Dataset Information

Comprehensive analysis of lymph nodes metastasis associated genes in cervical cancer and its significance in treatment and prognosis

ABSTRACT:

Background

Cervical carcinoma is one of the most common malignant tumors of the female reproductive system. Lymph nodes metastasis, the most common metastasis, which can be detected even in small-size tumor patients, results in worse prognosis. Therefore, it is of great significance to explore novel lymph nodes metastasis associated biomarkers, which can predict the prognosis and provide a good reference for clinical decision making in cervical carcinoma patients. However, systematic and comprehensive studies related to the key molecules in lymph node metastasis in cervical carcinoma patients are still absent.

Methods

Transcriptome and clinical data of 307 cervical carcinoma patients were obtained from The Cancer Genome Atlas (TCGA). Then, survival of patients with and without lymph node metastasis was analyzed by Kaplan-Meier (K-M) curves. Differential expressed genes (DEGs) were detected between tumor and control samples using limma package and defined as lymph node metastasis related genes. Univariate and multivariate Cox regression analyses were carried out to screen robust prognostic gene signature. The risk score model and nomogram for predicting survival were constructed based on prognostic gene signature. The performance of the risk score model was evaluated by operating characteristic (ROC) curves. Based on risk score, patients were divided into low- and high- risk groups. DEGs, functional enrichment analysis and tumor microenvironment (immune infiltration and expressions of immune checkpoints) were detected in low- and high-risk groups.

Results

A total of 103 lymph node metastasis-associated genes were identified. Univariate and multivariate Cox regression analyses identified TEKT2, LPIN2, FABP4 and CXCL2 as prognostic gene signature. The risk score model was constructed and validated in cervical carcinoma patients. 345 DEGs identified between high- and low-risk groups were significantly enriched into immune-related biological processes. Furthermore, we found that the immune infiltration and expressions of immune checkpoints were significantly different between low- and high-risk groups.

Conclusion

Our study revealed that lymph node metastasis played an important role in the prognosis of cervical carcinoma patients. Furthermore, we established a risk score model based on lymph node metastasis related genes, which could accurately predict the survival of cervical carcinoma patients. Besides, our findings in tumor microenvironments of low- and high-risk groups improved our understanding of the relationship between lymph node metastasis related genes and cervical carcinoma.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12885-021-08945-8.

SUBMITTER: Yang P

PROVIDER: S-EPMC8597253 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundLymph node metastasis in the cervical region posterior to level V (PLV) can occurs in patients with nasopharyngeal carcinoma (NPC), but the significance of lymph node metastasis in this region and the delineation of the radiotherapy target area have not been reported. We aimed to explore the distribution pattern and prognosis of metastatic lymph nodes in the PLV region in patients with NPC.MethodsWe retrospectively studied 605 cases of NPC diagnosed by pathological detection from December 2011 to November 2017. The nodal distribution at each level was assessed in accordance with the Radiation Therapy Oncology Group (RTOG) guidelines proposed in 2013. The central points of the metastatic lymph nodes of the PLV region in the patients were recreated proportionally on the CT images of a standard patient with N0 NPC in reference to the normal anatomy of the PLV area. The correlation between the PLV region and the other levels, the nodal location, and the characteristics and prognosis of the PLV region were analyzed.ResultsLymph node metastasis occurred in 557 (92.06%) of 605 patients. There were 30 patients (4.95%) with lymph node metastasis in the PLV region. A total of 49 metastatic lymph nodes from the PLV region were counted, and the mean vertical distance of the central point of each lymph node from the anterior surface of the trapezius muscle was 14 mm. Linear regression correlation analysis suggested that lymph node metastasis in the PLV region was associated with ipsilateral level IVa (P = 0.018), level Va, level Vb, and level Vc lymph node metastasis (all P < 0.001). The 5-year OS, PFS, LRFS, and DMFS of 29 patients with lymph node metastasis in the PLV region were 41.6, 27.7, 89.1, and 47.3%, respectively. Multivariate analysis showed that lymph node metastasis in the PLV region was an independent prognostic factor for DMFS (P < 0.05).ConclusionNPC patients with lymph node metastasis in the PLV region had a poor prognosis and a high risk of distant metastasis. We recommend that the margin of the PLV region may be a new cervical lymph node segment for NPC.