Perovskite Probe-Based Machine Learning Imaging Model for Rapid Pathologic Diagnosis of Cancers.

Accurately distinguishing tumor cells from normal cells is a key issue in tumor diagnosis, evaluation, and treatment. Fluorescence-based immunohistochemistry as the standard method faces the inherent challenges of the heterogeneity of tumor cells and the lack of big data analysis of probing images. Here, we have demonstrated a machine learning-driven imaging method for rapid pathological diagnosis of five types of cancers (breast, colon, liver, lung, and stomach) using a perovskite nanocrystal probe. After conducting the bioanalysis of survivin expression in five different cancers, high-efficiency perovskite nanocrystal probes modified with the survivin antibody can recognize the cancer tissue section at the single cell level. The tumor to normal (T/N) ratio is 10.3-fold higher than that of a conventional fluorescent probe, which can successfully differentiate between tumors and adjacent normal tissues within 10 min. The features of the fluorescence intensity and pathological texture morphology have been extracted and analyzed from 1000 fluorescence images by machine learning. The final integrated decision model makes the area under the receiver operating characteristic curve (area under the curve) value of machine learning classification of breast, colon, liver, lung, and stomach above 90% while predicting the tumor organ of 92% of positive patients. This method demonstrates a high T/N ratio probe in the precise diagnosis of multiple cancers, which will be good for improving the accuracy of surgical resection and reducing cancer mortality.

Comprehensive characterization of PKHD1 mutation in human colon cancer.

INTRODUCTION: The PKHD1 (Polycystic Kidney and Hepatic Disease 1) gene is essential for producing fibrocystin or polyductin, which is crucial in various cellular functions. Mutations in PKHD1 have been found to be involved in the development and progression of colorectal cancer (CRC). Along with APC, TP53, and KRAS, PKHD1 is one of the most frequently mutated genes in CRC. PKHD1 expression is governed by the Wnt/PCP pathway, often dysregulated in CRC. Targeting this pathway, crucial for CRC progression, could unveil potential therapeutic strategies for colon cancer treatment. METHODS: This study examined an in-house dataset of 3702 colon cancer samples, analyzing mutation landscapes, clinical features, tumor mutational burden (TMB), microsatellite instability (MSI), and chromosomal instability (CIN) score. For the survival analysis of PKHD1 patients, survival data of 436 colon adenocarcinoma samples were obtained from TCGA dataset. Additionally, 433 samples from TCGA with RNA-seq data were used for the assessment of immune cell infiltration and gene set enrichment analysis. RESULTS: Polycystic Kidney and Hepatic Disease 1 mutation was detected in 424 colon cancer patients from our in-house cohort and was associated with increased TMB, higher MSI, and lower CIN score. Importantly, within the TCGA dataset, PKHD1 mutations were identified as an independent prognostic factor, not merely correlated with established prognostic biomarkers, and were associated with poorer overall survival outcomes. In terms of immune response, these mutations correlated with increased enrichment scores for 12 immune cell types, including B cell plasma, macrophages, and naive CD4+ T cells. Additionally, interferon alpha and interferon-gamma gene sets were significantly down-regulated in patients with PKHD1 mutations (FDA q-value < 0.1). CONCLUSIONS: Overall, these findings suggest that PKHD1 may be a potential biomarker for the prognosis of colon cancer and provide some insight for personalized immunotherapy.

Evaluation of the advantages of robotic versus laparoscopic surgery in elderly patients with colorectal cancer.

BACKGROUND: The incidence of colorectal cancer increases with aging. Curative-intent surgery based on a minimally invasive concept is expected to bring survival benefits to elderly patients (aged over 80 years) with colorectal cancer who are frequently with fragile health status and advanced tumors. The study explored survival outcomes in this patient population who received robotic or laparoscopic surgery and aimed to identify an optimal surgical option for those patients. METHODS: We retrieved the clinical materials and follow-up data on elderly patients with colorectal carcinoma who received robotic or laparoscopic surgery in our institution. The pathological and surgical outcomes were compared to examine the efficacy and safety of the two approaches. The DFS (disease-free survival) and OS (overall survival) results at 3 years after surgery were assessed to explore the survival benefits. RESULTS: A total of 111 patients were screened for the study, including 55 in the robotic group and 56 in the laparoscopic group. The demographic details were generally similar between the two groups. No statistically significant difference in the number of removed lymph nodes was observed between the two approaches, with a median of 15 versus 14 (P = 0.053). The intraoperative blood loss was significantly reduced by robotic technique when compared to the laparoscopic approach, with a mean of 76.9 ml versus 161.6 ml (P = 0.025). There were no significant differences in operation time, conversion, postoperative complications and recovery, and long-term outcomes between the two groups. CONCLUSION: Robotic surgery was prized for elderly patients with colorectal cancer who developed anemia and/or hematological conditions.

The postoperative clinical outcomes and safety of early enteral nutrition in operated gastric cancer patients.

PURPOSE: This study investigated the impact of early enteral nutrition (EEN) on the clinical outcomes of gastric cancer patients after radical gastrectomy. METHODS: Four hundred gastric cancer patients undergoing radical gastrectomy of any extend with D2 nodal dissection were randomly divided into an experimental and a control group with 200 cases in each group. Patients in the control group received postoperative parenteral nutrition (PN), while patients in the experimental group received postoperative EEN. After treatment, the clinical outcomes, postoperative immune function, and nutritional status of the two groups were evaluated. RESULTS: The postoperative fever time, intestinal function recovery time, anal exhaust time, and the length of hospital stay for patients in the experimental group were significantly shorter than those of the control group. We did not find significant differences in anastomotic leak, postoperative ileus and regurgitation between the two groups. The activities of multiple immune cell types, including CD3⁺, CD4⁺, CD4⁺/CD8⁺, and natural killer (NK) cells, were significantly lower in both groups on postoperative day 1 when compared with the preoperative levels (p<0.05). The level of CD8⁺ was not significantly different between the two groups (p>0.05). After treatment, levels of CD3⁺, CD4⁺, CD4⁺/CD8⁺, and NK cells in the experimental group patients were 35.6 ± 4.2, 42.2 ± 3.0, 1.7 ± 0.3, and 27.3 ± 5.3%, respectively, on postoperative day 7, which were similar to the preoperative levels. The immune cell levels from the control group patients remained significantly lower when compared with preoperative values; in addition, these values were also significantly lower when compared with the EEN patients (p<0.05) CONCLUSION: For gastric cancer patients undergoing radical gastrectomy, the clinical outcome, immune function and nutritional status after EEN were significantly improved. These data suggest the widespread use of EEN in clinical practice.

Microsatellite instability of gastric cancer and precancerous lesions.

OBJECTIVE: To investigate whether microsatellite instability (MSI) of gastric cancer and precancerous lesions were existed and its effect. METHODS: Laser microdissection was used. Gastric, intestinal metaplasia, dysplasia and normal mucosa were collected respectively. Five microsatellite loci were selected and MSI was detected by denaturing high-performance liquid chromatography. RESULTS: In the five microsatellite loci REF-positive phenotype, intestinal metaplasia MSI was 20.7%. Dysplasia MSI was 22.4%. Gastric MSI was 47.9%, and there was no MSI in normal gastric mucosa. CONCLUSION: MSI gradually increased from precancerous lesions to gastric cancer. The early detection of MSI may be a potential early warning indicator for early diagnosis of gastric cancer.

Detection of microsatellite instability in gastric cancer and dysplasia tissues.

OBJECTIVE: We aimed to investigate the association between gastric cancer and microsatellite instability (MSI) in the present study. METHOD: Phenol-chloroform method was employed for DNA extraction from the cancer tissues of 65gastric cancer patients and the dysplasia tissues and normal control tissues of 32 non-gastric cancer patients. The microsatellite loci Bat25, Bat26, D2S123, D5S346 and D17S250 were detected by using PCR-SSCP silver staining technique, and the MSI of the gastric cancer tissues and the precancerous tissues was analyzed. RESULTS: Of 65 gastric cancer cases, MSI was detected in 43 cases, with the detection rate of 66.2%. There were 13 cases showing MSI-H and 30 cases showing MSI-L, accounting for 30.2% and 69.8%, respectively. Among 32 cases of dysplasia tissues, MSI was detected in 10 cases, with the detection rate of 31.3%. Two cases of dysplasia tissues showed MSI-H and 8 cases showed MSI-L, accounting for 20.0% and 80.0%, respectively. CONCLUSION: Gastric cancer patients had a high detection rate of MSI. It is speculated that MSI is another molecular mechanism of carcinogenesis and may serve as a sensitive diagnostic indicator of gastric cancer.

Molecular epidemiologic correlation analysis between caspase3 gene polymorphism and gastric cancer susceptibility.

The objective was to analyze the relation between gastric cancer susceptibility and gene polymorphism, providing a reference for epidemiologic research of gastric cancer etiology. Two hundred and eighty gastric cancer cases were selected, and 280 healthy cases with the same gender, age (± 5), and residence place were selected as control group, with proportion of 1:1. Tag single nucleotide polymorphism was used for screening polymorphism of caspase3, which was combined with logistic regression model and multi-point joint analysis to analyze relation between different genotypes and gastric susceptibility. In analysis of gene polymorphism of caspase3 intrinsic apoptotic pathway and gastric cancer susceptibility, polymorphism of CASP3 rs4647693, CASP3 rs12108497 and CASP3 rs4647610 increased gastric cancer risk (rs4647693: ORGA 1.61, 95 % CI 1.06-2.28; rs12108497: ORTC 1.55, 95 % CI 1.09-2.18; ORCC 2.45, 95 % CI 1.08-4.16; rs4647610: ORAG 1.71, 95 % CI 1.14-2.31; ORGG 1.60, 95 % CI 1.23-2.34). Gastric cancer risk of haplotype AGGC carrier was significantly higher than that of haplotype GGAT as control (OR 1.44, 95 % CI 1.07-2.19). Gene polymorphism and haplotype of caspase3 can increase gastric cancer risk. However, it still needs to be verified by a large-sample and multicenter epidemiologic research.

A missense mutation (S3660L) in MLL3 gene influences risk of gastric cancer.

PURPOSE: Several studies indicated that the expression level of MLL3 gene in gastric cancer tissue was associated with prognosis, and previous studies also suggested that genetic polymorphisms of MLL3 were related to the risk for gastric cancer. The present study aimed to investigate the association of a missense mutation (S3660L) in the MLL3 gene with gastric cancer risk in a Chinese population. METHODS: In the present study, we identified a novel missense mutation in MLL3 gene (S3660L) by directly sequencing method in 48 gastric cancer patients. To further explore the relation between gastric cancer and this mutation, we selected 354 gastric cancer patients and 377 healthy control subjects and designed a case-control study. RESULTS: We found that the AG genotype (14.9 vs 6.40%, odds ratio/OR=2.58, 95% CI: 1.33-4.54, p<0.001) and A allele (7.5 vs 3.2%, OR=2.46, 95% CI: 1.55~5.34, p<0.001) were common in the gastric cancer patients than in the control subjects. CONCLUSION: We concluded that this novel missense (S3660L) mutation in MLL3 gene is likely to increase the gastric cancer risk.

Mll3 genetic variants affect risk of gastric cancer in the chinese han population.

It is reported that the expression level of MLL3 in gastric cancer tissue highly correlates with tumor progression. However, whether MLL3 genetic variants are associated with the risk of gastric cancer remains unclear. In this study, we conducted a genotyping analysis for MLL3 in 314 cases of gastric cancer and 322 controls from the Chinese Han population. 4 SNPs (rs6943984, rs4725443, rs3800836, rs6464211) were selected for the present analysis. We found 2 SNPs (rs6943984, rs4725443) of MLL3 gene were significantly associated with the risk of gastric cancer : the rs6943984 with the minor allele A and rs4725443 with the minor allele C revealed strong associations with increased gastric cancer risk [P <0.001, OR=1.97, 95% CI=1.48~2.64 and P <0.001, OR = 2.23, 95% CI = 1.54~3.24]. Haplotype analysis of the four SNPs showed that haplotype A-T-A-C, G-T-G-C, and G-C-A-C increased the risk of gastric cancer (P <0.001, P=0.18, and P<0.001, respectively), while haplotype G-T-A-C significantly reduced the risk of gastric cancer (P <0.001). We concluded that MLL3 variants are significantly associated with gastric cancer risk. Our results for the first time provided new insight into susceptibility factors of MLL3 gene variants in carcinogenesis of gastric cancer of the Chinese Han population.