Lung cancer is a malignant tumor with the highest mortality in the world. The most common pathological type of lung cancer is non-small cell lung cancer (NSCLC). In recent years, immunotherapy has brought about epoch-making changes in the treatment of NSCLC. In particular, immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) have been approved for first-line and second-line treatment in patients with metastatic NSCLC. However, only 15% to 30% of patients with advanced NSCLC can achieve sustained remission and long-term survival from immunotherapy. Therefore, biomarker for predicting the efficacy of immunotherapy is particularly important. This article reviews the relevant literatures on predictive biomarkers for immunotherapy of NSCLC and provides direction for future research.
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As the main type of lung cancer, non-small cell lung cancer (NSCLC) is a common cancer which is characterized by low 5-year survival rate and worse prognosis. Nowadays, some studies show that the low survival rate and worse prognosis are due to the resistance to radiotherapy caused by circRNA. Therefore, to find out the relationship between circRNA and radiotherapy resistance of NSCLC was imoprtant. According to research the relevant literatures, the relationship between circRNA and radiotherapy resistance of NSCLC was explored. CircRNA plays an important role in the invasion, metastasis, proliferation and treatment resistance of NSCLC. The radiation resistance of tumor cells induced by circRNA has become a crucial problem in radiotherapy. CircRNA plays an important role in the radiotherapy resistance of NSCLC.
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Lung cancer is one of the malignant tumors with the highest morbidity and mortality in the world. Immune checkpoint inhibitors (ICIs), including programmed cell death 1 (PD-1) antibody, programmed cell death ligand 1 (PD-L1) antibody, and cytotoxic T lymphocyte associated protein 4 (CTLA-4) antibody. It has brought significant survival benefits to some patients with advanced lung cancer and changed the treatment pattern of advanced lung cancer. Previous studies have shown that the objective response rate of PD-1/PD-L1 antibody in advanced non-small cell lung cancer (NSCLC) is only about 20%. So reliable biomarkers are urgently needed to screen out the potential benefit population of ICIs and improve the clinical response rate. Tumor mutational burden (TMB) is an emerging biomarker of immunotherapy in addition to PD-L1 expression. There is little correlation between PD-L1 expression and TMB in lung cancer. It is estimated that TMB can expand the benefit population of immunotherapy. However, in clinical practice, the detection of TMB, the determination of cut-off value and the clinical guidance strategy are still not standardized. This consensus will give guiding suggestions on the detection and application scenarios of TMB, so as to promote the standardization of TMB application for immunotherapy in lung cancer.
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Objective: To compare the clinical features, clinical efficacy, and prognosis of patients with double-hit and non-double-hit high-risk multiple myeloma (MM) and explored the clinical significance of high-risk cell karyotype in MM development. Methods: The clinical data of 73 high-risk MM patients admitted to the Department of Hematology of Fujian Provincial Hospital from January 2011 to February 2019 were retrospectively analyzed. Interphase fluorescence in situ hybridization was used to detect their karyotypes. Based on mSMART 3.0 risk stratification, we divided the patients into a double-hit group (28 cases) and a non-double-hit group (45 cases). Results: Fifteen patients in the double-hit group and 26 in the non-double-hit group received bortezomib-based chemotherapy. The median progression-free survival (PFS) in the double-hit and the non-double-hit groups was 8.0 months and 22.0 months, and the median overall survival (OS) was 10.0 months and not reached, respectively. Ten patients in the double-hit group and 12 in the non-double-hit group received bortezomib combined with lenalidomide (RVD) chemotherapy. The median PFS in the double-hit group and the non-double-hit group was 12.0 months and 24.0 months, and the median OS was 14.0 months and not reached, correspondingly. Both the PFS and OS of the double-hit group were significantly shorter than those of the non-double-hit group (P<0.05). Univariate analysis results indicated that cytogenetic abnormalities, revised-international staging system (R-ISS), β2 microglobulin, and calcium had significant effects on PFS in high-risk MM patients (P<0.05). The cytogenetic abnormalities, R-ISS, and β2 microglobulin were associated with OS in high-risk MM patients (P=0.001). Multivariate Cox regression analysis showed that the cytogenetic grouping was an independent prognostic factor for OS and PFS in high-risk MM patients. The risk of disease progression was 3.160 times (95% CI: 1.364-7.318) and the risk of death was 2.966 times higher (95%CI: 1.205-7.306) in the double-hit group than those in the non-double-hit group. Calcium was an independent risk factor for PFS in the high-risk MM patients. Notably, the risk of disease progression in patients with calcium levels≥ 2.75 mmol/L was 2.667 times higher than that in patients with calcium<2.75 mmol/L (95% CI: 1.209-5.883). Conclusions: Double-hit patients are a highly specific group with worse high-risk MM prognosis. In such patients, the relapse is more common, the disease progression is faster, and the survival time is shorter than those in the non-double-hit patients.

Objective: To investigate the correlation between UGT1A1 polymorphisms and the irinotecan plus S-1 regimen-induced toxicities in Chinese advanced esophageal squamous cell carcinoma (ESCC) patients. Methods: A total of 46 recurrent or metastatic ESCC patients selected from ESWN 01 trial were randomly assigned to irinotecan plus S-1 group [intravenous infusion of irinotecan (160 mg/m(2)) on day 1 and oral S-1 (80-120 mg) on days 1-10, repeated every 14 days]. Peripheral venous blood at baseline was collected and genomic DNA was extracted. The genetic polymorphisms of UGT1A1*6 and UGT1A1*28 were analyzed by polymerase chain reaction (PCR) amplification. Irinotecan plus S-1 regimen-induced toxicities of patients with different UGT1A1 polymorphisms were observed. The correlation between UGT1A1 polymorphisms and the adverse effects was analyzed. Results: Among the 46 patients, the numbers of UGT1A1*6 wild type genotype (GG), mutant heterozygote (GA) and mutant homozygote (AA) were 30, 15 and 1, while those with UGT1A1*28 wild type genotype (TA6/6), mutant heterozygote (TA6/7) and mutant homozygote (TA7/7) were 36, 8 and 2, respectively. Only one patient with UGT1A1*6 AA genotype occurred grade 3 diarrhea, while one of the 2 patients with UGT1A1*28 TA7/7 genotype occurred grade 4 diarrhea. No neutropenia was observed in the patient with UGT1A1*6 AA genotype, however, both of the two patients with UGT1A1*28 TA7/7 genotype occurred grade 3-4 neutropenia. Patients with UGT1A1*28 genetic polymorphism (TA 6/7 or TA7/7) had a higher response rate compared with wild-type TA6/6 carriers. (55.6% versus 26.5%). Conclusions: The homozygous genotype of UGT1A1*6 AA and UGT1A1*28 TA7/7 are rare (<5%) in Chinese ESCC population. Not all homozygous AA and TA7/7 carriers occur severe dose limited toxicities (DLT) when treated with irinotecan (160 mg/m(2)) plus S-1 regimen for 2 weeks. However, it's still necessary torigorously observe the occurrence of severe diarrhea and neutropenia in patients with UGT1A1*6 AA and UGT1A1*28 TA7/7 and adjust the dose timely.

Objective: To explore the role and molecular mechanism of hepatocyte nuclear factor 4γ (HNF4γ) in proliferation and stemness of gastric cancer. Methods: A total of 102 cases of paraffin-embedded gastric cancer tissues and matched adjacent gastric tissues and 42 cases of fresh-frozen tissues derived from gastric patients who received radical gastrectomy were collected from the First Affiliated Hospital of Zhengzhou University between 2012 to 2015. The expression of HNF4γ was tested by immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR). HNF4γ overexpressed (AGS-HNF4γ) and shRNA silenced (HGC27-shHNF4γ) gastric cell lines were established. The effects of HNF4γ on cell proliferation and stemness were verified by XTT, clone formation and sphere formation assay. The expression of CD44 was detected by western blot. Results: The mRNA expression level of HNF4γ in fresh-frozen gastric cancer tissue was (12.43±2.702), which was significantly higher than (3.639±1.109) in normal tissue (P<0.001). The high protein expression rate of HNF4γ in paraffin-embedded gastric cancer tissues was 41.2% (42/102), which was significantly higher than 8.8% (9/102) in normal gastric mucosa tissue (P< 0.001). The protein expression of HNF4γ was closely related to the tumor differentiation, infiltration depth, lymph node metastasis and tumor stage (P<0.05). The median survival interval of patients with HNF4γ high expression was 25 months, the 3-year survival rate was 4.8% (2/42), significantly lower than 38 months and 51.7% (31/60) of patients with normal HNF4γ expression (P<0.001). The proliferation and CD44 protein expression of AGS-HNF4γ cells were significantly higher than those of the AGS-Vector cells. The number of clone formation, sphere formation rate of AGS-HNF4γ cells were 243.5±24.5 and (83.5±3.9)%, significantly higher than 81.0±16.0 and (21.8±5.6)% of AGS-Vector cells (P=0.030 and P=0.010, respectively). The proliferation and CD44 protein expression of HGC27-shHNF4 cells were significantly lower than those of the HGC27-vector cells. The number of clone formation, sphere formation rate of HGC27-shHNF4 cells were 26.0±1.0 and (20.8±8.4)%, significantly higher than 83.5±4.5 and (72.5±4.8)% of HGC27-vector cells (P=0.006 and P=0.030, respectively). Conclusions: HNF4γ is upregulated in the gastric cancer tissues and related with the poor prognosis of patients with gastric cancer. Overexpression of HNF4γ promotes the proliferation and remains the stemness of gastric cancer cells by upregulating the expression of CD44.

Objective: To investigate the effect of miR-369-3p targeting ACTN4 expression on proliferation and apoptosis of hepatocellular carcinoma cells. Methods: Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were used to detect the expression levels of miR-369-3p and ACTN4 in hepatocarcinoma tissues and adjacent tissues. MiR-369-3p mimics, miR-negative control (NC), si-ACTN4, and si-NC were transfected into hepatocellular carcinoma MHCC97H cells by liposome method. Cell proliferation was detected by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-dipheny-ltetrazolium bromide (MTT) assay. Flow cytometry was used to detect cell cycle and apoptotic rates. The dual luciferase reporter assay was used to verify the targeted regulation of ACTN4 by miR-369-3p. Western blot was used to detect the expressions of cyclin D1, p21, Bcl-2 and Bax. Results: The expression level of miR-369-3p in liver cancer tissue was lower than that in adjacent tissues [(0.46±0.04) vs (1.00±0.08), P<0.001)], while the expression level of ACTN4 was higher than that in adjacent tissues [mRNA (3.12±0.29) vs (1.01±0.09); protein (0.61±0.06) vs (0.25±0.03), P<0.001]. Overexpression of miR-369-3p significantly decreased the cell viability[(0.71±0.06) vs (1.26±0.11), P<0.001)], increased cell apoptosis rate [(20.16±2.11)% vs (6.25±0.64)%, P<0.001], increased the proportion of cells in G(1) phase [(31.14±3.36)% vs (51.56±5.23)%, P<0.001], decreased the proportion of cells in S phase [(32.44±3.56)% vs (14.33) ±1.45)%, P<0.001], increased the levels of p21 and Bax protein (P<0.001), and decreased the levels of cyclin D1 and Bcl-2 protein (P<0.001). Inhibition of the expression of ACTN4 significantly reduced the cell viability [(0.78±0.07) vs (1.24±0.12), P<0.001], increased the apoptosis rate [(6.58±0.66)% vs (18.32±1.82)%, P<0.001], increased the proportion of cells in G(1) phase [(48.69±4.21)% vs (30.33±3.01)%, P<0.001], decreased the proportion of cells in S phase [(36.21±3.42)% vs (18.54±1.61)%, P<0.001], increased the protein levels of p21 and Bax (P<0.001), and decreased the levels of cyclin D1 and Bcl-2 protein (P<0.001). Compared with the miR-369-3p+ pcDNA group, overexpression of ACTN4 increased the proliferation ability of hepatocellular carcinoma MHCC97H cells at 72 hours of culture[(1.12±0.11) vs (0.68±0.06), P<0.001], significantly reduced the proportion of cells in G(1) stage [(38.81±3.24)% vs (51.80±4.57)%, P<0.001], significantly increased the proportion of S-phase cells [(31.65±3.11)% vs (15.69±1.44)%, P<0.001], decreased cell apoptosis rate [(13.86±1.37)% vs (22.69±2.24)%, P<0.001], increased protein expressions of cyclin D1 and Bcl-2 (P<0.001), decreased the protein expressions of p21 and Bax (P<0.001). Conclusion: MiR-369-3p can induce cell cycle arrest in G(1) phase, inhibit the proliferation and promote apoptosis of liver cancer cells by regulating the expression of ACTN4.

Objective: To investigate the effects of lncRNA LINC00839 on the proliferation, migration and invasion of hepatocellular carcinoma cells and its mechanism. Methods: Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of LINC00839 and miR-3666 in hepatocellular carcinoma tissues and adjacent tissues. Pearson correlation was used to analyze the correlation between LINC00839 and miR-3666 expression in liver cancer tissues. Hepatocellular carcinoma cells MHCC97H were cultured in vitro and divided into si-NC group, si-LINC00839 group, miR-NC group, miR-3666 group, si-LINC00839+ anti-miR-NC group, and si-LINC00839+ anti-miR-3666 group. Methylthiazoletrazolium (MTT) method and clone formation experiment were used to detect cell proliferation. Transwell array was used to detect the cell migration and invasion. Western blot was used to detect the protein expressions of p21, E-cadherin and MMP-2. The double luciferase reporter gene experiment was used to verify the regulatory relationship between LINC00839 and miR-3666. Results: Compared with adjacent tissues, the expression level of LINC00839 in hepatocellular carcinoma tissues increased (2.82±0.27 vs. 0.96±0.10, P<0.001), but the expression level of miR-3666 decreased (0.23±0.02 vs. 1.01±0.10, P<0.001). The expression levels of LINC00839 and miR-3666 in liver cancer tissue were negatively correlated (r=-0.658, P<0.001). The survival rate of MHCC97H cells in the si-LINC00839 group [(53.91±5.41)% vs. (100.53±10.22)%], the number of clones formed (92.0±8.0 vs. 164.0±14.3), the number of migration (131.0±12.7 vs. 247.0±22.4), the number of invasion (66.0±6.4 vs. 120.0±11.6) and the protein level of MMP-2 (0.20±0.02 vs. 0.67±0.06) were lower than those in the si-NC group (P<0.001). However, the protein levels of p21 (0.76±0.07 vs. 0.25±0.02) and E-cadherin (0.78±0.08 vs. 0.14±0.01) were higher than those in the si-NC group (P<0.001). LINC00839 targeted and negatively regulated the expression of miR-3666. The survival rate of MHCC97-H cells in the miR-3666 group [(47.93±4.86)% vs. (100.11±10.21)%], the number of clone formation (78.0±7.7 vs. 166.0±15.9), the number of migration (117.0±12.1 vs. 250.0±25.0), the number of invasion (57.0±5.7 vs. 121.0±12.3) and the protein level of MMP-2 (0.16±0.01 vs. 0.69±0.07) were lower than those in the miR-NC group (all P<0.001). However, the protein levels of p21 (0.83±0.08 vs. 0.24±0.02) and E-cadherin (0.87±0.09 vs. 0.13±0.01)were higher than those in the miR-NC group (all P<0.001). The survival rate of MHCC97-H cells in the si-LINC00839+ anti-miR-3666 group [(89.94±9.05)% vs. (54.12±5.39)%], the number of clones (143.0±13.8 vs. 94.0±9.4), the number of migration (208.0±19.8 vs. 129.0±12.6), the number of invasion (108.0±10.1 vs. 65.0±6.4) and the protein level of MMP-2 (0.31±0.03 vs 0.66±0.06) were higher than those in the si-LINC00839+ anti-miR-NC group (P<0.001). However, the protein levels of p21 (0.31±0.03 vs. 0.74±0.07) and E-cadherin (0.28±0.03 vs. 0.80±0.08) were lower than those int the si-LINC00839+ anti-miR-NC group (P<0.001). Conclusion: Inhibition of LINC00839 expression may inhibit the proliferation, migration and invasion of hepatocellular carcinoma cells by targeting up-regulation of miR-3666 expression.

Objective: To explore the clinical features and possible pathogenesis of spontaneous remission of acute myeloid leukemia (AML) . Methods: We retrospectively analyzed the clinical data of a patient with spontaneous remission of AML, MLL-AF9 rearrangement, and abnormal liver function in the First Affiliated Hospital of Zhengzhou University, and the relevant pieces of literature were summarized. Results: The patient experienced lung infection, fever, and liver dysfunction and was treated with anti-infection and blood transfusion. After complete response (CR) , the patient remained in CR with mild, indirect bilirubin elevation at 35 months of follow-up. Additionally, 56 cases of adult AML (non-acute promyelocytic leukemia) were reported in the literature from 1990 to June 2021. The cases were checked by bone marrow aspiration, and our patients were summarized and analyzed. Furthermore, 57 patients, including 37 males and 20 females, with a median age of 51 (20-83) years and a median remission time of five months; 52 patients achieved complete remission. In addition, there were five cases with long-term remission and a chromosomal record, with no recurrence so far, three with normal karyotype and two with t (9;11) (q21;q23) . Conclusion: The spontaneous remission of leukemia is rare and may be related to immunosuppression and genes.

Objective: To investigate the effects of circular RNA (circRNA) BICD2 (circ-BICD2) on glutamine metabolism, cell proliferation, migration, invasion and apoptosis of oral squamous cell carcinoma (OSCC) cells and to further explore the possible mechanism. Methods: OSCC cells were purchased from Shanghai Institute of Cellular Cells, Chinese Academy of Sciences. Samples of OSCC tissues and corresponding adjacent tissues were collected from 35 OSCC patients who underwent surgical resection at the First Affiliated Hospital of Zhengzhou University from January 2016 to January 2018. Real-time quantitative PCR (RT-qPCR) and western blot were performed to detect the expression levels of circ-BICD2, miR-296-5p and transgelin2 (TAGLN2) in OSCC tissues and cells. Bioinformatics, dual luciferase report experiment and RNA immunoprecipitation (RIP) experiment were used to determine the targeting relationship between circ-BICD2 and miR-296-5p, miR-296-5p and TAGLN2. According to different transfection oligonucleotides or plasmids, CAL27 and SCC9 cells were divided into si-NC group (transfection si-NC), si-circ-BICD2 group (transfection si-circ-BICD2), si-circ-BICD2+anti-miR-NC group (transfected with si-circ-BICD2 and anti-miR-NC), si-circ-BICD2+anti-miR-296-5p group (transfected with si-circ-BICD2 and anti-miR-296-5p), miR-NC group (transfected with miR-NC), miR-296-5p group (transfected with miR-296-5p mimic), miR-296-5p+pcDNA (transfected with miR-296-5p mimic and pcDNA) and miR-296-5p+TAGLN2 group (transfected with miR-296-5p mimic and pcDNA-TAGLN2). Cell counting kit 8(CCK-8), colony formation experiment, flow cytometry, Scratch healing test and Transwell experiment were applied to detect OSCC cell viability, number of colonies, cycle distribution, apoptosis rate, migration rate and invasive cell numbers. Glutamine (gln) consumption, α-ketoglutaric acid (α-KG) production and adenosine triphosphate (ATP) concentration were also detected by the kit. The expression of cyclinD1 and Glutamine hydrolase (GLS1) proteins of CAL27 and SCC9 cells in each of the groups were detected by western blot. Twelve four-week-old clean BALB/c female nude mice were injected with a single-cell suspension of SCC9 cells into the axillary skin to establish a transplanted tumor model. Twelve transplanted tumor model mice were divided into sh-circ-BICD2 group and sh-NC group. Mice were sacrificed by cervical dislocation at 32 days after injection, the tumors were removed and the tumor weight was tested. Results: The expressions of circ-BICD2 (2.54±0.74) and TAGLN2 (1.86±0.15) were increased (P<0.05), while the expression of MiR-296-5p was decreased in OSCC tissues (P<0.05). Cell viability, clone formation numbers, migration rate, invasive cell numbers, S phase cell ratio, glu consumption, α-KG production, ATP concentration, expression of cyclinD1 and GLS1 proteins of OSCC cells were significantly reduced after interference with circ-BICD2 expression. The apoptosis rate, the proportion of cells in G0-G1 phase and the expression of miR-296-5p were significantly increased (P<0.05). Inhibiting the expression of miR-296-5p coulld reverse the effect of interfering with circ-BICD2 on OSCC cell proliferation, migration, invasion, apoptosis and glutamine metabolism (P<0.05). After overexpression of miR-296-5p, cell viability, clone formation red number, migration rate, number of invasive cells, S phase cell ratio, glu consumption, α-KG production, ATP concentration and expressions of cyclinD1, GLS1 and TAGLN2 proteins in OSCC cells were significant decrease. The rate of apoptosis and the proportion of cells in G0-G1 phase were significantly increased (P<0.05). Compared with overexpression of miR-296-5p, cell viability, clone formation red number, migration rate, number of invasive cells, S phase cell ratio, glu consumption, α-KG production, ATP concentration, cyclinD1, GLS1 and TAGLN2 proteins in OSCC cells after overexpression of miR-296-5p and TAGLN2 were significantly increased, and the apoptosis rate and the proportion of cells in the G0-G1 phase were significantly decreased (P<0.05). Compared with the sh-NC group, the tumor weights of mice in the sh-circ-BICD2 group were significantly reduced (P<0.05). Conclusions: Circ-BICD2 was highly expressed in OSCC cells. Interfering with circ-BICD2 could inhibit the proliferation, migration and invasion of OSCC cells, glutamine metabolism and tumor growth and promote cell apoptosis, which might be relate to the regulation of miR-296-5p/TAGLN2 molecular axis.

Objective: To explore the effect and possible mechanism of circ_0023990 on the radiosensitivity of thyroid cancer cells. Methods: qRT-PCR was used to detect the expression of circ_0023990 in the cancer tissues of 55 patients with thyroid cancer and thyroid cancer cell lines (TPC-1, KTC-1, FTC-133 and CAL-62), and the relationship between the expression of circ_0023990 in cancer tissues and the clinical characteristics of the patients were analyzed. Thyroid cancer cells TPC-1 and KTC-1 were divided into sh-circ_0023990 group, sh-NC group, sh-circ_0023990+anti-miR-873-5p group, sh-circ_0023990+anti-miR-NC group, miR-873-5p group, miR-NC group, miR-873-5p+pcDNA-ANXA2 group and miR-873-5p+pcDNA group, and then clone formation experiment was used to detect cell radiosensitivity. After each group of cells was irradiated with 4Gy radiation, the expression of γH2AX protein in the cells was detected by Western Blot. The dual luciferase reporter gene experiment verified the targeting relationship between circ_0023990 and miR-873-5p or miR-873-5p and ANXA2. Results: The expression of circ_0023990 in thyroid cancer tissues was higher than that in normal tissues (2.15±0.09 vs. 0.97±0.05, P<0.05), and its expression was closely related to tumor size, lymph node metastasis and TNM staging of patients with thyroid cancer (P<0.05). The expression of circ_0023990 in thyroid cancer cell lines (TPC-1, KTC-1, FTC-133 and CAL-62) were higher than that of normal thyroid cells HTori-3 (3.16±0.38, 2.63±0.28, 1.82±0.24, 1.71±0.22 vs. 1.00±0.10, all P<0.05). The survival scores of TPC-1 and KTC-1 cells in the sh-circ_0023990 group were significantly lower than those in the sh-NC group (P<0.05), and the sensitization ratios were 2.482, 1.643; The survival scores of TPC-1 and KTC-1 cells in the sh-circ_0023990+anti-miR-873-5p group were higher than those in the sh-circ_0023990+anti-miR-NC group (P<0.05), and the sensitization ratios were 0.305, 0.441, respectively. The survival scores of TPC-1 and KTC-1 cells in the miR-873-5p group were lower than those in the miR-NC group (P<0.05), and the sensitization ratios were 2.044, 1.653 respectively. The survival scores of TPC-1 and KTC-1 cells in the miR-873-5p+pcDNA-ANXA2 group was higher than that in the miR-873-5p+pcDNA group (P<0.05), and the sensitization ratios were 0.496, 0.686, respectively. The expression of γH2AX protein in TPC-1 and KTC-1 cells of the 4 Gy+sh-circ_0023990 group were higher than that in the 4 Gy+sh-NC group (2.68±0.27 vs. 1.87±0.25, 2.46±0.19 vs. 1.77±0.14; all P<0.05), but the expression of γH2AX protein in TPC-1 and KTC-1 cells of the 4 Gy+sh-circ_0023990+anti-miR-873-5p group were lower than that in the 4 Gy+sh-circ_0023990+anti-miR-NC group (1.13±0.09 vs. 1.69±0.09, 1.11±0.08 vs. 1.60±0.08; both P<0.05). The expression of γH2AX protein in TPC-1 and KTC-1 cells in the 4 Gy+miR-873-5p group were higher than that in the 4 Gy+miR-NC group (2.35±0.16 vs. 1.84±0.14, 2.26±0.12 vs. 1.77±0.13; both P<0.05), but the expression of γH2AX protein in TPC-1 and KTC-1 cells of the 4 Gy+miR-873-5p+pcDNA-ANXA2 group were lower than that in the 4 Gy+miR-873-5p+pcDNA group (1.96±0.12 vs. 2.41±0.12, 1.92±0.07 vs. 2.28±0.12; both P<0.05). circ_0023990 targeted the negative regulation of miR-873-5p, and ANXA2 was the target gene of miR-873-5p. Conclusion: circ_0023990 was highly expressed in thyroid cancer tissues and cell lines, and it may promote the radiotherapy resistance of thyroid cancer cells in vivo through regulating miR-873-5p/ANXA2 axis.

To explore the role of miR-671-5p in regulating the migration and invasion of osteosarcoma and the underlying mechanisms.

To identify the key genes involved in the transformation of hepatitis B virus (HBV) into hepatocellular carcinoma (HCC) and explore the underlying molecular mechanisms.

To explore the association of methylation levels of C19orf57, MAP9, EMR3, NEK6 and PCOLCE2 genes in peripheral blood with breast cancer (BC) in Chinese women.

Lung cancer ranks the first cancer-related morbidity and mortality in China. Tumor metastasis always predicts the poor prognosis for patients. Moreover, lymphatic metastasis is one of the most significant predictors of poor prognosis in patients with non-small cell lung cancer (NSCLC) and lymphangiogenesis represents the bridge that functionally facilitates tumor lymphatic metastasis. In this review, we first discussed the molecular mechanisms of tumor-associated lymphangiogenesis and the interaction between tumor microenvironment and lymphatic endothelial cells, then, summarized the role of non-coding RNA in regulating tumor-associated lymphangiogenesis in recent frontier studies, with the aim to provide some novel insights on NSCLC-related lymphangiogenesis research, diagnosis and treatment.
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Lung cancer is the most common malignant tumor in the world, among which non-small cell lung cancer (NSCLC) accounts for about 85% of the total number of lung cancers. The 5-year overall survial (OS) of radical surgery NSCLC patients ranged from 92% in stage Ia1 to 26% in stage IIIb, and the continuously decreasing survival time made it a strong clinical need for precise adjuvant therapy to eradicate molecular residual disease (MRD). At present, circulating tumor DNA (ctDNA) as a molecular indicator of MRD has gradually moved from the laboratory to the clinic. The latest consensus proposes that ctDNA with abundance ≥0.02% can be stably detected in the peripheral blood of perioperative NSCLC patients, which is based on the possibility of ctDNA as an MRD indicator. MRD detection technology supports the possibility of monitoring after radical treatment of NSCLC, and ctDNA can predict the recurrence of the disease earlier than the imaging monitoring after treatment of NSCLC, providing valuable time for timely adjustment of adjuvant therapy. In the studies on early postoperative adjuvant therapy of NSCLC, different guidelines differ on whether appropriate adjuvant therapy should be carried out, while MRD can be used as a more accurate predictor to guide postoperative adjuvant therapy, so that patients can benefit from the disease treatment.
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Rearranged during transfection (RET) fusions are found in 0.7% to 2% of non-small cell lung cancer (NSCLC). Fusions between RET gene and other domains represent the distinct biological and clinicopathological subtypes of NSCLC. Recent years have witnessed the remarkable advancement of RET fusion-positive advanced NSCLC therapy. Conventional chemotherapy produced moderate clinical benefits. Prior to the introduction of targeted therapy or in the context of unavailability, platinum-based systemic regimens are initial therapy options. Immunotherapy predicted minimal response in the presence of RET fusions while currently available data have been scarce, and the single-agent immunotherapy or in combination with chemotherapy regimens are not recommended as initial systemic therapy in this population. The repurpose of multi-target kinase inhibitors in patients with RET fusion-positive NSCLC showed encouraging therapeutic activity, with only cabozantinib and vandetanib being recommended as initial or subsequent options under certain circumstances. However, there are still unmet clinical needs. Pralsetinib and selpercatinib have been developed as tyrosine kinase inhibitors (TKI) selectively targeting RET variation of fusions or mutations, and both agents significantly improved the prognosis of patients with RET fusion-positive NSCLC. Pralsetinib and selpercatinib have been established as preferred first-line therapy or subsequent therapy options. As observed with other TKIs treatment, resistance has also been associated with RET targeted inhibition, and the acquired resistance eventually affect the long-term therapeutic effectiveness, leading to limited subsequent treatment options. Therefore, it is essential to identify resistance mechanisms to TKI in RET fusion-positive advanced NSCLC to help reveal and establish new strategies to overcome resistance. Here, we review the advances in the treatment of RET fusion-positive advanced NSCLC.
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The anti-tumor effect of pigment epithelium-derived factor (PEDF) has been widely confirmed. However, the anti-tumor effect of its peptides is rarely reported. This study aims to investigate the effects of PEDF and its peptides on the apoptosis and migration of non-small cell lung cancer (NSCLC).