signaling was significantly activated in hot tumors, while metabolic process pathways were altered in cold tumors. In addition, the constructed model effectively predicted the survival of CRC patients treated with and without immunotherapy. FABP6 knockdown did not significantly alter tumor cell proliferation, apoptosis, and migration. FABP6 was negatively correlated with immune infiltration, and knockdown of FABP6 increased major histocompatibility complex (MHC) class 1 expression and promoted immune-related chemokine secretion, indicating the immunogenicity enhancement of tumor cells. Finally, knockdown of FABP6 could promote the recruitment of CD8+ T cells. Conclusion. Collectively, we described the landscape of immune infiltration in CRC and identified FABP6 as a potential immunotherapeutic target for treatment.

No abstract