Objective: To propose modifications to refine prognostication over anatomic extent of the current tumor, node, and metastasis (TNM) staging system of non-small cell lung cancer (NSCLC) for a better distinction, and reflect survival differences of lung adenocarcinoma and squamous cell carcinoma. Study Design: Three large cohorts were included in this study. The training cohort consisted of 124,788 patients in the Surveillance, Epidemiology, and End Results (SEER) database (2006-2015). The validation cohort consisted of 4,247 patients from the Zhongshan Hospital, Fudan University (FDZSH; 2005-2014), and People's Hospital, Peking University (PKUPH; 2000-2017). The algorithm generated a hierarchical clustering model based on the unsupervised learning for survival data using Kaplan-Meier curves and log-rank test statistics for recursive partitioning and selection of the principal groupings. Results: In the modified staging system, adenocarcinoma cases are usually at a lower stage than the squamous cell carcinoma cases of the same TNM, reflecting a better outcome of adenocarcinoma than that of squamous cell carcinoma. The C-index of the modified staging system was significantly superior to that of the staging system [SEER cohort: 0.722, 95% CI, (0.721-0.723) vs. 0.643, 95% CI, (0.640-0.647); FDZSH cohort: 0.720, 95% CI, (0.709-0.731) vs. 0.519, 95% CI, (0.450-0.586); and PKUPH cohort: 0.730, 95% CI, (0.705-0.735) vs. 0.728, 95% CI, (0.703-0.753)]. Conclusion: Survival differences between lung adenocarcinoma and squamous cell carcinoma have been reflected accurately and reliably in the modified staging system based on the machine learning. It may refine prognostication over anatomic extent.

As is well known that colorectal cancer is the third most common cancer in the world, and radiation treatment plays a vital role in colorectal cancer therapy, but radiation resistance is a significant problem in the treatment of colorectal cancer. As an important member of the non-coding RNA family, long non-coding RNAs (lncRNAs) have been found that it plays a role in the occurrence and progression of colorectal cancer in recent years. However, little is known about the effect of lncRNA on colorectal cancer sensitivity to radiotherapy. We found that lnc-TLCD2-1 was significantly differentially expressed in radiation-tolerant CCL244 cell lines and radiation-sensitive HCT116 cell lines, suggesting that lnc-TLCD2-1 may regulate the radiosensitivity of colorectal cancer, and the relevant underlying mechanism was investigated. Cell clone formation assay, flow cytometry, and cell counting kit 8 (CCK8) were used to detect radiation sensitivity, apoptosis, and proliferation of colorectal cancer cells, respectively; Quantitative real-time PCR and western blot were used to detect the expression of genes; the direct interaction between lnc-TLCD2-1 and hsa-miR-193a-5p was verified by dual luciferase reporter assays; GEPIA, Starbase, TIMER and DAVID were used to complete expression of lnc-TLCD2-1, miR-193a-5p,YY1 and NF-кB-P65 in colorectal cancer, correlation, immune cell infiltration, GO and KEGG enrichment analysis. Clinical prognostic analysis data were obtained from GSE17536 dataset. After radiotherapy for HCT116, the expression of lnc-TLCD2-1 was increased, and the expression of hsa-miR-193a-5p was significantly decreased, while that of CCL244 was the opposite, and the change range of lnc-TLCD2-1 was relatively small. HCT116 with overexpression of lnc-TLCD2-1 after radiation treatment, the number of cell colonies significantly increased, and cell apoptosis decreased compared with the negative control group. The cell colonies and apoptosis of CCL244 with disturbed expression of lnc-TLCD2-1 were opposite to those of HCT116. Lnc-TLCD2-1 can regulate the expression of YY1/NF-кB-P65 by targeting miR-193a-5p. Lnc-TLCD2-1 can promote the proliferation of colorectal cancer. High expression of lnc-TLCD2-1 independently predicted a shorter survival. Lnc-TLCD2-1 is associated with radiation resistance and short survival in colorectal cancer patients. In addition, Lnc-TLCD2-1 can promote the proliferation of colorectal cancer. Our study provides a scientific basis for targeting lnc-TLCD2-1 in colorectal cancer radiation resistance interventions and selection of prognostic biomarker.