Combining pathological risk factors and T, N staging to optimize the assessment for risk stratification and prognostication in low-risk stage III colon cancer.

BACKGROUND: This study aimed to investigate the combined pathological risk factors (PRFs) to stratify low-risk (pT1-3N1) stage III colon cancer (CC), providing a basis for individualized treatment in the future. PATIENTS AND METHODS: PRFs for low-risk stage III CC were identified using COX model. Low-risk stage III CC was risk-grouped combining with PRFs, and survival analysis were performed using Kaplan-Meier. The Surveillance, Epidemiology, and End Results (SEER) databases was used for external validation. RESULTS: Nine hundred sixty-two stage III CC patients were included with 634 (65.9%) as low risk and 328 (34.1%) as high risk. Poor differentiation (OS: P = 0.048; DFS: P = 0.011), perineural invasion (OS: P = 0.003; DFS: P < 0.001) and tumor deposits (OS: P = 0.012; DFS: P = 0.003) were identified as PRFs. The prognosis of low-risk CC combined with 2 PRFs (OS: HR = 3.871, 95%CI, 2.004-7.479, P < 0.001; DFS: HR = 3.479, 95%CI, 2.158-5.610, P < 0.001) or 3 PRFs (OS: HR = 5.915, 95%CI, 1.953-17.420, P = 0.002; DFS: HR = 5.915, 95%CI, 2.623-13.335, P < 0.001) was similar to that of high-risk CC (OS: HR = 3.927, 95%CI, 2.317-6.656, P < 0.001; DFS: HR = 4.132, 95%CI, 2.858-5.974, P < 0.001). In the SEER database, 18,547 CC patients were enrolled with 10,023 (54.0%) as low risk and 8524 (46.0%) as high risk. Low-risk CC combined with 2 PRFs (OS: HR = 1.857, 95%CI, 1.613-2.139, P < 0.001) was similar to that of high-risk CC without PRFs (HR = 1.876, 95%CI, 1.731-2.033, P < 0.001). CONCLUSION: Combined PRFs improved the risk stratification of low-risk stage III CC, which could reduce the incidence of undertreatment and guide adjuvant chemotherapy.

Survival outcomes of different neoadjuvant treatment regimens in patients with locally advanced rectal cancer and MRI-detected extramural venous invasion.

PURPOSE: MRI-detected extramural venous invasion (mrEMVI) is associated with poor survival outcomes in patients with locally advanced rectal cancer (LARC). An mrEMVI-positive status is considered a strong indication for neoadjuvant treatment, but the optimal regimen is unknown. PATIENTS AND METHODS: We retrospectively compared pathological and survival outcomes of 584 patients diagnosed with mrEMVI-positive rectal cancer between January 2013 and October 2021, and receiving either neoadjuvant chemotherapy (NCT) alone, neoadjuvant chemoradiotherapy (nCRT) alone, or nCRT plus NCT, prior to total mesorectal excision. Propensity score matching (PSM) was used to balance clinical bias between groups, which were compared using chi-square testing and Kaplan-Meier curves. RESULTS: Median follow-up was 33.9 (range, 10.2-100.4) months. The 3-year overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS) rates for all patients were 90.4%, 57.5%, 61.1%, and 85.7%, respectively. Of 584 mrEMVI-positive patients at the time of diagnosis, 457 (78.3%) were EMVI-negative on surgical pathology, and they had significantly better 3-year OS, DMFS, DFS, and LRFS rates (all p < 0.001) than patients who remained EMVI-positive. After PSM was applied, patients receiving nCRT alone had significantly better 3-year OS (96.8% vs. 86.5%, p = 0.005) and DMFS (67.1% vs. 53.5%, p = 0.03) rates than those receiving NCT alone. Patients receiving NCT plus nCRT had higher pathological complete response (PCR) (10.8% vs. 2.7%, p = 0.04) and downstaging (33.8% vs. 5.3%, p < 0.001) rates than those receiving nCRT alone, but survival rates did not differ (all p > 0.05). CONCLUSION: Most EMVI-positive patients with LARC converted to EMVI-negative after neoadjuvant treatment, resulting in improved OS and DFS. Patients receiving nCRT had more favorable survival outcomes than those receiving NCT, suggesting the importance of including neoadjuvant radiotherapy. Patients receiving NCT in addition to nCRT had higher rates of PCR and downstaging, but their survival rates were not better.

Construction and Validation of a Novel Prognosis Model in Colon Cancer Based on Cuproptosis-Related Long Non-Coding RNAs.

Colon cancer (CC) is one of the most common (6%) malignancies and leading cause of cancer-associated death (more than 0.5 million) worldwide, which demands reliable prognostic biomarkers. Cuproptosis is a novel modality of regulated cell death triggered by the accumulation of intracellular copper. LncRNAs have been reported as prognostic signatures in different types of tumors. However, the correlation between cuproptosis-related lncRNAs (CRLs) and CC remains unclear. Data of CC patients were downloaded from public databases. The prognosis-associated CRLs were identified by co-expression analysis and univariate Cox. Least absolute shrinkage and selection operator were utilized to construct the CRLs-based prognostic signature in silico for CC patients. CRLs level was validated in human CC cell lines and patient tissues. ROC curve and Kaplan-Meier curve results revealed that high CRLs-risk score was associated with poor prognosis in CC patients. Moreover, the nomogram revealed that this model possessed a steady prognostic prediction capability with C-index as 0.68. More importantly, CC patients with high CRLs-risk score were more sensitive to eight targeted therapy drugs. The prognostic prediction power of the CRLs-risk score was further confirmed by cell lines, tissues and two independent CC cohorts. This study constructed a novel ten-CRLs-based prognosis model for CC patients. The CRLs-risk score is expected to serve as a promising prognostic biomarker and predict targeted therapy response in CC patients.

The effect of recombinant human epidermal growth factor on radiation dermatitis in rectal and anal cancer patients: a self-controlled study.

BACKGROUND: Our previous study reported that recombinant human epidermal growth factor (rhEGF)-triggered EGFR internalization promoted radioresistance. Here, we aimed to evaluate the effect of rhEGF on the skin protection of rectal and anal cancer patients receiving radiotherapy. METHODS: One hundred and ninety-three rectal and anal cancer patients who received radiotherapy were prospectively enrolled from January 2019 to December 2020. To perform self-controlled study, the left and right pelvic skin area (separated by midline) were randomly assigned to the rhEGF and control side. The association between radiation dermatitis and factors including rhEGF, the dose of radiotherapy and tumor distance from anal edge were analyzed. RESULTS: Among 193 enrolled patients, 41 patients (21.2%) did not develop radiation dermatitis, and 152 patients (78.8%) suffered radiation dermatitis on at least one side of pelvic skin at the end of radiotherapy. For the effect on radiation dermatitis grade, rhEGF had improved effect on 6 (4.0%) patients, detrimental effect on 2 (1.3%) patients, and no effect on 144 (94.7%) patients. Whereas for the effect on radiation dermatitis area, rhEGF showed improved effect on the radiation dermatitis area of 46 (30.2%) patients, detrimental effect on 15 (9.9%) patients, and no effect on 91 (59.9%) patients. The radiation dermatitis area of rhEGF side was significantly smaller than that of control side (P = 0.0007). CONCLUSIONS: rhEGF is a skin protective reagent for rectal and anal cancer patients receiving radiotherapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier: ChiCTR1900020842; Date of registration: 20/01/2019.

A Novel m7G-Related Gene Signature Predicts the Prognosis of Colon Cancer.

Colon cancer (CC), one of the most common malignancies worldwide, lacks an effective prognostic prediction biomarker. N7-methylguanosine (m7G) methylation is a common RNA modification type and has been proven to influence tumorigenesis. However, the correlation between m7G-related genes and CC remains unclear. The gene expression levels and clinical information of CC patients were downloaded from public databases. Twenty-nine m7G-related genes were obtained from the published literature. Via unsupervised clustering based on the expression levels of m7G-related genes, CC patients were divided into three m7G clusters. Based on differentially expressed genes (DEGs) from the above three groups, CC patients were further divided into three gene clusters. The m7G score, a prognostic model, was established using principal component analysis (PCA) based on 15 prognosis-associated m7G genes. KM curve analysis demonstrated that the overall survival rate was remarkably higher in the high-m7G score group, which was much more significant in advanced CC patients as confirmed by subgroup analysis. Correlation analysis indicated that the m7G score was associated with tumor mutational burden (TMB), PD-L1 expression, immune infiltration, and drug sensitivity. The expression level of prognosis-related m7G genes was further confirmed in human CC cell lines and samples. This study established an m7G gene-based prognostic model (m7G score), which demonstrated the important roles of m7G-related genes during CC initiation and progression. The m7G score could be a practical biomarker to predict immunotherapy response and prognosis in CC patients.