最新刊期
卷 32 ， 期 4 ， 2022
- 摘要：The incidence of renal malignancies is increasing each year. Clear cell renal cell carcinoma (ccRCC) accounts for approximately 80% of all renal malignancies. Its unique genetic background and mutation features involve dysregulation of homeostasis within the tumor microenvironment (TME) represented by pathways such as hypoxic signaling, glycolytic metabolism, amino acid metabolism, and mitochondrial oxidative phosphorylation. Immune checkpoint inhibitor (ICI) in combination with tyrosine kinase inhibitor (TKI) has become the first line of treatment for patients with advanced ccRCC. However, the efficacy of combination therapy has yet to be improved, and there is an urgent need for biomarkers that can assist the diagnosis, treatment, and prognosis. Multi-omics studies have investigated aberrant abnormalities in molecular pathways of ccRCC in recent years. The ccRCC undergoes metabolic reprogramming and prefers inefficient glycolysis as a significant energy source even under normoxia to support unlimited proliferation. In addition, abnormalities in the aerobic glycolytic pathway have been associated with poor prognosis. Dysregulated glycolytic signaling promotes tumor progression and interacts with immune cells within the TME in ccRCC, resulting in an imbalance between pro and antitumor immunity, creating a suppressive immune microenvironment, promoting tumor immune escape, and impairing antitumor effects of immunotherapy. Therefore, integrating the aerobic glycolytic pathway and the immune microenvironment as an entry point, limiting tumor progression by restricting aberrant glycolytic metabolism broadens therapeutic options for ccRCC and pan-cancer treatments. However, further research is required on maximizing the metabolic reprogramming that tumor cells harbor in the complex TME to convert it into a therapeutic target and apply it in clinical practice. Glycolytic inhibitors in combination with ICI or TKI might be a novel strategy that demonstrates synergistic antitumor effects and overcomes resistance in treating human cancers. This review analyzes the correlations between essential rate-limiting enzymes, transporters, glycolytic pathway inhibitors, and the tumor immune microenvironment in ccRCC. Then we summarize the effects of glycolytic inhibitors in human cancers and alterations in the tumor immune microenvironment. Along with the potential clinical translational value in combination with targeted therapy or immunotherapy, targeting glycolysis will provide new insights for the clinical treatment of ccRCC and bring clinical benefits to patients in the future.关键词：Clear cell renal cell carcinoma;Glycolysis;Metabolic reprogramming;Tumor microenvironment;Immunotherapy7163|4384|0更新时间：2025-12-31
Specialists' Commentary
- 摘要：Background and purpose: Gastric cancer is one of the most common malignant tumors of digestive system. Previous study demonstrated that circSMARCA5 was downregulated and could function as a tumor suppressor in gastric cancer. However, the molecular mechanism has not yet been documented. This study aimed to investigate the effects of circSMARCA5 on the proliferation and invasion of gastric cancer cells and their molecular mechanisms. Methods: Cell counting kit-8 (CCK-8) assays and transwell assays were performed to examine the cell proliferative and invasive abilities, respectively. The effect of circSMARCA5 on gastric cancer cell glycolysis was assessed by detecting the extracellular acidification rate, glucose uptake level and lactate production. Real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) assay was performed to detect the expression levels of circSMARCA5, miR-4295 and PTEN. The levels of GLUT1 and LDHA were measured by Western blot assay. The transplanted xenograft model in nude mice was established, and the effects of circSMARCA5 on the tumor growth were observed. Immunohistochemistry assays were performed to examine the expression levels of GLUT1, LDHA and Ki-67 proliferation index in xenograft tumors. Dual luciferase reporter gene assays, Pearson's correlation analysis and RNA immunoprecipitation (RIP) assays were used to confirm the targeting relationship of circSMARCA5 and miR-4295 as well as miR-4295 and PTEN. Results: CircSMARCA5 overexpression inhibited the proliferation and invasion of gastric cancer cells. Compared to the control group, the glycolysis rate, glycolysis capacity, glucose uptake and lactate production in the circSMARCA5-overexpresing group were significantly decreased. In addition, nude mouse transplanted xenograft assays showed that the volume and the weight of the tumors in the circSMARCA5-overexpressing group were lower compared with the control group. Further studies indicated that circSMARCA5 acted as a molecular sponge to inhibit the expression of miR-4295. Besides, miR-4295 could inhibit the expression of PTEN by binding with the 3'-UTR of PTEN mRNA. Rescue experiments by upregulating miR-4295 or downregulating PTEN expression in the circSMARCA5-overexpressing gastric cancer cells were performed, and the results showed that upregulation of miR-4295 or PTEN knockdown could abolish the inhibitory effects of circSMARCA5 overexpression on cell proliferation, invasion and glycolysis. Conclusion: CircSMARCA5 suppresses the proliferation and invasion of gastric cancer cells by targeting miR-4295, increasing the expression level of PTEN and subsequently regulating glycolysis.关键词：Stomach neoplasms;Circular RNA;miR-4295;PTEN;Glycolysis;Invasion1172|1300|0更新时间：2025-12-31
- 摘要：Background and purpose: Nasopharyngeal carcinoma is one of the most common head and neck malignancies in Southeast Asia. Radiotherapy combined with chemotherapy is the main treatment for patients with locally advanced nasopharyngeal carcinoma (LANPC), however, different patients have various levels of clinical benefit. Therefore, early and accurate evaluation of the prognosis of LANPC after radiotherapy and chemotherapy is of great significance for clinical treatment decision-making. This paper aimed to evaluate and compare the value of 18F-Fluorothymidine (FLT) and 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging parameters in predicting the prognosis of patients with LANPC after radiotherapy and chemotherapy. Methods: Patients with LANPC who all received intensity-modulated radiation therapy (IMRT) and neoadjuvant chemotherapy (NACT) in Fudan University Shanghai Cancer Center from May 2012 to January 2015 were retrospectively selected. Clinical follow-up endpoint was progression-free survival (PFS), defined as the time from the beginning of treatment to tumor progression or death from any cause. The focus evaluation was based on the Response Evaluation Criteria in Solid Tumor 1.1 (RECIST 1.1). Pretreatment 18F-FLT and 18F-FDG PET/CT imaging were performed respectively. And the time interval between the two imaging was maintained within 1 week. The main parameters were measured, including maximal standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), proliferative tumor volume (PTV)/metabolic tumor volume (MTV), total lesion thymidine (TLT)/ total lesion glucose (TLG) and tumor heterogeneity index (HI). Spearman rank correlation coefficient was used to analyze the correlation between the above PET/CT parameters and patients with metastasis/recurrence of LANPC. Then, the best cut-off value was determined by the receiver operating characteristic (ROC) curve, and the predictive ability was evaluated by the ROC curve. PFS was evaluated by the Kaplan-Meier method and log-rank test. Results: Among the 24 patients, 6 had metastasis or recurrence. The median follow-up time was 74.51 months. Spearman rank correlation coefficient analysis showed that HI(T-FLT-70%SUVmax) was associated with metastasis or recurrence (P=0.04); ROC curve analysis showed that the sensitivity of HI(T-FLT-70%SUVmax) in predicting metastatic or recurrent nasopharyngeal carcinoma was 80.00%, and the specificity was 79.90% (P=0.043). Survival analysis showed that when HI(T-FLT-70%SUVmax)>0.828, the median PFS was 57.99 months, which was significantly shorter compared with patients with HI(T-FLT-70%SUVmax)0≤0.828 (P=0.014). Conclusion: HI based on 18F-FLT PET/CT may be useful for predicting the prognosis of patients with LANPC receiving radiotherapy and chemotherapy.关键词：PET/CT;Locally advanced nasopharyngeal carcinoma;Predicting;Prognosis36|1660|0更新时间：2025-12-31
- 摘要：Background and purpose: Esophageal cancer is one of the main causes of cancer death in China, and the morbidity and death rates have remained high. Epigenetic acetylation modifications are involved in and regulate the proliferation, invasion and metastasis of a wide variety of tumor cells, and the acetylation modification of tumor proteins mediated by acetyltransferases may be one of the important mechanisms for esophageal carcinogenesis. This study investigated the expression of acetyltransferase 3b (KAT3b) and the ATP-combined box transporter E1 (ABCE1) acetylation level in esophageal cancer and analyzed the correlation and molecular mechanism in the pathogenesis of esophageal cancer. Methods: Fifty-five esophageal cancer tissue samples and 55 para-cancerous mucosal tissues were collected in Affiliated Hospital of Chengde Medical College from January 2020 to May 2021. The protein expressions of ABCE1 and KAT3b were measured by immunohistochemistry and Western blot. The acetylation level of ABCE1and KAT3b protein expression were determined by coimmunoprecipitation (Co-IP). Bioinformatics predicts the acetylation transferase KAT3b undergoing acetylation using ABCE1 as a substrate, and fluorescence immunohistochemistry (IF) verified the location and expressions of ABCE1 and KAT3b in cancerous tissues. The correlation between ABCE1 acetylation and KAT3b and their relationship with the clinical pathology characteristics were analyzed by statistics. RNA interference sequence of KAT3b for downregulation was constructed, and then transfected into esophageal cancer EC109 cells using liposome-mediated methods. The KAT3b mRNA expression and protein levels were determined by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot. ABCE1 protein acetylation levels were detected using Co-IP experiments. Results: Protein expressions of ABCE1 and KAT3b were significantly higher compared with normal esophageal mucosa (P<0.05). The ABCE1 protein was acetylated in esophageal cancer tissue, and the level of ABCE1 protein acetylation was significantly higher in cancer tissues than in normal mucosal tissues (P<0.05). Bioinformatics predicts that the acetyltransferase KAT3b could catalyze the acetylation of ABCE1 as a substrate, and IF confirmed that ABCE1 and KAT3b proteins exhibited a high expression state in cancerous tissues. The ABCE1 acetylation levels and the KAT3b expression were correlated in esophageal cancer tissues, and they were correlated positively. ABCE1 acetylation and KAT3b were associated with esophageal cancer stage, tissue differentiation and lymph node metastasis, and were independent of gender and age. The in vitro experiments showed that the expressions of KAT3b mRNA and protein were inhibited after RNA interference of KAT3b in esophageal cancer cells, and the ABCE1 protein acetylation levels were also decreased significantly. Conclusion: There is correlation between KAT3b and ABCE1 protein acetylation in pathogenesis of esophageal cancer. Highly expressed KAT3b may be an important upstream molecule that catalyze acetylation of ABCE1 and have important potential value in the diagnosis and treatment of esophageal cancer.关键词：Acetyltransferase 3b;ATP combined box transporter E1;Acetylation;Esophageal cancer36|1133|0更新时间：2025-12-31
- 摘要：Background and purpose: Both HOTTIP and H19 are members of long non-coding RNA(lncRNA). They have been found to play an important role in the occurrence, development and migration of tumors. This study aimed to investigate the association between single nucleotide polymorphisms (SNP) of HOTTIP rs2067087, H19 rs2839698 and H19 rs2107425 and the risk of cervical lesions of different grades. Methods: The peripheral venous blood and related clinical data of 345 cases of cervical lesions were collected from Nov. 2018 to Dec. 2020 in Yancheng No.1 People's Hospital, including 220 cases of cervical intraepithelial neoplasia (CIN) and 125 cases of cervical cancer (CC). Three hundred and sixty patients without cervical lesions hospitalized during the same period were selected as the control. TaqMan real-time fluorescence quantitative polymerase chain reaction (RTFQPCR) was used to genotype the HOTTIP SNP rs2067087, H19 SNP rs2839698 and rs2107425 in the two groups, and χ2 test and unconditional logistic regression were used to analyze the association of the three SNP loci with cervical lesions of different grades. Results: Compared with the control group, there were significant differences in genotype distribution of HOTTIP rs2067087 and H19 rs2839698 in patients with cervical lesions. In the recessive model, the frequency of cervical lesions in patients with HOTTIP rs2067087 GG genotype increased by 52.2% (95% CI: 1.021-2.269, P<0.05). Stratified analysis showed that GG genotype at this locus mainly increased the risk of CIN (OR =1.730, 95% CI: 1.117-2.680, P<0.05); Stratified analysis showed that the GG genotype at this locus mainly increased the risk of CIN (OR=1.730, 95% CI:1.117-2.680, P<0.05). Compared with CC+CT genotype, the risk of cervical cancer in patients with H19 rs2839698 TT genotype was reduced by 70.8% (95% CI: 0.087-0.976, P<0.05). No correlation was found between H19 rs2107425 and cervical lesions of different grades (P>0.05). Conclusion: HOTTIP rs2067087 SNP is associated with different levels of cervical lesions, and the GG genotype may be a risk factor for CIN; H19 rs2839698 SNP is associated with the risk of cervical cancer, and the TT genotype may be a protective factor for cervical cancer.关键词：Cervical lesions;Cervical cancer;HOTTIP;H19;Single nucleotide polymorphism;Association33|1446|0更新时间：2025-12-31
Article
- 摘要：With the development of neoadjuvant therapy, the pathological complete response rate has significantly increased for breast cancer patients.Theoretically, the use of locoregional radiotherapy instead of surgery is available for patients with pathological complete response, thus it is essential to predict pathological complete response precisely before surgery. Due to its higher accuracy for assessing the pathological complete response, the second biopsy after neoadjuvant chemotherapy is believed to have potential for diagnosing pathological complete response instead of surgery. Recently several published prospective trials showed the relatively high false negative rates of the second biopsy and omitting surgery for the exceptional responders to neoadjuvant chemotherapy required further investigation. This review elaborated on the clinical utility and significance of the second biopsy firstly and divided these studies into small feasible research and large prospective research in which the results and features were discussed.关键词：Breast cancer;Neoadjuvant therapy;Pathological complete response;Second biopsy4887|2589|0更新时间：2025-12-31
- 摘要：Non-small cell lung cancer (NSCLC) accounts for 80%-85% of lung cancer and is one of the malignant tumors that seriously endanger human health. Treatment of early NSCLC is based on surgical excision or stereotactic body radiation therapy. Whether there is regional lymphatic metastasis when diagnosis is confirmed will affect the choice of local treatment, and whether there is still a risk of lymphatic and hematologic metastasis after the completion of local therapy will be the basis for accurate decision of adjuvant therapy. How to predict the risk of lymphatic or hematologic metastasis of NSCLC remains a challenge. With the development of tumor and the plasticity of treatment, heterogeneity of biological characteristics of tumors in time and space seriously affects the accuracy of clinical diagnosis, treatment and prognostic prediction. Due to the heterogeneity of tumor, it is difficult for invasive biopsy to show the full picture of tumor biological characteristics as a gold standard, which promotes clinical attention to non-invasive methods, such as medical images, to identify biological features. The method to identify tumor biological features based on medical images experiences from the qualitative analysis of artificial visuals to the modeling of advanced statistical methods for manual extraction of imaging features, and then to the application of radiomics and deep learning models, which provide new possibilities for accurate and efficient medical imaging analysis. Based on chest computed tomography (CT) imaging, this paper summarized the progress of research on the prediction of risk of lymphatic and hematologic metastasis, an important factor affecting early NSCLC treatment decision-making.关键词：Non-small cell lung cancer;Radiomics;Deep learning;Lymphatic metastasis;Hematologic metastasis1019|3019|0更新时间：2025-12-31
Review
- 关键词：Integrin β3;Lung adenocarcinoma;Bone metastasis;Exosomes97|1593|0更新时间：2025-12-31
- 关键词：Cerebellar metastasis;Surgery;KI-67 index;Survival analysis;Prognostic factors97|1340|0更新时间：2025-12-31
Short Article
- 摘要：Between April 2020 and November 2021, the Chinese Breast Cancer Society developed practice guideline on screening and early diagnosis of breast cancer in China, which was adapted from European Commission Initiative on Breast Cancer with GRADE approach. This practice guideline includes 50 recommendations and 5 expert consensus statements, with a scope of screening, early diagnosis, genetic testing on recurrence risk, and communication and training in the screening program. The formulation of recommendations considered best available evidence-based medicine, sense of worth and preferences of Chinese women, and cost and resource utilization. The implementation of recommended screening and diagnostic strategies need to consider the local contexts.关键词：Breast cancer;Screening;Early diagnosis;Guideline14371|4585|0更新时间：2025-12-31
Guideline and Consensus
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