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Impact of negative lymph nodes on colon cancer survival and exploring relevant transcriptomics differences through real-world data analyses.

ABSTRACT: Background:The prognostic role and underlying heterogeneity of negative lymph nodes (NLNs) on colon cancer is not well understood. The purpose of this study was to construct NLN-based prognostic models and reveal relevant mechanisms affecting NLNs by analyzing omic data. Methods:This inception cohort study included 314,398 colon cancer patients from the US Surveillance, Epidemiology, and End Results (SEER) database. Receiver operating characteristic (ROC) curve was used to determine the cut-off of NLNs. Nomograms were constructed and validated using SEER data and the Cancer Genome Atlas (TCGA) data, respectively. The differentially expressed genes (DEGs) were analyzed using edgeR. Enrichment analyses were performed by Metascape. Results:Multivariate analysis confirmed the high NLN had improved cancer-specific survival (CSS) and overall survival (OS) compared to low NLN [hazard ratio (HR) =0.610, 95% confidence interval (CI), 0.601-0.620] for CSS and (HR =0. 682, 95% CI, 0.674-0.690) for OS. Nomograms were established for CSS and OS with the c-statistic 0.790 (95% CI, 0.788-0.792) for CSS and 0.734 (95% CI, 0.732-0.736) for OS. High NLN was associated with less B cell (P=0.002) and macrophage infiltration (P<0.0001), high microsatellite instability (MSI) (OR =4.325, P=0.001), and hypermutation (OR =4.285, P=0.001; high vs. low). Transcriptomics analysis demonstrated histone modifiers were the most significant different biological processes between the high and low NLN group. Conclusions:The NLN-based models can aid in personalized risk stratification for colon cancer. This study postulates that high NLN may represent a biological subtype with less macrophage infiltration, high MSI status, hypermutation, and histone modifier gene enriched expression, and thus warrants further investigation.

SUBMITTER: Hao Y

PROVIDER: S-EPMC6861746 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Impact of negative lymph nodes on colon cancer survival and exploring relevant transcriptomics differences through real-world data analyses.

Hao Yuying Y Zhang Jiandong J Du Rui R Huang Xinyi X Li Hui H Hu Pingping P

Annals of translational medicine 20191001 20

<h4>Background</h4>The prognostic role and underlying heterogeneity of negative lymph nodes (NLNs) on colon cancer is not well understood. The purpose of this study was to construct NLN-based prognostic models and reveal relevant mechanisms affecting NLNs by analyzing omic data.<h4>Methods</h4>This inception cohort study included 314,398 colon cancer patients from the US Surveillance, Epidemiology, and End Results (SEER) database. Receiver operating characteristic (ROC) curve was used to determi ...[more]

PMID: 31807507

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Project description:BACKGROUND:Globally, colorectal cancer (CRC) is the third and second leading cancer in men and women respectively with 600,000 deaths per year. Traditionally, clinicians have relied solely on nodal disease involvement, and measurements such as lymph node ratio (LNR; the ratio of metastatic/positive lymph nodes to total number of lymph nodes examined), when determining patient prognosis in CRC. The log odds of positive lymph nodes (LODDS) is a logistic transformation formula that uses pathologic lymph node data to stratify survival differences among patients within a single stage of disease. This formula allows clinicians to identify whether patients with clinically aggressive tumours fall into higher-risk groups regardless of nodal positivity and can potentially guide adjuvant treatment modalities. The aim of this study was to investigate whether LODDS in colon cancer provides better prognostication compared to LNR. METHODS:A retrospective study of patients on the prospectively maintained Cabrini Monash University Department of Surgery colorectal neoplasia database, incorporating data from hospitals in Melbourne Australia, identified patients entered between January 2010 and March 2016. Association of LODDS and LNR with clinical variables were analysed. Disease-free (DFS) and overall (OS) survival were investigated with Cox regression and Kaplan-Meier survival analyses. RESULTS:There were 862 treatment episodes identified in the database (402 male, 47%). The median patient age was 73 (range 22-100?years). There were 799 colonic cancers and 63 rectosigmoid cancers. The lymph node yield (LNY) was suboptimal (<?12) in 168 patients (19.5%) (p?=?0.05). The 5-year OS for the different LNR groups were 86, 91 and 61% (p?<?0.001) for LNR0 (655 episodes), LNR1 (128 episodes) and LNR2 (78 episodes), respectively. For LODDS, they were 85, 91 and 61% (p?<?0.001) in LODDS0 (569 episodes), LODDS1 (217 episodes) and LODDS2 (75 episodes) groups (p?<?0.001). Overall survival rates were comparable between the LNR and LODDS group and for LNY?<?12 and stage III patients when each were sub-grouped by LODDS and LNR. CONCLUSION:This study has shown for that the prognostic impact of LODDS is comparable to LNR for colon cancer patients. Accordingly, LNR is recommended for prognostication given its ease of calculation.

Dataset Information

Impact of negative lymph nodes on colon cancer survival and exploring relevant transcriptomics differences through real-world data analyses.

Publications

Impact of negative lymph nodes on colon cancer survival and exploring relevant transcriptomics differences through real-world data analyses.

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