Abstract

Simple SummaryCXCs are important genes that regulate inflammation and tumor metastasis. While there are many studies with a focus on individual CXCs, few present a pan-cancer analysis of the whole CXC family. Our results indicate that CXCs are a potential therapeutic target in a variety of tumors and a potential prognostic marker that could improve the survival of cancer patients and the accuracy of prognosis. Meanwhile, we found that CXCs may be involved in diseases caused by intestinal flora.Background: CXCs are important genes that regulate inflammation and tumor metastasis. However, the expression level, prognosis value, and immune infiltration of CXCs in cancers are not clear. Methods: Multiple online datasets were used to analyze the expression, prognosis, and immune regulation of CXCs in this study. Network analysis of the Amadis database and GEO dataset was used to analyze the regulation of intestinal flora on the expression of CXCs. A mouse model was used to verify the fact that intestinal bacterial dysregulation can affect the expression of CXCs. Results: In the three cancers, multiple datasets verified the fact that the mRNA expression of this family was significantly different; the mRNA levels of CXCL3, 8, 9, 10, 14, and 17 were significantly correlated with the prognosis of three cancers. CXCs were correlated with six types of immuno-infiltrating cells in three cancers. Immunohistochemistry of clinical samples confirmed that the expression of CXCL8 and 10 was higher in three cancer tissues. Animal experiments have shown that intestinal flora dysregulation can affect CXCL8 and 10 expressions. Conclusion: Our results further elucidate the function of CXCs in cancers and provide new insights into the prognosis and immune infiltration of breast, colon, and pancreatic cancers, and they suggest that intestinal flora may influence disease progression through CXCs.

Highlights

  • Cancer is a major worldwide public health problem, causing an estimated total of 9 million deaths in 2016 (World Health Statistics, 2020)

  • Our previous studies have shown that the protection of colorectal cancer cells from radiotherapy by CXCL12/CXCR4 is mediated by survivin in colorectal cancer [12]

  • We investigated the results of sequencing obtained after coculture of Fusobacterium nucleatum with colon cancer cell lines and determined that the expression of CXCL8 was significantly increased, and the expression of CXCL10 was decreased in the HT29 cell line cocultured with Fusobacterium nucleatum

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Summary

Introduction

Cancer is a major worldwide public health problem, causing an estimated total of 9 million deaths in 2016 (World Health Statistics, 2020). Tumor metastasis is an important factor that correlates with a poor prognosis of cancer. Network analysis of the Amadis database and GEO dataset was used to analyze the regulation of intestinal flora on the expression of CXCs. A mouse model was used to verify the fact that intestinal bacterial dysregulation can affect the expression of CXCs. Results: In the three cancers, multiple datasets verified the fact that the mRNA expression of this family was significantly different; the mRNA levels of CXCL3, 8, 9, 10, 14, and 17 were significantly correlated with the prognosis of three cancers. Conclusion: Our results further elucidate the function of CXCs in cancers and provide new insights into the prognosis and immune infiltration of breast, colon, and pancreatic cancers, and they suggest that intestinal flora may influence disease progression through CXCs

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