Colorectal cancer (CRC) is one of the most common malignant tumors, with the second-highest mortality of all 36 cancers worldwide. The roles of fatty acid metabolism in CRC were investigated to explore potential therapeutic strategies. The data files were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to construct a prognostic risk score model with fatty acid metabolism-related genes for predicting prognosis in CRC. Patients with a high-risk score had a poorer prognosis in TCGA cohort than those with a low-risk score and were confirmed in the GEO cohort. Further analysis using the “pRRophetic” R package revealed that low-risk patients were more sensitive to 5-fluorouracil. A comprehensive evaluation of the association between prognostic risk score model and tumor microenvironment (TME) characteristics showed that high-risk patients were suitable for activating a type I/II interferon (IFN) response and inflammation-promoting function. Tumor Immune Dysfunction and Exclusion (TIDE) and SubMap algorithm results also demonstrated that high-risk patients are more suitable for anti-CTLA4 immunotherapy. Therefore, the evaluation of the fatty acid metabolism pattern promotes our comprehension of TME infiltration characteristics, thus guiding effective immunotherapy regimens.

Background: Accumulating evidence demonstrated immune/inflammation‐related implications of basophils in affecting tissue microenvironment that surrounded a tumor, and this study aimed to elucidate the clinical value of serum basophil count level.Methods: Between December 2007 and September 2013, 1029 patients diagnosed with stage I–III CRC in Fudan University Shanghai Cancer Center meeting the essential criteria were identified. The Kaplan–Meier method was used to construct the survival curves. Several Cox proportional hazard models were constructed to assess the prognostic factors. A simple predictor (CB classifier) was generated by combining serum basophil count and serum carcinoembryonic antigen (CEA) level which had long been accepted as the most important and reliable prognostic factor in CRC.Results: The preoperative basophils count < 0.025*10⁹/L was strongly associated with higher T stage, higher N stage, venous invasion, perineural invasion, elevated serum CEA level, and thus poor survival (P < 0.05). Moreover, multivariate Cox analysis showed that patients with low level of preoperative basophils count had an evidently poorer DFS [Hazard ratio (HR) = 2.197, 95% CI 1.868–2.585].Conclusions: As a common immune/inflammation‐related biomarker available from the blood routine examination, low level of preoperative serum basophil count was associated with aggressive biology and indicated evidently poor survival. Preoperative serum basophil count would be a useful and simple marker for the management of CRC patients.

Aim: This study aimed to investigate circumferential resection margin (CRM) as a prognostic factor for long‐term oncologic survival after rectal cancer surgery.Methods: Patients diagnosed with malignant rectal cancer between 1 January 2010 and 31 December 2014, from the Surveillance, Epidemiology, and End Results (SEER) program were identified for this study. The patients were divided into five CRM groups to compare the baseline characteristics and assess cancer‐specific survival (CSS): 0‐1 mm, 1.1‐2.0 mm, 2.1‐5.0 mm, 5.1‐10.0 mm, and >10 mm. The main endpoint was CSS.Results: Circumferential resection margin ≤1 mm was independently associated with 99% increased risk of cancer‐specific mortality in rectal cancer [hazard ratio (HR) = 1.990, 95% confidence interval (CI) = 1.613‐2.454, P < 0.001, using CRM (1.1‐2.0 mm) as a reference]. CRM (5.1‐10.0 mm) was independently associated with 29.2% decreased risk of cancer‐specific mortality [HR = 0.708, 95% CI = 0.525‐0.954, P = 0.152, using group (2.1‐5.0 mm) as reference]. CRM ≤2 mm or ≤0.4 mm was not obviously associated with CSS.Conclusions: circumferential resection margin is an independent prognostic factor in rectal cancer. Surgeons should try to maximize the CRM. Rectal cancer patients with CRM ≤1 mm should receive more postoperative attention depending on individual situation. Also, CRM should be accurately measured in millimeters in a preoperative magnetic resonance imaging or pathological report, rather than simply described as “involved” or “clear.”

Aim: This study focused on improving the American Joint Committee on Cancer TNM staging system and demonstrated an improvement in prognostic accuracy and clinical management of colon cancer using the P–TNM staging system. Patients and methods: Eligible patients (N=56,800) were identified from the Surveillance, Epidemiology, and End Results database between January 1, 2010, and December 31, 2014. The P-stage (P0 or P1) was assigned to each patient based on age at diagnosis, tumor grade, and tumor size. The outcome of interest was cancer-specific survival (CSS). The Cox proportional hazards regression analyses were used to identify independent prognostic factors and analyze the CSS probabilities of patients with colon cancer having different P–TNM stages, respectively. Results: A total of 29,627 patients were assigned to P0-stage and 27,173 patients were assigned to P1-stage. The P1-stage was associated with a 98.1% increased risk of cancer-specific mortality (hazard ratio =1.981, 95% confidence interval =1.891–2.076, P<0.001), which was higher in patients with nonmetastatic colon cancer. The P1-stage patients had improvement in CSS compared with those in P0-stage in respective stages (P<0.001). Moreover, CSS decreased in stage I–P1 compared with stage IIA–P0 or IIIA–P0 (P<0.001), stage IIIA–P1 compared with stage IIA–P0 (P<0.001), stage IIB–P1 compared with stage IIIB–P0 or IIC–P0 (P<0.001), stage IIIB–P1 compared with stage IIC–P0 (P<0.001), and stage IIC–P1 compared with stage IIIC–P0 (P<0.001). Conclusion: P-stage was an independent prognostic factor for colon cancer. This study strongly supported the incorporation of P-stage into the American Joint Committee on Cancer TNM staging system for a better approach to prognostication and, thus, more individualized risk-adaptive therapies in colon cancer.

Klotho (KL) was originally characterized as an aging suppressor gene, and has been identified as a tumor suppressor gene in a variety of cancers, including colorectal cancer. Recent years have witnessed the importance of metabolism transformation in cancer cell malignancies maintenance. Aberrant cancer cell metabolism is considered to be the hallmark of cancer. Our previous studies demonstrated that KL played negative roles in colon cancer cell proliferation and metastasis. However, its role in the cancer cell reprogramming has seldom been reported. The aim of this study was to examine the role of KL in aerobic glycolysis in colorectal cancer. Combining maximum standardized uptake value (SUVmax), which was obtained preoperatively via a PET/CT scan, with immunohistochemistry staining, we analyzed the correlation between SUVmax and KL expression in colorectal cancer tissues. The impact of KL on glucose metabolism and its mechanisms were further validated in vitro and in vivo. Patients with lower KL expression exhibited higher 18F-FDG uptake (P < 0.05), indicating that KL might participate in aerobic glycolysis regulation. In vitro assay by using colon cancer cell lines further supported this observation. By overexpressing KL in HTC116 and SW480 cells, we observed that the glycolysis was inhibited and the mitochondrial respiration increased, indicating that KL was a negative regulator of aerobic glycolysis. To seek for the underlying mechanisms, we tried to dig out the relation between KL and HIF1α signaling pathway, and found that KL negatively regulated HIF1α protein level and transcriptional activity. Western blot analysis showed that KL overexpression negatively regulated ERK pathway, and KL regulated aerobic glycolysis in part through its regulation of ERK/ HIF1α axis. Taken together, KL is a negative regulator of aerobic glycolysis and KL inhibited glucose metabolism transformation via the ERK/ HIF1α axis.