Soohyeon Lee

Background: The treatment paradigm for locally advanced rectal cancer (LARC) is evolving toward total neoadjuvant therapy (TNT), emphasizing strategies to maximize tumor regression and enable organ preservation. Identifying host-related biomarkers that predict response to neoadjuvant chemoradiotherapy (CRT) has therefore become increasingly important. Although body composition has been associated with cancer prognosis, the distinct roles of skeletal muscle and adipose tissue dynamics in treatment tolerance and tumor response remain unclear. This study aimed to develop a multivariable prediction model for tumor response and treatment tolerance based on body composition dynamics during CRT. Methods: In this single-center retrospective cohort study conducted at a tertiary referral hospital, 138 patients with LARC who underwent neoadjuvant CRT were analyzed. Baseline and post-CRT body composition parameters (skeletal muscle and adipose indices at the L3 level) and clinicolaboratory variables were evaluated as predictors. The primary outcome was high TRG (tumor regression grade 3–4), and the secondary outcome was CRT-related adverse events (CRT-AEs). A multivariable logistic regression model was developed, with continuous variables standardized. Model performance was assessed using the area under the receiver operating characteristic curve (AUC) and decision curve analysis. Internal validation was performed using 1,000 bootstrap resamples. Results: High TRG was observed in 33.3% of patients. Multivariable analysis demonstrated that the absence of CRT-AEs, higher baseline subcutaneous fat index, and a smaller reduction in visceral fat during CRT were independently associated with high TRG (all PConclusions: Body composition appears to play compartment-specific roles during neoadjuvant CRT in rectal cancer. Skeletal muscle status primarily reflects treatment tolerance, whereas adipose tissue dynamics are more closely associated with tumor regression. These computed tomography (CT)-based metrics may serve as practical, noninvasive indicators to support risk stratification and personalized treatment strategies in the era of TNT.

Radiotherapy is a cornerstone of colorectal cancer (CRC) treatment; however, its therapeutic efficacy is often compromised by both intrinsic and acquired resistance in CRC cells. This study employed small interfering RNA (siRNA) technology to elucidate the functional roles of BAMBI, GADD34, NFKBIA, and NFKBID in CRC cell lines SW480 and HCT116. We assessed their impact on key cellular processes and radiation sensitivity. Gene silencing of all four target genes significantly suppressed CRC cell proliferation, migration, and invasion. Moreover, siRNA-mediated knockdown enhanced radiation sensitivity, as evidenced by a substantial increase in apoptosis and a marked reduction in cell viability compared with controls. These findings suggest that BAMBI, GADD34, NFKBIA, and NFKBID serve as critical regulators of CRC progression and radiation resistance. Overall, this study provides a mechanistic foundation for further exploration into the pathways underlying radiation resistance and underscores the potential for developing personalized radiotherapy strategies guided by molecular profiling.

Colorectal cancer (CRC) is one of the most common and deadly cancers in the world. However, no effective treatment for the disease has yet been found. For this reason, several studies are being carried out on the treatment of CRC. Currently, there is limited understanding of the role of CPNE7 (copine-7) in CRC progression and metastasis. The results of this study show that CPNE7 exerts an oncogenic effect in CRC. First, CPNE7 was shown to be significantly up-regulated in CRC patient tissues and CRC cell lines compared to normal tissues according to IHC staining, qRT-PCR, and western blotting. Next, this study used both systems of siRNA and shRNA to suppress CPNE7 gene expression to check the CPNE7 mechanism in CRC. The suppressed CPNE7 significantly inhibited the growth of CRC cells in in vitro experiments, including migration, invasion, and semisolid agar colony-forming assay. Moreover, the modified expression of CPNE7 led to a decrease in the levels of genes associated with epithelial–mesenchymal transition (EMT). The epithelial genes E-cadherin (CDH1) and Collagen A1 were upregulated, and the levels of mesenchymal genes such as N-cadherin (CDH2), ZEB1, ZEB2, and SNAIL (SNAL1) were downregulated after CPNE7 inhibition. This study suggests that CPNE7 may serve as a potential diagnostic biomarker for CRC patients.

Purpose: Cancer patients receiving various anti-cancer treatments commonly experience malnutrition, and many studies have reported that nutritional status is associated with survival and prognosis. Although standard neoadjuvant chemoradiotherapy (CRT) is commonly used in patients with locally advanced rectal cancer owing to its tumor-downsizing and downstaging effects, there is a lack of research on the impact of patients’ nutritional status on the efficacy of neoadjuvant CRT.Methods: We investigated the immunonutritional markers before and after long-course neoadjuvant CRT in 131 patients diagnosed with locally advanced rectal cancer from March 2013 to March 2022.Results: We divided the patients into two groups: a low prognostic nutritional index (PNI) with a cutoff value of 50.92, and a high PNI. In both groups, significant decreases in lymphocyte count and PNI and an increase in neutrophil-to-lymphocyte ratio (NLR) were observed before and after CRT (P<0.001). Furthermore, a higher proportion of patients experienced adverse effects in the low PNI group than in the high PNI group (76.6% in low PNI vs. 54.8% in high PNI, P=0.013). The most commonly reported CRT-induced adverse effect was lower gastrointestinal tract toxicity.Conclusion: By measuring the PNI and NLR without additional tests prior to starting neoadjuvant CRT in patients with locally advanced rectal cancer, it is possible to predict the risk of acute adverse effects caused by CRT. Additionally, providing external nutritional support to reduce the immunonutritional changes that occur during CRT can decrease side effects and potentially increase treatment compliance.

Patients with colorectal cancer (CRC) often fail to complete full-course chemotherapy with a standard dose due to various reasons. This study aimed to determine whether body composition affects chemotherapy adherence in patients with CRC. The medical records of 107 patients with stage III CRC who underwent adjuvant folinic acid, fluorouracil and oxaliplatin (FOLFOX) chemotherapy at a single center between 2014 and 2018 were analyzed retrospectively. Blood test results for selected immunonutritional markers were analyzed and body composition was measured through computed tomography. Univariate and multivariate analyses were performed on low and high relative dose intensity (RDI) groups, based on an RDI of 0.85. In the univariate analysis, a higher skeletal muscle index was correlated with a higher RDI (p = 0.020). Psoas muscle index was also higher in patients with high RDI than in those with low RDI (p = 0.026). Fat indices were independent of RDI. Multivariate analysis was performed for the aforementioned factors and results showed that age (p = 0.028), white blood cell count (p = 0.024), and skeletal muscle index (p = 0.025) affected RDI. In patients with stage III CRC treated with adjuvant FOLFOX chemotherapy, a decrease in RDI was related to age, white blood cell count, and skeletal muscle index. Therefore, if we adjust the drug dosage in consideration of these factors, we can expect an increased treatment efficiency in patients by increasing chemotherapy compliance.