ALDOC regulated the biological function and immune infiltration of gastric cancer cells.

BACKGROUND: The role of ALDOC which is an important regulator involved in tumor metabolic reprogramming and immune microenvironment in GC remains unclear. Therefore, we investigated the feasibility of ALDOC as a prognostic marker and therapeutic target. METHODS: We verified the expression of ALDOC in GC and its effect on the prognosis of GC patients by analyzing clinical data. The regulation of ALDOC on the biological behavior of GC cells was confirmed by experiments. The potential mechanism of miRNA regulating GC immune cell infiltration by inhibiting ALDOC was explored by experiments and bioinformatic analysis. We further analyzed the effect of ALDOC on somatic mutations in gastric cancer, and constructed a prognostic model based on ALDOC and related immune molecules. RESULTS: ALDOC is overexpressed in GC cells and tissues, which promotes malignant biological behavior of GC cells and is an independent risk factor for poor prognosis of GC patients. MiR-19a-5p promotes the expression of ALDOC by down-regulating ETS1, leading to poor prognosis in GC patients. ALDOC is significantly associated with immune infiltration in GC, regulates macrophage differentiation and promotes the progression of GC. ALDOC is significantly correlated with TMB and MSI of gastric cancer, and affects somatic mutation of gastric cancer. The prognostic model has good predictive efficiency. CONCLUSIONS: ALDOC is a potential prognostic marker and therapeutic target with abnormal immune-mediated effects. The prognostic model based on ALDOC provides a reference for prognosis prediction and individualized treatment of GC patients.

[Association of genomic instability of CDH1 gene with clinicopathological characteristics of gastric cancer].

OBJECTIVE: To assess the association of genomic instability of epithelial cadherin 1 (CDH1) gene and clinicopathological characteristics of gastric cancer. METHODS: In total 120 paraffin-embedded gastric cancer tissue specimen were prepared, and genomic DNA was extracted. The genomic instability of the CDH1 gene was analyzed by immunohistochemistry and silver staining PCR-single-strand conformation polymorphism. RESULTS: The number of information individuals (heterozygotes) was 98 for the D16S752 locus. The detection rates for microsatellite instability (MSI) and loss of heterozygosity (LOH) at the D16S752 locus and the positive rate of CDH1 protein were 19.39%, 16.33% and 51.02%, respectively. The detection rate of MSI in TNM stages I or II was significantly higher than that in stages III or IV (P<0.05) while the detection rate of LOH was significantly lower than that in stages III or IV (P<0.05). The positive rate of CDH1 protein in TNM stages III or IV was significantly lower than that in stages I or II (P<0.05). The detection rate of MSI of cases with lymph node metastasis was significantly lower than that of without lymph node metastasis (P<0.05) while the detection rate of LOH was significantly higher than that without lymph node metastasis (P<0.05). The positive rate of CDH1 protein in patients with lymph node metastasis was significantly lower than that in patients without lymph node metastasis (P<0.05). The positive rate of CDH1 protein in MSI-positive group was significantly higher than that in MSI-negative group (P<0.05), and the positive rate of CDH1 protein in the LOH-positive group was significantly lower than that the LOH-negative group (P<0.05). CONCLUSION: The genomic instability of the CDH1 gene is associated with the progression of gastric cancer. MSI at the D16S752 locus may be used as a molecular marker for early gastric cancer, while LOH at this locus mostly occurs in advanced gastric cancer and can be regarded as an effective indicators for malignancy evaluation and prognosis.

[Relationship of preoperative and postoperative myeloid-derived suppressor cells percentage with the prognosis in rectal cancer patients].

OBJECTIVE: To observe the change of myeloid-derived suppressor cells (MDSCs) percentage in peripheral blood after operation in rectal cancer patients and to examine its association with the prognosis. METHODS: Blood samples of pre-operation and postoperative 21-day from 64 stage I(-III( rectal cancer patients who underwent surgery in Department of General Surgery, The Affiliated Cancer Hospital, Zhengzhou University between January and December 2009 were collected. MDSCs percentage was detected by flow cytometry. Its association with the prognosis of patients was analyzed. RESULTS: MDSCs percentage of postoperative 21-day decreased significantly compared with pre-operation (P<0.01). When local recurrence or distant metastasis presented, MDSCs percentage increased again (all P<0.01) and reached the preoperative level(P>0.05). All the patients were further divided into two groups based on median MDSCs percentage. Patients with higher MDSCs percentage before operation (>3.78%) and after operation (>2.11%) had significantly lower 5-year overall survival(OS) (58.1% and 62.1%) and 5-year disease-free survival (DFS)(54.8% and 58.6%) as compared to those with lower MDSCs percentage(5-year OS 87.9% and 84.8%; 5-year DFS 82.8% and 80.0%, all P<0.05). Multivariate analysis showed that preoperative MDSCs percentage was an independent prognostic factor of rectal cancer(HR:4.065, 95% CI:1.026 to 16.108, P=0.04). CONCLUSIONS: Preoperative increased MDSCs percentage may be an important predictor of poor OS in rectal cancer patients. Dynamic change of MDSCs percentage can reflect the disease development.

Expression of P-aPKC-iota, E-cadherin, and beta-catenin related to invasion and metastasis in hepatocellular carcinoma.

OBJECTIVES: Atypical protein kinase C iota (aPKC-iota) and its associated intracellular molecules, E-cadherin and beta-catenin, are important for cell polarization in tumorigenesis and progression. Expression of aPKC-iota, P-aPKC-iota (activated aPKC-iota), E-cadherin, and beta-catenin in hepatocellular carcinoma (HCC) was measured, and correlation with clinicopathological characteristics of HCC was analyzed. METHODS: Paraffin-embedded tumor tissue was obtained from patients with HCC after resection without preoperative radiotherapy or chemotherapy. Gene expression was detected by polymerase chain reaction (PCR), and protein expression was detected by immunohistochemistry and Western blot analysis. Expressions of aPKC-iota, P-aPKC-iota, E-cadherin, and beta-catenin were analyzed with relation to the clinicopathological data. RESULTS: The gene and protein expression of aPKC-iota are obviously higher in HCC tissues than that in peritumoral tissues and normal tissues by semiquantitative PCR and immunohistochemistry methods. Accumulation of aPKC-iota in HCC cytoplasm and nucleolus inhibited the later formation of belt-like adherens junctions (AJs) and/or tight junctions (TJs) in cell-cell contact. E-cadherin was reduced and accumulation of cytoplasm beta-catenin was increased in HCC. The expression of aPKC-iota was closely related to pathological differentiation, tumor size, invasion, and metastasis of HCC. CONCLUSION: Accumulation of cytoplasm aPKC-iota may reflect pathological differentiation, invasion, and metastasis potential of HCC. In this regard, our study on HCC revealed the potential usefulness of aPKC-iota, E-cadherin, and beta-catenin as a prognostic marker, closely related to pathological differentiation, invasion, metastasis, and prognosis of HCC.