1.High-throughput Sequencing of MET Mutational Landscape in Cancer Patients and the Value of IHC Screening for Targeted Therapy
Feicheng YANG ; Lixia JIANG ; Ruobing LIU ; Kai YANG ; Yewei LI ; Yi XIONG ; Hao DENG ; Jie HU
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(1):172-181
ObjectiveTo investigate the mutation status of the MET gene in tumor patients, with a focus on its expression in lung cancer tissues and its impact on patient prognosis, providing theoretical basis and potential targets for precise diagnosis and treatment of the tumors. MethodsA total of 1,627 tumor patient samples were collected from January 2021 to September 2025. High-throughput sequencing technology was used to conduct DNA-level gene detection on 137 tumor patients with MET mutations. The distribution of mutation sites in exons and introns, as well as the occurrence frequencies of MET gene amplification and gene fusion were analyzed, with particular attention paid to the mutation frequencies of each exon and the high-frequency variant types. Immunohistochemical staining was performed to analyze the expression levels of c-MET protein in tumor tissues of the 137 patients. Immunohistochemical analysis was conducted on tumor tissues of 9 patients with MET gene exon 14 skipping mutations to study the association between c-MET protein expression and this specific mutation type. RNA sequencing results, immunohistochemical staining data, and follow-up prognosis of lung cancer from the GEPIA2 database and TCGA database were comprehensively analyzed to explore the potential relationship between MET gene expression in tumor tissues and patient prognosis. ResultsAmong 1,627 tumor patients, 137 MET mutation patients were detected, including 93 males with an average age of (66.85±9.61) years and 44 females with an average age of (59.43±11.08) years. Lung cancer was the most common tumor type (117 cases). MET gene expression was lower in breast cancer and glioblastoma multiforme, but higher in lung cancer and colorectal cancer as compared with the expression in normal tissues. Survival analysis showed that patients with high MET gene expression in lung adenocarcinoma had a shorter overall survival time than those with low expression. A total of 961 mutations were detected by next-generation sequencing, including 547 exon mutations and 374 intron mutations. MET gene amplification was found in 13 cases and gene fusion in 27 cases. The highest mutation frequency was in exon 2, followed by exon 5, exon 4, and exon 19. High-frequency variant types included c.2890C>A (p.L964M) on exon 4 and c.3028G>T (p.D1010Y) on exon 5. The c-MET protein expression was closely related to the type of gene mutation. Missense mutations often led to positive or strongly positive c-MET protein expression, while nonsense mutations often resulted in weak or absent c-MET protein expression. Among the 9 patients with MET gene exon 14 skipping mutations, the c-MET protein expression score was mostly 0 - 1, with only 1 case scoring 2. Among the 117 lung cancer patients, the incidence rate was higher in males than in females, and more common among stage Ⅲ-Ⅳ patients than among stage I-Ⅱ patients. Out of the 41 patients treated with surgery + targeted drugs (gutemitinib, savolitinib), 8 cases of recurrence or metastasis were found during follow-up. ConclusionMET gene mutations exhibit specific mutation characteristics in different tumor types, and its expression levels show significant differences between various tumor tissues and normal tissues. It is closely related to the poor prognosis of lung adenocarcinoma patients. We found that c-MET protein expression is closely related to the type of MET gene mutation, especially in patients with MET gene exon 14 skipping mutations, which presents a characteristic expression pattern. This provides an important basis for the preliminary screening using immunohistochemistry in clinical practice.
2.Clinical cure and safe drug withdrawal in chronic hepatitis B
Jieli HU ; Yewei JI ; Pai PENG ; Hui FAN ; Liuyang ZHAO ; Haijun DENG ; Ni TANG ; Ailong HUANG
Chinese Journal of Hepatology 2025;33(6):526-533
With the widespread implementation of immunoprophylaxis strategies, the primary challenge in HBV infection prevention and control in China has shifted to reducing the burden of existing infections. A crucial approach to decreasing the burden of existing infections is to develop the effective treatment methods to achieve clinical or functional cures within a limited treatment duration for infected patients. The existing infections can be divided into two parts: those that are easy to cure and those that are difficult to treat. Patients who meet the current drug withdrawal criteria and at the same time have HBsAg<100 IU/mL following treatment with nucelos(t)ide analogue therapy are the easier one to treat, accounting for about 12% of the total infections, and the remaining 88% are difficult to cure. A necessary step toward clinical cure is pushing the HBsAg levels of patients to <100 IU/mL, but this driving effect must stem from effective immune reconstitution against HBV. Recent prevention and control, certain characteristics and implementation of clinical cure, and the safe drug withdrawal are discussed here to offer new perspectives on issues related to hepatitis B.
3.Clinical cure and safe drug withdrawal in chronic hepatitis B
Jieli HU ; Yewei JI ; Pai PENG ; Hui FAN ; Liuyang ZHAO ; Haijun DENG ; Ni TANG ; Ailong HUANG
Chinese Journal of Hepatology 2025;33(6):526-533
With the widespread implementation of immunoprophylaxis strategies, the primary challenge in HBV infection prevention and control in China has shifted to reducing the burden of existing infections. A crucial approach to decreasing the burden of existing infections is to develop the effective treatment methods to achieve clinical or functional cures within a limited treatment duration for infected patients. The existing infections can be divided into two parts: those that are easy to cure and those that are difficult to treat. Patients who meet the current drug withdrawal criteria and at the same time have HBsAg<100 IU/mL following treatment with nucelos(t)ide analogue therapy are the easier one to treat, accounting for about 12% of the total infections, and the remaining 88% are difficult to cure. A necessary step toward clinical cure is pushing the HBsAg levels of patients to <100 IU/mL, but this driving effect must stem from effective immune reconstitution against HBV. Recent prevention and control, certain characteristics and implementation of clinical cure, and the safe drug withdrawal are discussed here to offer new perspectives on issues related to hepatitis B.
4.Analysis of the disease types of 454 patients with epilepsy in southern Sichuan
Pingping DENG ; Yewei XIAO ; Mei LIU ; Hada S SUSHANT ; Xuntai MA
Journal of Chinese Physician 2019;21(8):1160-1163,1167
Objective To analyze the distribution of disease types of the epilepsy patients in southern Sichuan,and to provide guidances for the clinical diagnosis and treatment of epilepsy.Methods The complete medical records of inpatients with epilepsy in southern Sichuan who were clearly diagnosed in the Affiliated Hospital of Southwest Medical University from August 2014 to July 2017 were collected and sorted,and classified according to the latest revision of the epilepsy disease standard of the International AntiEpilepsy Alliance in 2017,and the distribution of disease types of these patients were statistically analyzed.Results A total of 454 patients with epilepsy were included in the study,with a male to female ratio of 1.54∶ 1,and the average age is (39.38 ±22.38) years.There were 71 patients under 15 years old,139 cases from 15 years old to 40 years old,189 cases from 41 years old to 65 years old,and 55 cases from over 65 years old.The patients in all ages were mainly classified as generalized onset,and the patients with different origins were mainly motor seizures.The focal onset were most common in the patients with epileptiform spasm from 40 days to 14 years old.The patients of generalized onset were mostly tonic-clonic seizures and under 65 years old.And the patients of unknown onset were mainly concentrated in 15-65 years old and mainly epileptic spasms.Conclusions Most of the patients with epilepsy in southern Sichuan are middle-aged and elderly,and the patients of all ages of different origins are mainly motor seizure,and the distribution of disease types of these patients are different.Moreover,the tonic-clonic seizure and epileptiform spasm are the most common types in these patients.
5.Association between genetic variation of kinase insert domain receptor and prognosis in colorectal cancer patients received 5-FU based adjuvant chemotherapy
LI Xiaojie ; ZHANG Shengwei ; WANG Huasheng ; WANG Dong ; MEI Jiazhuan ; DENG Yewei
Chinese Journal of Cancer Biotherapy 2019;26(3):317-322
Objective: To investigate the association between genetic variation of kinase insert domain receptor (KDR) and the prognosis in colorectal cancer (CRC) patients received 5-FU based adjuvant chemotherapy. Methods: The clinical data of 176 CRC patients, who underwent surgical treatment at the Department of Anus and Intestine Surgery, People’s Hospital of Zhengzhou during January 2012 and December 2017, were retrospectively analyzed, and 93 cases of tumor tissues were collected for this study. The genotype of KDR polymorphism locus was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). qPCR was used to detect the expression of KDR mRNAin colorectal cancer tissues. The correlation between the polymorphism genotypes and other variables was analyzed by logistic regression model. The expression of different genotypes of KDR was analyzed by nonparametric test. The relationship between KDR genotype and prognosis of patients was analyzed by Kaplan-Meier survival analysis, and the other variables were adjusted by Cox risk scale model. Results: Of the polymorphisms analyzed, only rs2071559 was of clinical significance. The distribution frequency of KDR rs2071559 in 176 CRC patients was as follows: TT genotype in 95 cases (53.98%), TC genotype in 70 cases (39.77%) and CC genotype in 11 cases (6.25%); the minor allele frequency was 0.26; and the distribution of three genotypes was in accordance with Hardy-Weinberg's Equilibrium (P=0.690). The median disease free survival (mDFS) of patients carrying C allele and wild type TT genotype was 4.4 and 3.2 years, respectively (P<0.05); The median overall survival (mOS) of patients with TC/CC genotype and TT genotype was 5.2 and 4.0 years, respectively (P<0.05). After COX model modification, the effect of TC/CC genotype on mOS was still statistically significant (OR=0.55, P<0.05). The mRNA expression of KDR in cancer tissues of the patients with TC/CC genotypes were significantly lower than those of the wild type TT genotype (P<0.01). Conclusion: The polymorphism of KDR rs2071559 is associated with clinical outcomes in patients with colorectal cancer. KDR rs2071559 may affect the prognosis of colorectal cancer patients by affecting the mRNAexpression of KDR.
6. Typing analysis and detection of HPV for condyloma acuminata tissues of perianal
Zhaojie XU ; Yewei DENG ; Rui LI
Chinese Journal of Experimental and Clinical Virology 2017;31(1):35-37
Objective:
To learn the prevalence of HPV infection and its genotypes distribution in perianal warts, discuss the association between HPV infection and age and gender, and assess the methodology performance of PCR-reverse dot blot(PCR-RDB) to detect HPV.
Methods:
HPV genotypes were detected in 316 paraffin specimens of confirmed or suspected perianal condyloma acuminata(CA) patients, including 58 cases for HPV DNA sequencing.
Results:
The HPV infection rate in 316 patients was 81.6%. The first fifth genotypes of single HPV infection were HPV11, 6, 18, 16 and 33. HPV6+ 11, HPV6+ 11+ 16 and HPV6+ 18 were more common in mixed infection. The highest HPV infection rate was from the males aged below 35 years. Regarding the sequencing result as a gold standard, the sensitivity, specificity and accuracy of PCR-RDB in HPV were 92.31%, 89.47% and 91.38% respectively.
Conclusions
The proportion of HPV crissum infection in young male was quite high, the major pathogenic types were HPV 11, 6, 18, 16 and 33. The PCR-RDB method can meet the needs of clinical diagnosis of HPV.

Result Analysis
Print
Save
E-mail