Systemic Inflammatory Markers of Resectable Colorectal Cancer Patients with Different Mismatch Repair Gene Status

Abstract

Background

We aimed to assess the differences in gene expression and systemic inflammatory markers in colorectal cancer (CRC) patients with different mismatch repair (MMR) statuses.

Methods

Bioinformatics analysis was used to identify the different expression genes in patients with CRC at different MMR statuses. A total of 208 patients with resectable colorectal cancer, including 104 deficient mismatch repair (dMMR) patients and 104 matched proficient mismatch repair (pMMR) patients, were retrospectively analyzed.

Results

Bioinformatics analysis showed that chemokine-mediated signaling pathway and inflammatory responses were the main differences in gene expression between dMMR and pMMR CRC patients. In all 208 patients with CRC, those with dMMR frequently had it located on the right side, with more mucinous adenocarcinoma and grade 3 tumors. Patients with dMMR had an earlier American Joint Committee on Cancer (AJCC) stage than pMMR patients. Meanwhile, lymph nodes (LNs) metastasis was more frequently negative in dMMR patients than pMMR patients. Interestingly, patients with CRC with dMMR had more regional lymph nodes removed during surgery, although with less metastatic cancer. Patients with resectable CRC with dMMR were more likely to have higher levels of neutrophil, monocyte, platelet, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), C-reactive protein to albumin ratio (CAR), Glasgow prognostic score (GPS) and C-reactive protein (CRP). In patients with dMMR, those with higher levels of PLR, MLR, CAR, and co-effect present had shorter overall survival (OS) significantly. It was noteworthy that the prognosis of high levels of systemic inflammatory markers did not predict prolonged OS in patients with pMMR CRC.

Conclusion

dMMR CRC has presented a comprehensively distinct systemic inflammatory microenvironment. The systemic inflammatory response can predict oncological outcomes in patients with CRC with dMMR.

Keywords:

• gene expression
• systemic inflammatory markers
• colorectal cancer
• bioinformatics analysis
• lymph nodes

Acknowledgments

We are grateful to all clinical investigators and the included patients.

Abbreviations

ICBM, Institute of Cancer and Basic Medicine; LNs, lymph node; CRC, Colorectal cancer; CIN, chromosomal instability; MSI, microsatellite instability; HNPCC, hereditary nonpolyposis colorectal cancer; SCRC, sporadic colorectal cancer; MMR, Mismatched repair; PD-1, programmed cell death 1; NCBI, National Center for Biotechnology Information; GO, gene ontology; AJCC, American Joint Committee on Cancer; CRP, C-reactive protein; LDH, lactic dehydrogenase; IHC, immunohistochemical; DAB, diaminobenzidine; DEG, differential expression genes; OS, overall survival; HI, high inflammation; LI, low inflammation.

Ethics Approval and Consent to Participate

The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of IRB-2020-239(Ke).

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no potential conflicts of interest.