Splenic flexure cancer shows poorer survival than descending colon cancer: an integrated Surveillance, Epidemiology, and End Results and The Cancer Genome Atlas analysis.

The survival differences between splenic flexure cancer (SFC) and descending colon cancer (DCC) are unclear owing to their distinct anatomic and molecular features. This study compares their survival outcomes and genetic differences using data from the Surveillance, Epidemiology, and End Results (SEER) and The Cancer Genome Atlas (TCGA) databases. This study used SEER data (2000-2022) to compare postoperative patients with SFC and DCC. Propensity score matching (PSM) was performed to balance baseline characteristics. Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan-Meier method, and competing-risk analysis with a multivariable Fine-Gray model was used to evaluate cancer-specific death (CSD). TCGA transcriptomic data were analyzed to identify differentially expressed genes and enriched pathways between SFC and DCC. A total of 7579 patients were identified from SEER, including 2636 with SFC and 4943 with DCC. After PSM, DCC remained associated with significantly better OS and CSS than SFC. Competing-risk analysis showed that SFC had higher cumulative incidences of both CSD and other-cause death, and multivariable Fine-Gray analysis further demonstrated that DCC was independently associated with a lower risk of CSD than SFC (subdistribution hazard ratio, 0.73; P =.019). Younger age and adequate nodal evaluation were protective, whereas advanced tumor burden, particularly T4 and N2 disease, remained strongly adverse. TCGA analysis further demonstrated distinct transcriptional profiles between the 2 subsites, with SNHG4 upregulated and AHCYL2 downregulated in SFC, alongside subsite-associated differences in fatty-acid metabolism, spliceosome-related signaling, and ribosome-associated processes. SFC is associated with worse survival than DCC, and transcriptomic profiles are distinct between the 2 subsites in TCGA.