Patients with oncogenic driver alterations of non-small cell lung cancer (NSCLC) can benefit from targeted therapy, but acquired resistance is inevitable ultimately. Epigenetic modifications, including DNA methylation, histone modifications, non-coding RNA-mediated regulate and chromatin remodeling, are important mechanisms of acquired resistance in targeted therapy of NSCLC. In recent years, studies have found that epigenetic modifications can effectively reverse drug resistance. Targeted therapy combined with epigenetic modifications may become a promising therapeutic strategy. Here, we review the progress of epigenetic mechanism in acquired resistance of targeted therapy in NSCLC, hoping to provide ideas for screening dominant population and overcoming resistance.
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Objective: To analyze the difference of somatic mutation of DNA mismatch repair (MMR) protein deletion (dMMR) /integrity (pMMR) in colorectal cancer (CRC). Methods: A total of 93 cases of paraffin pathological tissue derived from CRC patients underwent surgical treatment and postoperative routine immunohistochemical diagnosed as dMMR in the Second Affiliated Hospital of Zhejiang University Medical College from January 2015 to January 2017 were collected and conducted the second-generation sequencing test. The expressions of 4 MMR proteins (MLH1, MSH2, MSH6 and PMS2) in CRC tissue were detected by immunohistochemistry method, and the immunohistochemistry results were re-interpreted according to the American Association of Pathologists (CAP) standard. Second-generation sequencing technology was used to detect somatic mutations of 41 genes in 93 cases of paraffin pathological CRC tissue, and Fisher's exact test was used to analyze the gene mutation differences between groups. Results: After re-evaluation according to CAP standard, 31 cases were divided into pMMR group and 62 cases in dMMR group among the 93 CRC patients. The medium number of gene mutations in the dMMR group was 9.5, higher than 3.0 of the pMMR group (P<0.001). Somatic mutation differences were found in 17 genes between the dMMR and pMMR groups, including breast cancer susceptibility genes 1 (BRCA1), BRCA2, MLH1, PDGFRA, PIK3CA, APC, ATM, KIT, MET, PMS2, MSH6, POLE, MSH2, PTCH1, epidermal growth factor receptors (EGFR), TP53 and ERBB2 genes. The pathogenic somatic mutation rates of BRAF, MLH1, MSH2 and MSH6 in the dMMR group were higher than those in the pMMR group [21.0% (13/62) vs 9.7% (3/31), 9.7% (6/62) vs 0 (0/31), 21.0% (13/62) vs 0 (0/31), 22.6% (14/62) vs 0 (0/31), P<0.05]. The mutation rate differences of BLM N515fs, BRAF V600E, PTCH1 R1308fs and KRAS G13D sites were statistically different between the dMMR group and the pMMR group [22.6% (14/62) vs 0 (0/31), 19.4% (12/62) vs 3.2% (1/31), 11.3% (7/62) vs 0 (0/31), 16.1% (10/62) vs 3.2% (1/31), P<0.05]. The mutation rates of 3 uncommon sites including BLM N515fs, MSH6 F1088fs and PTCH1 R1308fs were 28.2% (11/39), 15.4% (6/39) and 15.4% (6/39) in patients with dMMR who were missing MLH1 and PMS2 together, statistically different from all of 0 (0/31) in pMMR patients (P<0.05). Conclusions: CRC Patients with dMMR have more related gene somatic mutations. The BRAF V600E mutation is closely related to dMMR. KRAS G13D, BLM N515fs and PTCH1 R1308fs mutation sites are also associated with the expression of MMR proteins.

Objective: To explore the risk factors for regional lymph node (RLN) metastasis in colorectal cancer patients with mismatch repair deficiency (dMMR). Methods: The data of 357 dMMR colorectal cancer patients who underwent surgery in National Cancer Center from January 2012 to December 2016 was retrospectively analyzed. Univariate and multivariate analysis were used to identify the risk factors for RLN metastasis. Results: Among the 357 patients, 204 were male and 153 were female, 61.6% (220/357) lesion located in right half colon, while the other 16.2% (58/357) located in rectum. Univariate analysis showed that tumor size, differentiation, lymphovascular invasion, tumor deposit, postoperative pathologic T stage (pT), the number of negative lymph nodes and the expression of the MSH6 protein were significantly associated with RLN metastasis (P<0.05). All of the patients with well differentiation tumors (15 patients) or staged pT1 (13 patients) had no RLN metastasis. Multivariate analysis showed that tumor differentiation (OR=2.582, 95%CI=1.567-4.274, P<0.001), pT (OR=3.778, 95%CI=1.448-12.960, P=0.015) and the expression of MSH6 protein (OR=2.188, 95%CI=1.159-4.401, P=0.021) were independent risk factors for RLN metastasis. Conclusions: The postoperative pT stage, tumor differentiation and the expression of MSH6 protein are independent risk factors for RLN metastasis of dMMR colorectal cancer. Preoperative assessment of these factors may further improve the accuracy of predicting the risk of RLN metastasis.

Objective: To investigate the mechanism of tripartite motif-containing 27 (TRIM27) expression promoting inflammatory response in non-small lung cancer cells. Methods: Ten cases of lung cancer tissues and their matched normal tissue (the distance was 5 cm of the tumor marginal) from patients underwent resection in the People's Hospital of Pingyang Hospital Affiliated to Wenzhou Medical University were collected. The expression of TRIM27 was identified by using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. TRIM27 knockdown experiment included negative control (NC(TRIM27)) group, TRIM27 short interfering RNA (siRNA) group, NC(TRIM27)+ TNF-α group and TRIM27 siRNA+ TNF-α group. Interlukin-6 (IL-6) knockdown experiment included NC(IL-6) group and IL-6 siRNA group. The protein expressions of TRIM27, TNFR1, TNFR2 and some TNFR related inflammation factors were verified by qRT-PCR and WB. Results: The expression levels of TRIM27 in NSCLC tissues of different stages (stage Ⅰ: 2.81±0.58, stage Ⅱ: 3.32±1.38, stage Ⅲ: 3.67±1.24) was higher than that in the adjacent normal tissues (1.01±0.15, 0.92±0.10 and 1.05±0.12, P<0.05). The expression levels of TRIM27 mRNA in NC(TRIM27) group and NC(TRIM27)+ TNF-α group were 0.94±0.12 and 1.67±0.03, and the expression levels of TRIM27 protein were 0.31±0.02 and 0.38±0.01, respectively (P<0.05). The expression levels of IL-6 mRNA in NC(TRIM27)+ TNF-α group and TRIM27 siRNA+ TNF-α group were 11.35±0.12 and 5.62±0.15, respectively, and the expression levels of VCAM-1 mRNA were 18.75±0.17 and 9.35±0.11, respectively. STAT3 mRNA expression levels were 16.54±0.10 and 8.12±0.10, respectively, with statistical significance (P<0.05). The expression levels of IL-6 mRNA in NC(IL-6) group and IL-6 siRNA group were 1.10±0.07 and 0.52±0.16, respectively, and the expression levels of STAT3 mRNA were 1.01±0.01 and 0.48±0.12, respectively. The expression levels of TRIM27 mRNA were 1.03±0.01 and 0.30±0.11, respectively, with statistical significance (P<0.05). Conclusion: The upregulation of TRIM27 in NSCLC tissue and cells promotes the expression of TNF-α, and may activate inflammatory response by regulating TNF-α-induced IL-6/STAT3 signaling pathway.

Objective: To explore the effect of circBIRC6 on cisplatin resistance of ovarian cancer cells and the molecular mechanism. Methods: The ovarian cancer cell line SKOV3 and ovarian cancer cisplatin-resistant cell line SKOV3 / DDP were cultured in vitro, and treated with different concentrations of cisplatin. SKOV3 and SKOV3/DDP cells were transfected with si-NC, si-circBIRC6, si-circBIRC6+ anti-miR-NC, si-circBIRC6+ anti-miR-367-3p by liposome-mediated method, which were denoted as DDP+ si-NC group, DDP+ si-circBIRC6 group, DDP+ si-circBIRC6+ anti-miR-NC group and DDP+ si-circBIRC6+ anti-miR-367-3p group, respectively, and then were treated with 2 μg/ml cisplatin for 24 hours. The cell proliferation inhibition rate was detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide method, and the half inhibitory concentration (IC(50)) value of cisplatin was calculated. Real-time fluorescent quantitative polymerase chain reaction was used to detect the transcriptional levels of circBIRC6 and miR-367-3p. Flow cytometry was used to detect the apoptotic rate. Dual luciferase report experiment verified the targeting relationship of circBIRC6 and miR-367-3p. Western blot was used to detect the expressions of Cyclin D1, Bcl-2, p21, Bax. Results: The expression levels of circBIRC6 in SKOV3 cells were 1.00±0.05, significantly lower than 3.04±0.24 in SKOV3/DDP cells (P<0.001). The expression levels of miR-367-3p in SKOV3 cells were 1.00±0.08, significantly higher than 0.54±0.05 in SKOV3/DDP cells (P<0.001). The cell proliferation inhibition rates of SKOV3 cells and SKOV3/DDP cells were (22.47±2.04)% and (8.84±0.71)%, the IC(50) values of SKOV3 cells and SKOV3/DDP cells were 6.65±0.94 and 28.18±4.91, respectively, with significant difference (P<0.05). The proliferation inhibition rate and apoptosis rate of SKOV3 cells in DDP+ si-NC group[(22.19±2.19)% and (10.98±1.12)%] were lower than those in DDP+ si-circBIRC6 group [(74.18±5.36)% and (32.91±3.19)%, all P<0.05]. The proliferation inhibition rate and apoptosis rate of SKOV3/DDP cells[(8.71±0.87)% and (7.39±0.63)%] were lower than those of DDP+ si-circBIRC6 group [(40.85±4.07)% and (25.31±2.53)%, all P<0.05]. The protein expression levels of Cyclin D1 and Bcl-2 in SKOV3 and SKOV3/DDP cells in DDP+ si-circBIRC6 group were lower than those in DDP+ si-NC group, and the protein expression levels of p21 and Bax were higher than those in DDP+ si-NC group (all P<0.05). The dual luciferase report experiment confirmed that circBIRC6 targeted miR-367-3p. Inhibition of miR-367-3p expression reduced the effect of circBIRC6 deletion on ovarian cancer cell proliferation, apoptosis and cisplatin resistance. Conclusion: Knockdown of circBIRC6 may inhibit the proliferation of ovarian cancer cisplatin-resistant cells and induce apoptosis by up-regulating the expression of miR-367-3p, therefore impair the cisplatin resistance of these cells.

Objective: To investigate the effects of tumor protein translation control antisense RNA1 (TPT1-AS1) on the radiosensitivity, cell proliferation, migration and invasion of hepatocellular carcinoma cells by targeting microRNA-30c-5p (miR-30c-5p). Methods: Thirty-four cases of liver cancer tissues and adjacent normal tissues were derived from liver cancer patients who were admitted to Shanxi Provincial People's Hospital from March 2016 to March 2018. Liver cancer HepG2 cell was transfected with negative control siRNA (si-NC group), si-TPT1-AS1 (si-TPT1-AS1 group), pcDNA3.1 (pcDNA3.1 group), pcDNA3.1-TPT1-AS1 (pcDNA3.1-TPT1-AS1 group), si-TPT1-AS1 and anti-miR-NC (si-TPT1-AS1+ anti-miR-NC group), si-TPT1-AS1 and anti-miR-30c-5p (si-TPT1-AS1+ anti-miR-30c-5p group), respectively. Real-time quantitative reverse transcription polymerase chain reaction (qPCR) was used to detect the transcription levels of TPT1-AS1 and miR-30c-5p in normal tissues adjacent to cancer and liver cancer tissues, the clone formation test was used to test the radiosensitivity of HepG2 cells, and the Methyl Thiazolyl Tetrazolium (MTT) test was used to test the proliferation of HepG2 cells. Cell cycle distribution was detected by flow cytometry, Transwell array was used to detect the migration and invasion ability of HepG2 cells, dual luciferase reporter array was used to verify the targeting relationship of TPT1-AS1 and miR-30c-5p, western blot was used to detect the expressions of proliferation, migration and invasion-related proteins. Results: The expression levels of TPT1-AS1 and miR-30c-5p in liver cancer tissues were 0.84±0.08 and 0.13±0.01, statistically different from 0.31±0.03 and 0.50±0.05 in normal tissues adjacent to cancer (P<0.05). When the cells were treated with 2, 4, 6, 8 Gy irradiation, the cell survival scores of the si-TPT1-AS1 group were 0.280±0.040, 0.069±0.011, 0.020±0.003 and 0.005±0.001, respectively, lower than 0.648±0.070, 0.348±0.080, 0.130±0.020 and 0.060±0.009 of the si-NC group (P<0.05), the radiosensitization ratio of the si-TPT1-AS1 group was 1.672. The number of cell migration and invasion in the si-TPT1-AS1 group were (50.00±4.36) and (44.00±4.03), respectively, which were lower than (109.00±8.68) and (94.00±7.49) in the si-NC group (P<0.05), the cell absorbance (A) values at 24, 48 and 72 hours were 0.28±0.03, 0.43±0.04 and 0.68±0.07, respectively, lower than 0.46±0.04, 0.87±0.08 and 1.35±0.13 of the si-NC group (P<0.05), the protein expression levels of Cyclin D1, p21, E-cadherin and MMP-2 were 0.25±0.02, 0.65±0.06, 0.68±0.07 and 0.27±0.03, respectively, statistically different from 0.88±0.08, 0.17±0.02, 0.14±0.01 and 0.89±0.09 of si-NC group (P<0.05), the proportions of S phase and G(2) phase in the si-TPT1-AS1 group were (17.82±1.03)% and (34.15±2.29)%, respectively, significantly different from (35.14±2.61)% and (16.84±1.21)% in the si-NC group (P<0.05). The luciferase activity of cells in the WT-TPT1-AS1+ miR-30c-5p group was 0.26±0.02, lower than 0.92±0.09 in the WT-TPT1-AS1+ miR-NC group (P<0.05). The cell survival scores in the si-TPT1-AS1+ anti-miR-30c-5p group were 0.450±0.081, 0.200+ 0.045, 0.070±0.010, 0.026±0.004 after treatment with 2, 4, 6, 8 Gy irradiation, higher than 0.285±0.043, 0.075±0.014, 0.028±0.004, 0.006±0.001 of si-TPT1-AS1+ anti-miR-NC group (P<0.05). The radiosensitization ratio of the si-TPT1-AS1+ anti-miR-30c-5p group was 0.694. The number of migration and invasion in the si-TPT1-AS1+ anti-miR-30c-5p group were 79.00±6.65 and 68.00±6.33, higher than (52.00±4.41) and (46.00±4.06) of si-TPT1-AS1+ anti-miR-NC Group (P<0.05), the A values at 24, 48 and 72 hours were 0.37±0.03, 0.64±0.06 and 0.96±0.09, respectively, higher than 0.26±0.03, 0.41±0.04, and 0.65±0.06 of si-TPT1-AS1+ anti-miR-NC group (P<0.05), the expression levels of Cyclin D1, p21, E-cadherin and MMP-2 protein were 0.57±0.06, 0.43±0.04, 0.43±0.04 and 0.64±0.06, statistically different from 0.24±0.02, 0.66±0.06, 0.65±0.06 and 0.28±0.03 of the si-TPT1-AS1+ anti-miR-NC group (P<0.05). Conclusions: The expression of TPT1-AS1 up-regulates in the liver cancer tissues. TPT1-AS1 may down-regulate miR-30c-5p expression, reduce the radiosensitivity of liver cancer cells, and promote the proliferation, migration and invasion of liver cancer cells.

Human epidermal growth factor receptor 2 (HER-2) plays an important role in carcinogenesis and development of urothelial carcinoma. Overexpression of HER-2 is associated with poor prognosis of urothelial carcinoma. Although there is no significant benefit from anti-HER-2 targeted therapies of monoclonal antibody and tyrosine kinase inhibitor, Anti-HER-2 antibody-drug conjugate (HER-2-ADC) has shown a promising efficacy in urothelial carcinoma patients with HER-2 overexpression. Therefore, effectively screening the potential beneficiaries of HER-2-ADC drugs has become a new challenge. However, standardized HER-2 scoring system for urothelial carcinoma has yet to be developed. Thus, the Committees organized experts to reach this expert consensus based on the clinical practice of HER-2 expression, gene amplification and mutation testing in urothelial carcinoma, combined with the current research progress and internal discussion of committee members, in order to construct HER-2 testing standard of urothelial carcinoma and improve the accuracy of interpretation, to guide the clinical application.

Objective: To compare clinical characteristics of sporadic gastrinoma and multiple endocrine neoplasia type 1 (MEN1)-related gastrinoma. Methods: A retrospective cohort study was conducted. Patients with clinical manifestations of Zollinger-Ellison syndrome, pathological diagnosis as neuroendocrine neoplasm (NEN) and complete clinical and follow-up data were enrolled. Patients with only high gastric acid secretion but without evidence of NEN, or with other concurrent non-NEN tumors were excluded. According to the above criteria, the clinicopathological data of 52 cases of gastrinoma diagnosed from April 2003 to December 2020 in the First Affiliated Hospital, Sun Yat-sen University, were collected. Patients who met the diagnostic criteria of gastrinoma and met one of the following conditions were diagnosed as MEN1-related gastrinoma: (1) the presence of pathogenic mutations in the MEN1 gene confirmed by genetic testing; (2) NENs involving two or more endocrine glands, namely, pituitary, parathyroid, thymic, pancreatic, and adrenal NENs; (3) NEN and at least one first-degree relatives diagnosed as MEN1. The remaining gastrinomas were defined as sporadic gastrinoma. Student's t test and chi-square test were used for statistical analysis. Clinicopathological characteristics, endoscopic findings, imaging characteristics, treatment, and prognosis of sporadic and MEN1-related gastrinoma were compared. Results: Among 52 patients with gastrinoma, 33 were sporadic gastrinoma and 19 were MEN1-related gastrinoma. The common symptoms of both sporadic and MEN1-related gastrinomas were diarrhea (24/33, 72.7%; 17/19, 89.5%) and abdominal pain (19/33, 57.6%; 9/19, 47.4%). Compared with sporadic gastrinoma, MEN1-related gastrinoma needed longer time for diagnosis [(7.4±4.9) years vs. (3.9±5.2) years, t=-2.355, P=0.022), were more likely multiple tumors [47.4% (9/19) vs. 15.2% (5/33), χ(2)=6.361, P=0.012], had smaller diameter [(1.7±1.0) cm vs. (3.1±1.8) cm, t=2.942, P=0.005), presented the lower tumor grade [G1: 83.3% (15/18) vs. 39.4% (13/33); G2: 11.1% (2/18) vs. 54.5% (18/33); G3: 5.6% (1/18) vs. 6.1% (2/33), Z=-2.766, P=0.006], were less likely to have serum gastrin which was 10 times higher than normal [11.8% (2/17) vs. 56.0% (14/33), χ(2)=8.396, P=0.004], had higher probability of complication with type 2 gastric neuroendocrine tumors (g-NET) [31.6% (6/19) vs. 3.0%(1/33), χ(2)=6.163, P=0.013], and had lower rate of liver metastasis [21.1% (4/19) vs. 51.5% (17/33), χ(2)=4.648, P=0.031). There was no obvious difference between sporadic gastrinomas and MEN1-related gastrinomas in endoscopic findings. Both types presented enlarged and swollen gastric mucosa under the stimulation of high gastric acid, and multiple ulcers in the stomach and duodenum could be seen. Gastrinoma with type 2 g-NET presented multiple polypoid raised lesions in the fundus and body of the stomach. (68)Ga-SSR-PET/CT scan had a 100% detection rate for both types while (18)F-FDG-PET/CT scan had a higher detection rate for sporadic gastrinoma compared with MEN1-related gastrinoma [57.9% (11/19) vs. 20.0% (3/15), χ(2)=4.970, P=0.026]. Among the patients with sporadic gastrinoma, 19 received surgical treatment, 1 underwent endoscopic submucosal dissection, 8 underwent transcatheter arterial embolization (TAE), and 5 underwent surgery combined with TAE. Among patients with MEN1-related gastrinoma, 13 received surgical treatment, and the other 6 received conservative treatment. The median follow-up of all the patients was 21.5 (1-129) months, and the 5-year survival rate was 88.4%. The 5-year survival rate of patients with sporadic and MEN1-related gastrinomas was 89.5% and 80.0% respectively (P=0.949). The 5-year survival rate of patients with and without liver metastasis was 76.2% vs. 100%, respectively (P=0.061). Conclusions: Compared with sporadic gastrinoma, MEN1-related gastrinoma has longer diagnosis delay, smaller tumor diameter, lower tumor grading, lower risk of liver metastasis, and is more likely to complicate with type 2 g-NET, while there is no difference in survival between the two tumor types.

With the development of diagnostic techniques and the improvement of people's living standards, the detection rate of neuroendocrine tumor has been increasing and people are paying more and more attention to it. With multiple treatment modalities, the clinical research progress of neuroendocrine tumor is remarkable. However, due to the tumor heterogeneity, metastasis and recurrence of neuroendocrine tumor remains a difficult problem for clinicians. The efficacy of neuroendocrine tumor still needs to be improved. Therefore, the biological behavior of neuroendocrine tumor needs to be further studied. In recent years, with the development of molecular biology, the basic and transformation research of neuroendocrine tumor has made some progress. In this paper, we focus on the hot topics of neuroendocrine tumor, such as multiomics (copy number variation, genomics, transcriptomics), tumor microenvironment (immune microenvironment, tumor microvasculature, tumor-associated fibroblasts, etc.), preclinical research model construction (cell lines, organoids, patient derived xenograft models, genetically engineered mice), etc. Specifically, the related clinical transformation significance will be elaborated.

Objective To investigate the effect of curcumin combined with 5-FU on autophagy and Yes-associated protein (YAP) expression in hepatocellular carcinoma cells. Methods HepG2 cells, HepG2 cells with stable YAP overexpression, and HepG2 cells with stable YAP knockdown were treated with 10 μmol/L of curcumin and 10 μg/mL of 5-FU alone and in combination for 24 hours. The proliferation of cells was detected by MTT assay. The expression changes of autophagy markers microtubule-associated protein LC3II and YAP were detected by Western blotting. Results When the two agents were used in combination, the inhibition rate of tumor cell proliferation was significantly higher than that of each single agent group. Compared with the control group, group with curcumin, group with 5-FU, and combination group could increase the expression level of LC3II protein and decrease that of YAP in HepG2 cells, HepG2 cells with stable YAP overexpression, and HepG2 cells with stable YAP knockdown. Conclusion The combination of curcumin and 5-FU induces autophagy and down-regulates the expression of YAP in hepatocellular carcinoma cells.

Objectives To study the effect of overexpression of CD47 on apoptosis of human colon cancer SW480 cells and its underlying mechanism. Methods The expression of CD47 in thirty-four tumors was analyzed, along with its correlation to immune cell infiltration, apoptosis, adhesion and angiogenesis in colon cancer by referring to the TCGA database. Meanwhile we packaged an lentivirus vector expressing CD47 and successfully transfected SW480 cells with this vector to stably express CD47. These cells were divided into blank control group, empty body virus infection group and CD47 overexpression group, and then used for the following assays. The infection efficiency was detected by fluorescence microscope and Western blot analysis; the apoptosis rate was detected by flow cytometry; the expression of FasL, caspase-8 and caspase-3 was detected by Western blot analysis. Results The TCGA database analysis showed that CD47 was overexpressed in a variety of tumors, including colon cancer. The mRNA level of CD47 was related to the infiltration of CD4+ T cells, CD8+ T cells, B cells, macrophages and neutrophils in the colon cancer microenvironment. The expression of CD47 involved in biological processes such as apoptosis, adhesion and angiogenesis. Furthermore, the protein-protein interaction network suggested that CD47 interacted with proteins related to death receptor pathway. The apoptosis rate of SW480 cells and the expression of FasL, Caspase-8 and caspase-3 protein in overexpressing CD47 group was significantly higher than the blank control group and empty vector virus infection group. Conclusion The CD47 is highly expressed and is associated with immune cell infiltration in colon cancer. Overexpression of CD47 may inhibit apoptosis by blocking Fas/FasL pathway in human colon cancer SW480 cells.

Objective To investigate the effect of miR-148b-3p on the proliferation and autophagy of acute myeloid leukemia (AML) cells and its molecular mechanism. Methods Based on GEO and TCGA databases, the expression of miR-148b-3p in AML cells and its association with clinical prognosis of patients were analyzed with the bioinformatics software. The expression of miR-148b-3p in AML cells was detected by real-time quantitative PCR. The miR-148b-3p mimic and the miR-148b-3p inhibitor were transiently transfected into AML cell lines THP-1 and NB4 by liposome-mediated transfection, respectively. The proliferation of leukemia cells was evaluated by CCK-8 assay and 5-ethynyl-2'-deoxyuridine (EdU) labeling, and the protein levels of Bcl2, Bcl2-associated X protein (BAX), autophagy marker LC3, P62, and autophagy-related gene 14 (ATG14) were detected by Western blotting. The targeted binding of miR-148b-3p to ATG14 was measured by dual-luciferase reporter gene assay, and the effect of miR-148b-3p/ATG14 axis on the phenotype of AML cells was observed in the rescue experiments. Results A decreased expression of miR-148b-3p was found in leukemia blasts of AML patients, and the overall survival rate of AML patients with low expression of miR-148b-3p was significantly lower than that of the control group. Overexpression of miR-148b-3p inhibited THP-1 cells proliferation, promoted their apoptosis, downregulated the LC3II and ATG14 protein levels, and upregulated the P62 protein levels, while inhibiting the expression of miR-148b-3p in NB4 cells had the opposite effect. miR-148b-3p significantly reduced the luciferase activity of the wild-type ATG14 expression vector. The results of rescue experiments showed that overexpression of ATG14 reversed the inhibitory effect of miR-148b-3p upregulation on cell proliferation and autophagy, while inhibition of ATG14 expression weakened the promotive effect of miR-148b-3p downregulation on cell phenotype. Conclusion The miR-148b-3p inhibits the in vitro proliferation and autophagy of AML cells by targeting ATG14.

Anaplastic lymphoma kinase (ALK) fusion gene, as a tumor driver gene, was crucial for the occurrence and development of non-small cell lung cancer (NSCLC). Recently, targeted ALK fusion gene has become the main treatment method for ALK-positive NSCLC. The first and second generation ALK inhibitors (ALKi), such as crizotinib, ceritinib, alectinib and ensartinib have been approved in China. However, there was no guidance for the management of ALKi adverse reactions. Therefore, this "Recommendations from experts in the management of adverse reactions to ALK inhibitors (2021 version)" has been summarized, led by Lung Cancer Professional Committee of Sichuan Cancer Society and Sichuan Medical Quality Control Center for Tumor Diseases, to provide practical and feasible strategies for clinical ALKi management specification of adverse reactions.
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To investigate the effects of RNA interference of long noncoding RNA FOXCUT on epithelial mesenchymal transformation and mitochondrial function in nasopharyngeal carcinoma (NPC) cells.

To investigate the effect of overexpression of the oncogenic transcription factor ELF4 on proliferation and apoptosis in human insulinoma cells and explore the underlying mechanism.

To explore the expression characteristics of ELK3 and its role in the occurrence, progression and prognosis of gastric cancer.

To investigate the clinical features and prognosis of acute myeloid leukemia (AML) patients with the mixed lineage leukemia (MLL) gene rearrangements AF6 (MLL-AF6) positive.

Colorectal cancer is one of the malignant tumors with the highest morbidity and mortality in China. With the research of precision medicine concept and tumor-related molecular markers, appropriate detection and application of colorectal cancer-related molecular markers has become an important part of current clinical practice. In order to effectively solve the current clinical problems and improve clinicians' understanding and application of molecular markers on colorectal cancer, the Chinese Society of Clinical Oncology(CSCO) Colorectal Cancer Expert Committee organized experts in related fields to write an expert consensus on molecular markers of colorectal cancer based on recent domestic and international clinical trial and clinical experience. The consensus mainly provides guidance on testing specimens, molecular markers and testing methods, and interpretation of testing results. It aims to provide clinicians with standardized clinical reference for diagnosis and treatment, and standard and effective treatment for patients with colorectal cancer.

Objective: To explore the clinicopathological characteristics and genomic characteristics of four patients with epidermal growth factor receptor(EGFR)-mutated advanced adenocarcinoma transformed into small-cell lung cancer. Methods: Four cases of EGFR-mutated advanced adenocarcinoma of the lung transformed into small-cell lung cancer were studied by clinical data, pathological morphology, immunohistochemistry and gene detection. Result: EGFR-mutated adenocarcinoma of the lung was heterogeneous in clinical and genomic profiles, of ten characterized by RB1, TP53 and PIK3CA mutations. Its transformation into small-cell lung cancer was a particularly aggressive mechanism of drug resistance, but the machanisms were not clear NSE and other tumor indicators had low diagnostic value for transformation. Conclusions: EGFR-mutated adenocarcinoma of the lung transformed into small-cell lung cancer was one of the reasons for EGFR resistance with avery poor prognosis.

Exosome is a kind of biological nano-vesicle with a diameter of about 30-100 nm and is synthesized, secreted, and released in almost all types of body cells. Recent studies have found that exosomes contain a variety of functional proteins, including mRNA and microRNAs (miRNAs) and so on, which play an important role in the process of material transfer and information exchange in cells. In addition, the related-exosomal microRNAs secreted by tumor cells play an important role in regulating theoccurrence, development, invasion and metastasis of tumors and other biological processes.. Therefore, the study of tumor-related exosomal microRNAs will help us to explore the mechanism of tumor progression from the perspective of tumor gene regulation and new tumor markers, which will contribute to the early diagnosis, treatment, disease monitoring and prognosis evaluation.