Effectiveness and safety of neoadjuvant apatinib in combination with capecitabine and oxaliplatin for the therapy of locally advanced colorectal cancer: A retrospective study.

The goal of the present study was to appraise the efficacy and safety of neoadjuvant apatinib in combination with capecitabine and oxaliplatin (XELOX) in patients with locally advanced colorectal cancer (CRC), as relevant data on its usage in this setting are lacking. A retrospective analysis was implemented on 100 patients with locally advanced CRC who received either neoadjuvant apatinib in combination with XELOX (N=50) or neoadjuvant XELOX alone (N=50). Radiological response and pathological complete response rates were evaluated. Furthermore, the researchers obtained data pertaining to disease-free survival (DFS), overall survival, as well as adverse events. The consequences of the present study indicated that the neoadjuvant apatinib in combination with XELOX treatment approach yielded higher rates of radiological objective response (86.0 vs. 68.0%, P=0.032) and major pathological response (46.0 vs. 22.0%, P=0.011) compared with XELOX alone. These findings were further confirmed through multivariate logistic regression analyses (P=0.037 and P=0.008, respectively). Interestingly, the neoadjuvant apatinib in combination with XELOX treatment approach significantly prolonged DFS when compared with XELOX alone (P=0.033). In summary, the administration of neoadjuvant apatinib in combination with XELOX demonstrates superiority over the use of XELOX alone in terms of achieving a more favorable pathological response and a longer duration of DFS in patients diagnosed with locally advanced CRC.

Identification of the six-hormone secretion-related gene signature as a prognostic biomarker for colon adenocarcinoma.

BACKGROUND: Colon adenocarcinoma (COAD) is a globally prevalent cancer, with hormone secretion playing a crucial role in its progression. Despite this, there is limited understanding of the impact of hormone secretion on COAD prognosis. This study aimed to establish a prognostic signature based on hormone secretion-related genes and to elucidate the potential functional mechanisms of these genes in COAD. METHODS: Using data from The Cancer Genome Atlas COAD cohort (TCGA-COAD), six hormone secretion-related genes were identified (CYP19A1, FOXD1, GRP, INHBB, SPP1, and UCN). These genes were used to develop a Hormone secretion score (HSS), which was then evaluated using the Kaplan-Meier curve and multivariable Cox analysis. The HSS model was further validated with external GEO cohorts (GSE41258, GSE39582, and GSE87211). Functional enrichment analyses were performed, and the CIBERSORT and TIDE algorithms were used to assess tumor infiltration. RESULTS: The study developed a prognostic signature, dividing patients into HSS-high and HSS-low groups. The HSS-high group showed a notably worse prognosis within the TCGA-COAD dataset and in three independent datasets: GSE41258, GSE39582, and GSE87211. Moreover, the HSS-high group predicted a shorter overall survival rate in patients maintaining microsatellite stability (MSS). The functional analysis associated HSS-high with the hypoxic, epithelial-mesenchymal transition (EMT), and TGF-ß signaling pathways and correlated with distant and lymph node metastases. The tumor immune microenvironment analysis revealed an elevated CIBERSORT score in the HSS-high group, suggesting an association with tumor metastasis. Further, the HSS-high group showed a higher TIDE score, indicating that patients with high HSS scores are less likely to benefit from Immune Checkpoint Inhibitor (ICI) therapy. CONCLUSIONS: This study demonstrated the prognostic significance of a HSS signature based on six hormone secretion-related genes in COAD. The findings suggest that this gene signature may serve as a reliable biomarker for predicting survival outcomes in COAD patients.

Rs11479 in Thymidine Phosphorylase Associated with Prognosis of Patients with Colorectal Cancer Who Received Capecitabine-Based Adjuvant Chemotherapy.

Objective: Thymidine Phosphorylase (TYMP) gene was of potential significance in the process of colorectal cancer (CRC) development and played an important role in capecitabine metabolism. This study was to identify the association between TYMP polymorphism and prognosis of postoperative patients with CRC who received capecitabine-based adjuvant chemotherapy. Methods: A total of 218 patients with CRC who were treated with surgical resection and capecitabine-based adjuvant chemotherapy were included in this study retrospectively. Peripheral blood and peripheral blood mononuclear cell (PBMC) specimen of the patients were collected for the genotyping of TYMP polymorphism and TYMP mRNA expression, respectively. Univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, Cox regression analysis was adopted in multivariate analysis. The mRNA expression of TYMP according to genotype status was analyzed using non-parameter test. Results: Prevalence of rs11479 in TYMP among the 218 patients exhibited that minor allele frequency of rs11479 was 0.20 (GG 141 cases, GA 68 cases and AA 9 cases), which was in accordance with Hardy-Weinberg equilibrium (P=0.825). Association analysis suggested that the median disease-free survival (DFS) of patients with GG genotype and GA/AA genotype was 3.1 and 6.1 years, respectively (P=0.004). Furthermore, the median overall survival of patients with GG genotype and GA/AA genotype was 5.0 and 7.0 years, respectively (P=0.033). Multivariate Cox regression analysis exhibited that rs11479 polymorphism was an independent factor for DFS (HR = 1.64, P=0.009). Additionally, of the 65 PBMC specimens, mRNA expression results indicated that patients with GA/AA genotypes conferred significantly higher mRNA expression of TYMP than that of patients with GG genotype (P<0.001). Conclusion: Polymorphism rs11479 in TYMP gene might predict the prognosis of patients with CRC who received capecitabine-based adjuvant chemotherapy through mediation of the mRNA expression of TYMP. The conclusion of this study should be validated in prospective clinical trials subsequently.

Impact of a haplotype (composed of the APC, KRAS, and TP53 genes) on colorectal adenocarcinoma differentiation and patient prognosis.

BACKGROUND: Many types of gene mutation are associated with the drug resistance of cancer cells. XELOX is a new and efficient surgical adjuvant chemotherapy for colorectal adenocarcinoma. However, drug-resistant related genetic mutations associated with this treatment remain unknown. METHODS: Next-generation sequencing (NGS) was performed on 36 colorectal cancer patients to identify mutations among patients with residual tumors following preoperative chemotherapy. Enrichment and prognosis of these mutations were evaluated in a TCGA cohort. The pathology of cases with poor prognosis-related mutations was also determined. RESULTS: A sequence of SNPs associated with the APC, KRAS, and TP53 genes in 13 of 19 subjects with residual tumors after preoperative chemotherapy was identified. Using survival analysis data from 317 cases in the TCGA database, a prognosis-related haplotype composed of SNPs from APC, KRAS, and TP53 was assembled. Colorectal cancer patients with these mutations had a lower 5-year tumor-specific survival rate than those without (p < 0.05). Most patients with these mutations were at a higher clinical stage (III-IV) of disease. Enrolled subjects with the identified haplotype tended to have poor cancer cell differentiation. CONCLUSIONS: The prognosis-related haplotype can be used as a marker of drug resistance and prognosis in colorectal cancer patients after preoperative chemotherapy.

Genomic profiling of a patient with quadruple synchronous colorectal cancer: a case report.

BACKGROUND: Synchronous colorectal cancer (SCRC) is featured by the presence of multiple primary tumor lesions in a single patient at initial diagnosis. It is less common with the prevalence of approximately 3.5% among colorectal cancer (CRC). Some studies of SCRC have been performed in patients with two tumor lesions. However, SCRC cases with three or more tumor lesions were rare and remained to be investigated. CASE PRESENTATION: In this case report, we presented a 56-year-old male SCRC case with quadruple tumor lesions which is rarely seen in clinical practice. After laparoscopic radical resection of sigmoid carcinoma and partial rectum resection, the four tumor samples were subjected to pathological evaluation and next-generation sequencing (NGS) based genetic profiling. The four tumor lesions included two adenocarcinomas with moderate differentiation at sigmoid colon and rectum respectively, a grade 1 neuroendocrine tumor (NET) at rectum and a high-grade intraepithelial neoplasia at ascending colon. Each tumor exhibited distinct histology types and mutation profiles. After surgical resection, the patient remained disease-free after four cycles of chemotherapy with oxaliplatin and capecitabine (XELOX). CONCLUSIONS: The tumor lesions in this case showed different pathological and genetic features which indicats the heterogeneity of SCRC. The genomic profilling might provide novel insights to understand SCRC at molecular level.

Multiple differential expression networks identify key genes in rectal cancer.

BACKGROUND: Rectal cancer is an important contributor to cancer mortality. OBJECTIVE: The objective of this paper is to identify key genes across three phenotypes (fungating, polypoid and polypoid & small-ulcer) of rectal cancer based on multiple differential expression networks (DENs). METHODS: Differential interactions and non-differential interactions were evaluated according to Spearman correlation coefficient (SCC) algorithm, and were selected to construct DENs. Topological analysis was performed for exploring hub genes in largest components of DENs. Key genes were denoted as intersections between nodes of DENs and rectal cancer associated genes from Genecards. Finally, we utilized hub genes to classify phenotypes of rectal cancer on the basis of support vector machines (SVM) methodology. RESULTS: We obtained 19 hub genes and total 12 common key genes of three largest components of DENs, and EGFR was the common element. The SVM results revealed that hub genes could classify phenotypes, and validated feasibility of DEN methods. CONCLUSIONS: We have successfully identified significant genes (such as EGFR and UBC) across fungating, polypoid and polypoid & small-ulcer phenotype of rectal cancer. They might be potential biomarkers for classification, detection and therapy of this cancer.