Serum tumor marker and CT body composition scoring system predicts outcomes in colorectal cancer surgical patients.

OBJECTIVE: To investigate the prognostic value of preoperative body composition and serum tumor markers (STM) in patients undergoing surgical treatment for colorectal cancer (CRC) and to establish the prognostic score for patients with CRC. METHODS: This study enrolled 365 patients (training set 245, validation set 120) with CRC who underwent surgical resection. The predictive value of various body composition features and STM for determining CRC prognosis were compared. A novel index score based on the independent risk factors from Cox regression for CRC patients was established and evaluated for its usefulness. RESULTS: Multivariate Cox regression showed that low skeletal muscle radiodensity (SMD) (p = 0.020), low subcutaneous fat area (SFA) (p = 0.029), high carcinoembryonic antigen (CEA) (p = 0.008), and high alpha-fetoprotein (AFP) (p = 0.039) were all independent prognostic factors for poor overall survival (OS). The multifactorial analysis indicated that high intermuscular fat area (IMFA) (p = 0.033) and high CEA (p = 0.009) were independent prognostic factors for poor disease-free survival (DFS). Based on these findings, two scoring systems for OS and DFS were established in the training datasets. CRC patients who scored higher on the new scoring systems had lower OS and DFS (both p < 0.001) as shown in the Kaplan-Meier survival curves in the training and validation datasets. CONCLUSION: In predicting the prognosis of CRC patients, SFA and SMD are superior to other body composition measurements. A scoring system based on body composition and STM can have prognostic value and clinical applicability. CLINICAL RELEVANCE STATEMENT: This scoring system, combining body composition and serum tumor markers, may help predict postoperative survival of CRC patients and help clinicians make well-informed decisions regarding the treatment of patients. KEY POINTS: Colorectal cancer prognosis can be related to body composition. High intermuscular fat area and CEA were independent prognostic factors for poor disease-free survival. This scoring system, based on body composition and tumor markers, can prognosticate for colorectal cancer patients.

Perineural invasion affects prognosis of patients undergoing colorectal cancer surgery: a propensity score matching analysis.

BACKGROUND: Tumour perineural invasion (PNI) is a predictor of poor prognosis, but its effect on the prognosis of patients with colorectal cancer (CRC) has not yet been elucidated. METHODS: This retrospective study used propensity score matching (PSM). The clinical case data of 1470 patients with surgically treated stage I-IV CRC at Wuhan Union Hospital were collected. PSM was used to analyse and compare the clinicopathological characteristics, perioperative outcomes, and long-term prognostic outcomes of the PNI(+) and PNI(-) groups. The factors influencing prognosis were screened using Cox univariate and multivariate analyses. RESULTS: After PSM, 548 patients were included in the study (n = 274 in each group). Multifactorial analysis showed that neurological invasion was an independent prognostic factor affecting patients' OS and DFS (hazard ratio [HR], 1.881; 95% confidence interval [CI], 1.35-2.62; P = 0.0001; HR, 1.809; 95% CI, 1.353-2.419; P < 0.001). Compared to PNI(+) patients without chemotherapy, those who received chemotherapy had a significant improvement in OS (P < 0.01). The AUROC curve of OS in the PNI(+) subgroup (0.802) was higher than that after PSM (0.743), while that of DFS in the PNI(+) subgroup (0.746) was higher than that after PSM (0.706). The independent predictors of PNI(+) could better predict the prognosis and survival of patients with PNI(+). CONCLUSIONS: PNI significantly affects the long-term survival and prognosis of patients with CRC undergoing surgery and is an independent risk factor for OS and DFS in patients with CRC undergoing surgery. Postoperative chemotherapy significantly improved the OS of PNI(+) patients.

Influence of skeletal muscle and intermuscular fat on postoperative complications and long-term survival in rectal cancer patients.

BACKGROUND: The body composition of patients with rectal cancer potentially affects postoperative outcomes. This study explored the correlations between skeletal muscle and adipose tissue quantified by computed tomography (CT) with postoperative complications and long-term prognosis in patients with rectal cancer after surgical resection. METHODS: This retrospective cohort study included patients with rectal cancer who underwent surgical resection at the Wuhan Union Hospital between 2014 and 2018. CT images within 3 months prior to the surgery were used to quantify the indices of skeletal muscle and adipose tissue at the levels of the third lumbar vertebra (L3) and umbilicus. Optimal cut-off values for each index were defined separately for males and females. Associations between body composition and postoperative complications, overall survival (OS), and disease-free survival (DFS) were evaluated using logistic and Cox proportional hazards models. RESULTS: We included 415 patients (240 males and 175 females; mean age: 57.8 ± 10.5 years). At the L3 level, a high skeletal muscle density (SMD; hazard ratio [HR]: 0.357, 95% confidence interval [CI]: 0.191-0.665, P = 0.001; HR: 0.571, 95% CI: 0.329-0.993, P = 0.047) and a high skeletal muscle index (SMI; HR: 0.435, 95% CI 0.254-0.747, P = 0.003; HR: 0.568, 95% CI: 0.359-0.897, P = 0.015) were independent prognostic factors for better OS and DFS. At the umbilical level, a large intermuscular fat area (IMFA; HR: 1.904, 95% CI: 1.068-3.395, P = 0.029; HR: 2.064, 95% CI: 1.299-3.280, P = 0.002) was an independent predictive factor for worse OS and DFS, and a high SMI (HR: 0.261, 95% CI: 0.132-0.517, P < 0.001; HR: 0.595, 95% CI: 0.387-0.913, P = 0.018) was an independent prognostic factor for better OS and DFS. The models combining body composition and clinical indicators had good predictive abilities for OS. The receiver operating characteristic areas under the curve were 0.848 and 0.860 at the L3 and umbilical levels, respectively (both P < 0.05). CONCLUSIONS: No correlations existed between CT-quantified body composition parameters and postoperative complications. However, a high SMD and high SMI were significantly associated with longer OS and DFS at the L3 level, whereas a large IMFA and low SMI were associated with worse OS and DFS at the umbilical level. Combining CT-quantified body composition and clinical indicators could help physicians predict the prognosis of patients with rectal cancer after surgery.

Fumarate Hydratase Enhances the Therapeutic Effect of PD-1 Antibody in Colorectal Cancer by Regulating PCSK9.

Despite the notable achievements of programmed death 1 (PD-1) antibodies in treating various cancers, the overall efficacy remains limited in the majority of colorectal cancer (CRC) cases. Metabolism reprogramming of tumors inhibits the tricarboxylic acid (TCA) cycle, leading to down-regulation of fumarate hydratase (FH), which is related to poor prognosis in CRC patients. By establishing a tumor-bearing mouse model of CRC with Fh1 expression deficiency, we confirmed that the therapeutic effect of PD-1 antibodies alone was suboptimal in mice with low Fh1 expression, which was improved by combination with a protein invertase subtilisin/kexin 9 (PCSK9) inhibitor. Mechanistically, FH binds to Ras-related nucleoprotein (RAN), which inhibits the nuclear import of the PCSK9 transcription factor SREBF1/2, thus reducing the expression of PCSK9. This leads to increased clonal expansion of CD8+ T cells while the number of Tregs remains unchanged, and the expression of PD-L1 does not change significantly, thus enhancing the immunotherapy response. On the contrary, the expression of PCSK9 increased in CRC cells with low FH expression, which antagonized the effects of immunotherapy. Overall, CRC patients with low FH expression may benefit from combinatorial therapy with PD-1 antibodies and PCSK9 inhibitors to enhance the curative effect.