ObjectiveTo investigate the relation between disulfidptosis-related genes (DRGs) and prognosis or immunotherapy response of patients with pancreatic cancer (PC). MethodsThe transcriptome data, somatic mutation data, and corresponding clinical information of the patients with PC in The Cancer Genome Atlas (TCGA) were downloaded. The DRGs mutated in the PC were screened out from the 15 known DRGs. The DRGs subtypes were identified by consensus clustering algorithm, and then the relation between the identified DRGs subtypes and the prognosis of patients with PC, immune cell infiltration or functional enrichment pathway was analyzed. Further, a risk score was calculated according to the DRGs gene expression level, and the patients were categorized into high-risk and low-risk groups based on the mean value of the risk score. The risk score and overall survival of the patients with high-risk and low-risk were compared. Finally, the relation between the risk score and (or) tumor mutation burden (TMB) and the prognosis of patients with PC was assessed. ResultsThe transcriptome data and corresponding clinical information of the 177 patients with PC were downloaded from TCGA, including 161 patients with somatic mutation data. A total of 10 mutated DRGs were screened out. Two DRGs subtypes were identified, namely subtype A and subtype B. The overall survival of PC patients with subtype A was better than that of patients with subtype B (χ2=8.316, P=0.003). The abundance of immune cell infiltration in the PC patients with subtype A was higher and mainly enriched in the metabolic and conduction related pathways as compaired with the patients with subtype B. The mean risk score of 177 patients with PC was 1.921, including 157 cases in the high-risk group and 20 cases in the low-risk group. The risk score of patients with subtype B was higher than that of patients with subtype A (t=14.031, P<0.001). The overall survival of the low-risk group was better than that of the high-risk group (χ2=17.058, P<0.001), and the TMB value of the PC patients with high-risk was higher than that of the PC patients with low-risk (t=5.642, P=0.014). The mean TMB of 161 patients with somatic mutation data was 2.767, including 128 cases in the high-TMB group and 33 cases in the low-TMB group. The overall survival of patients in the high-TMB group was worse than that of patients in the low-TMB group (χ2=7.425, P=0.006). ConclusionDRGs are closely related to the prognosis and immunotherapy response of patients with PC, and targeted treatment of DRGs might potentially provide a new idea for the diagnosis and treatment of PC.
ObjectiveTo summarize the research progress of KRAS mutation in pancreatic tumorigenesis and therapy.MethodThe research progress of KRAS mutation in pancreatic tumorigenesis and therapy were summarized by reading the domestic and international literatures published in recent years.ResultsPancreatic cancer had the title of " king of cancer”. More than 90% of pancreatic cancer patients had KRAS mutation. KRAS had a complex relationship with pancreatic cancer through downstream signaling pathways, including Raf (rapidly accelerated fibrosarcoma)-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK), phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K)-protein kinase B (AKT), and RalGDS-Ral. Although basic research on pancreatic cancer was deepening, there was still a lack of effective molecular targeted drugs.ConclusionsKRASgene plays an important role in the occurrence of pancreatic cancer. The treatment associated with KRAS mutation provides a more effective prognostic possibility for pancreatic cancer patients.
ObjectiveTo observe and analyze the clinical phenotype and genetic characteristics of COL2A1 and COL11A1 de novo mutation (DNM) related Stickler syndrome type Ⅰ and Ⅱ patients. MethodsA family-based cohort study. From December 2023 to November 2024, 4 patients (all probands) with Stickler syndrome diagnosed by clinical and genetic testing in Department of Ophthalmology of People's Hospital of Ningxia Hui Autonomous Region and their parents (8 cases) were included in the study. The patients came from 4 unrelated families. A detailed medical history was taken, and the patients underwent best-corrected visual acuity (BCVA), refraction, and fundus color photography examinations. Systemic examinations included the oral and facial regions, skeletal, joints, and hearing. Peripheral venous blood samples were collected from the patients and their parents, and genomic DNA was extracted. Whole-exome sequencing was used to screen for pathogenic genes and their loci, which were then validated by Sanger sequencing and combined with segregation analysis in the families to identify candidate gene mutation sites. The candidate variants were assessed for pathogenicity according to the American College of Medical Genetics and Genomics (ACMG) criteria and guidelines for the classification of genetic variants. Additionally, cross-species conservation analysis was performed to determine the evolutionary conservation of wild-type amino acids, and protein three-dimensional modeling techniques were used to characterize the spatial conformational changes of the variant proteins and the alterations in their local hydrogen bond networks. ResultsAmong the 4 patients, there were 2 males and 2 females; their ages ranged from 3 to 12 years. There were 2 cases of Stickler syndrome type Ⅰ (proband of families 1 and 2) and 2 cases of type Ⅱ (proband of families 3 and 4). The diopters ranged from −8.00 to−18.00 D. BCVA ranged from no light perception to 0.6-. There were 2 cases each of vitreous membrane-like and “bead-like” opacity. Three cases showed peripapillary atrophy arcs and leopard pattern changes in the retina; one case had bilateral retinal detachment with a large macular hole in the left eye, which had previously been treated with vitrectomy surgery. One case had bilateral sensorineural hearing loss. There were 3 cases of simple micrognathia; one case had a flat nasal bridge, short nose, midface depression, and micrognathia. Two cases had excessive elbow joint extension. The phenotypes of the parents of the 4 patients were normal. Genetic testing results revealed that the probands of families 1 and 2 carried COL2A1 gene c.85+1G>C (M1) splice site variant and c.3950_3951insA (p.M1317Ifs*48) (M2) frameshift variant, respectively; the probands of families 3 and 4 carried COL11A1 gene (NM_001854.4) c.2549 G>T (p.G850V) (M3) missense variant and c.3816+6T>C (M4) splice site variant, respectively. The parents did not carry the related gene variants. Among them, M2, M3, and M4 are newly reported DNM. According to the ACMG guidelines, they were all considered likely pathogenic. The cross-species conservation analysis results showed that the wild-type amino acid of the COL11A1 gene M3 missense variant was highly conserved across multiple different species. Protein local structure modeling analysis revealed that the COL2A1 gene M2 frameshift variant and the COL11A1 gene M3 missense variant significantly altered the tertiary structure conformation of the protein, leading to abnormal spatial arrangement and hydrogen bond network in the key functional domains ConclusionThe COL2A1 gene M1 splice site variant, M2 frameshift variant, and the COL11A1 gene M3 missense variant, M4 splice site variant are respectively the potential pathogenic genes for families 1, 2, and families 3, 4; leading to the onset of Stickler syndrome type Ⅰ in families 1 and 2, and type Ⅱ in families 3 and 4.
Purpose To investigate the relationship between mitochondrial DNA 11778 mutation and clinical characteristics of patients with Laber is hereditary optic neuropathy(LHON). Methods PCR RFLPs (MaeⅢ) and mutation specific primer PCR(MSP-PCR) were used simultaneously to detect mitochondrial DNA 11778 mutation. Results Among 10 subjects who habored 11778 mutation,one was a carrier and nine were patients with LHON.Of the nine patients,six were males and three were females.The age of onset ranged from 12 to 25 years old and the onset interval of the two eyed varied between 0 to 6 months. The visual acuity was CF/10cm-0.1 except one who lost her vision after delivery but recovered gradually.The results of visual field,VEP and color vision were abnormal but ERG and systemic status were all normal. Conclusion Molecular biological detection of the ten subjects showed that they all habored mtDNA 11778 mutation.The existence of carrier and visual recovery imlied that mtDNA mutation was a primary cause of LHON,but other factors such as endocrine disorder might influence the pathogenesis of LHON. (Chin J Ocul Fundus Dis,1998,14:156-158)
ObjectiveTo summarize the progress in mutant gene sequences of different types of hereditary colorectal cancer.MethodThe relevant literatures about genetic mutations in hereditary colorectal cancer at home and abroad were reviewed.ResultsHereditary colorectal cancer coule be divided into two categories according to whether it was related to the germline mutations of known oncogenes. Among the known germline mutant genes, the gene of adenomatous polyposis coli (APC), MUTYH, thymidine glycol DNA glycosylase 1 (NTHL1), polymerase (DNA) epsilon, catalytic subunit (POLE), and polymerase (DNA) delta 1, catalytic subunit (POLD1) were closely related to adenomatous polyposis syndromes, mismatch repair (MMR)-related genes were related to Lynch syndrome, serine/threonine kinase 11 (STK-11) gene was related to Peutz-Jeghers syndrome, mutant genes of SMAD4 and bone morphogenetic protein receptor type 1A (BMPR1A) were found in JPS individuals, and Cowden syndrome was caused by phosphatase and tensin homology deleted on chromosome ten (PTEN) gene mutation. For colorectal cancer patients with unknown germline mutations but significant genetic characteristics (such as hyperplastic polyposis), relevant genes had also been gradually searched out, which needed further evidence.ConclusionsColorectal cancer is a malignant tumor with genetic characteristics. Compared with sporadic colorectal cancer, the time of hereditary colorectal cancer from adenoma to cancer is shorter, and the occurrence of heterogeneous tumor is also increased, but the survival rate after active intervention is higher than the sporadic one. To study the mutant gene sequences of hereditary colorectal cancer is the improvement and development of the diseases control in modern medicine.
Objective To study the mutations at 1 573 fragment of TNF receptor II (TNFR-II) gene in patients with keloid. Methods The tissue DNA was extracted from 22 samples of keloids donated by 22 patients (6 males and 16 females, aged 18-53 years), and all keloids were examined and classified by pathologist. The peri pheral blood DNA was extracted from the same patients as the control. PCR was used to ampl ify the 1 573 fragment of TNFR-II gene from the keloid tissue DNA and peripheral blood DNA. The PCR products were sequenced directly and then compared with the GeneBankdata. Results All the concentration of the extracted DNA in trial were higher than 0.50 μg/μL and the purity (A260/A280) ofthe extracted DNA were higher than 1.5. It closed to the magnitude of the design DNA fragment by agarose gel electrophoresis examining, and corresponded with the test requirement. Mutations at 1 573 fragment of TNFR-II gene were detected in 13 out of 22 keloids. The mutation incidence was 59.1%. Among them, 9 had point mutation at codon 1 663, accounting 40.9%. No TNFR-II gene mutation was detected in all peripheral blood samples. There were significant difference between keloids DNA and peripheral blood DNA (P lt;0.01). The mutations involved point mutation, deletion and insertion as well as multisite and multitype. Conclusion There is a correlation between the mutation at 1 573 fragment of TNFR-II gene and keloid.
ObjectiveTo evaluate effect of RAS gene mutation after liver metastasis resection on overall survival (OS) and disease-free survival (DFS) for patients with colorectal cancer combined with liver metastasis. MethodsA comprehensive and systematic literature search in the PubMed and other databases was conducted, with the final search ending on January 5, 2022. The impact of RAS gene mutation after liver metastasis resection on survival of patients with colorectal cancer combined with liver metastasis was analyzed by the Stata 12.0 software and Review Manager version 5.3 software, meanwhile which were analyzed according to subgroups, including study type (retrospective and prospective studies), region (Asian and European), and number of RAS gene mutation sites (>2 and ≤2). ResultsA total of 26 studies with 13 356 patients were included. The integrated analysis results showed that the patients with RAS mutations had statistically shorter OS [HR=1.54, 95%CI (1.43, 1.65), P<0.001] and DFS [HR=1.32, 95%CI (1.19, 1.44), P<0.001] as compared with RAS wild-type. Except the 1-year overall survival rate, the 2–5-year overall survival rate and 1–5-year disease-free survival rate of patients with RAS gene mutation were statistically lower than those of patients with RAS wild-type (P<0.05). The results of subgroup analysis showed that no matter retrospective and prospective studies, as well as studies in Asian and European countries, it was found that the OS and DFS for patients with RAS gene mutation were shorter than those of patients with wild-type (P<0.05); At the same time, subgroup analysis of the number of RAS gene mutation sites showed that OS and DFS of patients with number of mutation sites >2 were shortened as compared with ≤2 (P<0.05). ConclusionFrom the overall analysis results, the survival of patients with RAS gene mutation after liver metastasis resection is worse than that of patients with RAS wild-type for patients with colorectal cancer combined with liver metastasis.
ObjectiveTo investigate the predicting effect of PIK3CA mutations for the efficacy and prognosis of hepatocellular carcinoma (HCC) patients received surgical resection. MethodsPCR and DNA sequencing were used to detect the PIK3CA mutation status of 79 HCC tissues, its impact on the short and long term effects of the patients were analyzed. ResultsIn this group of patients, mutation rate of PIK3CA gene exon 9 was 39.24% (31/79), PIK3CA mutation rate correlated with lymph node status and tumor differentiation (P < 0.05). The therapeutic effect of patients with PIK3CA mutation was significantly poor than that of the non-mutated group (P < 0.05). The three-year cumulative survival of patients with PIK3CA mutation (33.33%) was significantly lower than non-mutated group's (60.00%) by Kaplan-Meier (P < 0.05). ConclusionPIK3CA gene mutation in exon 9 could impact the efficiency of surgical resection in patients with HCC and could predict a poor survival prognosis.
ObjectiveTo evaluate the diagnostic value of BRAFV600E mutation test in high-risk thyroid nodules with easily underdiagnosed fine-needle aspiration biopsy (FNAB) results.MethodsRetrospectively collected 122 cases of thyroid nodule who treated in the Hebei Petrochina Central Hospital between January 2017 and December 2018, all the cases admitted preoperative ultrasound and FNAB detection. All of the patients had the non-positive cytological results of FNAB and the high-risk features of ultrasound. Contrasted the postoperative pathological coincidence rate of combination of FNAB and BRAFV600E test with FNAB alone.ResultsThe BRAFV600E mutation rate was 27.0% (33/122). The positive rate of BRAFV600E mutation increased with the increase of ultrasound thyroid imaging reporting and data system(TI-RADS) grade (P<0.05), which was independent of patients’ age, gender, number of nodules, diameter of nodules, and FNAB results (P>0.05). The coincidence rate of FNAB combined with BRAFV600E mutation detection was higher than that of FNAB alone ［86.9% (106/122) vs. 69.7% (85/122), P<0.05).ConclusionsThe BRAFV600E mutation test can detect papillary thyroid carcinoma that might be missed by FNAB. We recommend that FNAB should be routinely accompanied by the BRAFV600E mutation test in the high-risk thyroid nodules.
Objective To investigate clinicopathologic features, pathogenesis, and diagnosis and treatment of hereditary pancreatitis (HP). Method The relevant literatures on HP research in recent years were searched and reviewed. Results The HP was similar to the pancreatitis caused by the cholelithiasis, excessive alcohol consumption, hyperlipidemia, etc. in the histomorphology, function, and clinical manifestations and it was difficult to be distinguished. However, HP was different from the other types of chronic pancreatitis due to its early onset, familial, and high risk of pancreatic cancer. The HP was mainly caused by the PRSS1 mutations, and its mutation types mainly included the R122H, N29I, A16V, K23R, etc., among which the R122H and N29I were the two most common types of mutations. There was no specific treatment for the HP. The principles of treatment of HP were similar to the pancreatitist caused by other etiologies, including the nutritional support, blood sugar control, analgesia, etc.. In addition to the medical treatment, the surgical intervention was also the important means for the treatment of HP, including the pancreatic partial resection, total pancreatectomy or total pancreatectomy combined with islet cell autografting. Conclusions HP is an autosomal dominant hereditary disease characterized by recurrent attacks of pancreatitis. Relevant gene tests could be performed for patient with highly suspected HP. It faces great challenges in treatment of HP. Pathogenesis of HP needs to be constantly explored and experimental study of multicenter and large sample needs to be further studied in order to determine its best treatment strategy.