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2025  Vol. 52  No. 6

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SPECIAL FEATURE
Current Status and Future Prospects of Treatment for EGFR-Positive Non-Small Cell Lung Cancer After Resistance to EGFR-TKI
Abstract:

EGFR-mutant non-small cell lung cancer (NSCLC) is a common type of lung cancer, with EGFR tyrosine kinase inhibitors (EGFR-TKIs) being the standard first-line treatment. However, most patients with NSCLC eventually develop resistance to EGFR-TKIs. Studies on the mechanism underlying EGFR-TKI resistance have driven the development of personalized and precision medicine. Current strategies to address resistance include targeted therapy, immunotherapy, and novel drug treatments. Selecting the appropriate personalized treatment plan is crucial for improving the survival rate and quality of life of patients with EGFR-mutant NSCLC. Thus, this study provides a brief review of the current status and future perspectives in the treatment of EGFR-mutant NSCLC after progression on EGFR-TKI therapy.

Current Status and Future of Multidisciplinary Team in Hepatocellular Carcinoma
Abstract:

Hepatocellular carcinoma (HCC) poses a significant hazard to public health in China because of its high incidence, high mortality, and high rate of advanced stages. Early detection and treatment of HCC by screening for high-risk populations is instrumental for enhancing survival rates among patients with HCC in China. Liver resection, local ablation, interventional therapy, radiotherapy, and drug therapy are all effective treatments for patients with HCC, and appropriate treatments can be selected based on different tumor stages. However, the condition of patients with HCC in China is complicated, and no single specialty offers the complete spectrum of care. The disease-centered multidisciplinary team for HCC is a crucial method to prolong the survival of patients with HCC and optimize their quality of life. Recent advancements in different disciplines have brought new opportunities in HCC treatments and altered multidisciplinary management approaches. Meanwhile, new challenges have emerged, and many problems have yet to be addressed.

Novel Strategies to Transform Breast Cancer From “Cold Tumor” to “Hot Tumor”
Abstract:

Immunotherapy represents the third revolution in the pharmacological treatment of tumors and has demonstrated considerable efficacy in the management of malignant solid tumors, including melanoma and lung cancer. By contrast, breast cancer is frequently categorized as a “cold tumor” because of its limited immunogenicity and immunoreactivity, which hinder research progress and clinical outcomes in immunotherapy. Only a small proportion of patients derive benefits from immunotherapeutic interventions, and the development of drug resistance remains a concern. In this regard, novel strategies should be explored for converting immunologically inert “cold tumors” into immunologically active “hot tumors”, thereby expanding the population that will benefit from breast cancer immunotherapy. This study reviews new strategies to transform breast cancer from “cold tumor” to “hot tumor”. Strategies include enhancing the expression of tumor antigens, promoting immune infiltration, and reversing the immunosuppressive microenvironment. Results also emphasize the importance of comprehensive treatment to enhance systemic immunity.

Research Progress on Regulation of Tumor Immune Microenvironment via Reactivation of Unbalanced Mitochondria in Traditional Chinese Medicine
Abstract:

The health of the human body is the result of the dynamic interplay between immunity and various microorganisms. Furthermore, the health of the mitochondrial grid determines the strength of immunity. Mitochondrial imbalance leads to the metabolic remodeling of intracellular nutrients, which accelerates the occurrence and development of tumors. The theory of yin and yang and the theory of visceral outward manifestation are the foundation and core of traditional Chinese medicine (TCM) theory, which guides the clinical diagnosis and treatment of TCM. Yang Qi is the driving force behind the metabolism and physiological functions of the human body; it is also the adenine nucleoside triphosphate produced efficiently by mitochondrial aerobic respiration. The main transport of spleen refers to the biological oxidation process of food in the mitochondria, and its normal function is closely related to the integrity of the mitochondrial structure and function of the cell. Therefore, warming yang and strengthening the spleen essentially means restoring the high production capacity of the mitochondria. Rebuilding damaged mitochondrial function, improving efficiency, and boosting the energy level of the neuro-endocrine-immune network are the key factors contributing to the body’s ability to resist disease and return to health.

Research Progress and Exploration on Standardized Surgical Procedures for Colorectal Cancer
Abstract:

The advancement of medical technology has led to significant progress in the research of standardized surgical procedures for colorectal cancer, resulting in enhanced treatment regimens from preoperative to postoperative stages. Standardized surgical procedures are crucial for improving patient survival rates, reducing recurrence rates, minimizing complications, and improving quality of life. This article summarizes the latest research results on the classification, surgical methods, and adjuvant therapy of colorectal cancer surgery; analyzes and explores standardized surgical treatment strategies; and aims to provide reference and guidance for the clinical management of colorectal cancer.

Summary of 16-Year Observation of Reflux Esophagitis-Like Symptoms in A Natural Village in A High-Incidence Area of Esophageal Cancer
Abstract:
Objective 

To investigate the screening results and factors affecting abnormal detection rates among high-risk groups of esophageal cancer and to explore effective intervention measures.

Methods 

We investigated and collected the information on gender, education level, age, marital status, symptoms of reflux esophagitis (heartburn, acid reflux, belching, hiccup, foreign body sensation in the pharynx, and difficulty swallowing), consumption of pickled vegetables, salt use, and esophageal cancer incidence of villagers in a natural village in Wenfeng District, Anyang City, Henan Province. Changes in reflux esophagitis symptoms in the high-incidence area of esophageal cancer before and after 16 years were observed, and the relationship of such changes with esophageal cancer was analyzed.

Results 

In 2008, 711 cases were epidemiologically investigated, including 213 cases with one of the symptoms of reflux esophagitis such as heartburn, acid reflux, belching, hiccups, foreign body sensation in the pharynx, and difficulty swallowing (sorted in accordance with the abovementioned symptoms; if there are multiple symptoms, then the former is taken); 55 cases with at least two related symptoms, among which the most symptom was heartburn in 108 cases (15.1%); followed by acid reflux, belching, etc. In 2024, the same group of people was investigated, and eight people were missing because of relocation. A total of 703 people were successfully investigated, of which 189 cases (26.8%) had one of the symptoms of reflux esophagitis, such as heartburn (sorted in accordance with relevant symptoms, if there are multiple symptoms, then the former will be selected); 167 cases (23.7%) had at least two related symptoms, among which the most symptom was heartburn in 139 cases (19.7%); followed by acid reflux. Over 16 years, among the 703 people investigated, 45 cases had esophageal cancer and they had one or more of the abovementioned symptoms. No significant differences in the reflux esophagitis-like symptoms were found between 2008 and 2024 (P=0.26); no significant differences in the composition of reflux esophagitis-like symptoms were found between 2008 and 2024 (P=0.299).

Conclusion 

The detection rate of reflux esophagitis-related symptoms in the population in a high-risk area of esophageal cancer has not decreased in the past 16 years, and the high-risk factors still exist. Esophageal cancer is closely related to reflux esophagitis, and clinical practice can provide early diagnosis and treatment for high-risk population.

BASIC RESEARCH
Modified Maimendong Decoction Inhibits Lung Cancer Metastasis by Up-Regulating Levels of NK and CD8+ T Cells in Peripheral Blood and Tumor Microenvironment
Abstract:
Objective 

To explore the mechanism of modified maimendong decoction (MMD) in inhibiting lung cancer metastasis from the perspective of immune regulation.

Methods 

CTC-TJH-01 and LLC cells were intervened with different concentrations of modified maimendong decoction. The cell proliferation was detected with a CCK-8 kit, apoptosis was detected with an Annexin V-FITC/PI kit, and cell migration was detected through Transwell assays. A lung metastasis model was established through the tail vein injection of LLC cells into C57BL/6 mice, and body weight change and lung tumor metastasis in the mice were evaluated after continuous gavage intervention with MMD. HE staining, immunohistochemistry, and immunofluorescence were employed to observe the histomorphology, Ki-67 protein level, and NK and T cell levels of metastatic lesions. The levels of NK and T cells in the peripheral blood of mice were detected throughflow cytometry.

Results 

MMD had no significant inhibitory effect on the proliferation, apoptosis, and migration of CTC-TJH-01 and LLC cells in vitro. In mice, MMD could significantly inhibit the lung metastasis of LLC cells, increase the proportion of NK and CD8+ T cells in peripheral blood and tumor microenvironment (P<0.05), and reduce the expression of Ki-67 protein in metastatic tumor tissues (P<0.05).

Conclusion 

MMD may inhibit the growth of metastatic tumors by upregulating the expression levels of NK and CD8+ T cells in peripheral blood to promote the elimination of circulating tumor cells, and regulating the infiltration of NK and CD8+ T cells in the immune microenvironment of metastatic tumors, then play an antimetastatic role in lung cancer.

BASIC RESEARCH
Cyclin F Expression in Clear Cell Renal Cell Carcinoma and Its Effect on Biological Behavior of Renal Carcinoma Cell Lines
Abstract:
Objective 

To investigate the expression of Cyclin F in clear cell renal cell carcinoma (ccRCC), its clinicopathological characteristics, and its effect on the biological behavior of renal cancer cell lines

Methods 

RT-qPCR and Western blot were used to detect the mRNA and protein expression of Cyclin F in fresh ccRCC specimens. Immunohistochemistry assay was performed to detect the expression of Cyclin F protein in 80 paraffin samples. CCK-8 assay, scratch assay, and flow cytometry were conducted to determine the effects of Cyclin F overexpression on the proliferation, migration, and apoptosis of renal cancer cell lines.

Results 

The expression of Cyclin F in cancer tissues was higher than that in adjacent tissues at the mRNA level (P<0.0285). The expression of Cyclin Fprotein in cancer tissues was lower than that in adjacent tissues (P<0.001). The analysis of clinicopathological parameters showed that the low expression of Cyclin F was correlated with WHO/ISUP grade, Ki67 index, and age (P=0.041, 0.047, 0.008,). In vitro experiments confirmed that overexpression of Cyclin F promoted the proliferation (P<0.001) and migratory ability (24 h P=0.003, 48 h P=0.0058) of the RCC 786-O cell line, while inhibiting apoptosis (P=0.0019).

Conclusion 

The low expression of Cyclin F protein in ccRCC tissuesis associated with high ISUP grade, high Ki67 index, oldage, and prognosis of patients.

Clinical Importance of BAIAP2L1 Expression in Cervical Cancer and Its Effect on Malignant Phenotype of Cervical Cancer Cells
Abstract:
Objective 

To explore the expression characteristics of BAIAP2L1 in cervical cancer (CC) and its regulatory role in tumor cell metastasis.

Methods 

The correlation between BAIAP2L1 expression and clinical prognosis was analyzed by using a public database. GO pathway enrichment and clinicopathological correlation analyses were conducted by employing R language. The effect of BAIAP2L1 knockdown on CC cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) were further investigated through gene silencing approaches.

Results 

BAIAP2L1 expression was significantly upregulated in CC tissues (Padj <0.001) and it was identified as an independent risk factor for patient mortality (HR=2.808, P=0.03). Elevated BAIAP2L1 levels showed significant correlations with poor overall survival, advanced T/N stage, recurrence, and metastasis (all P<0.05). Functional enrichment analysis revealed its involvement in tumor metastasis-related pathways. The knockdown of BAIAP2L1 significantly attenuated CC cell proliferation, invasion, and migration and suppressed key EMT processes (all P<0.05).

Conclusion 

BAIAP2L1 is overexpressed in CC tissues and associated with patient prognosis and metastasis. The targeted inhibition of BAIAP2L1 can effectively curb tumor progression.

CLINICAL RESEARCH
Clinicopathological Characteristics of HER2-Positive Breast Cancer Patients with BRCA1/2 Pathogenic Variants and Their Response to Neoadjuvant Targeted Therapy
Abstract:
Objective 

To analyze the proportion and clinicopathological characteristics of HER2-positive breast cancer patients with BRCA1/2 pathogenic variants, and their response to neoadjuvant anti-HER2 targeted therapy.

Methods 

The clinicopathological data of 531 breast cancer patients with germline BRCA1/2 pathogenic variants (201 with BRCA1 variants and 330 with BRCA2 variants) were analyzed.

Results 

Among the 201 BRCA1 and 330 BRCA2 variants, 17 (8.5%) and 42 (12.7%) HER2-positive breast cancer cases were identified, respectively, accounting for 11.1% of all BRCA1/2-mutated breast cancers. Compared with BRCA1/2-mutated HR-positive/HER2-negative patients, HER2-positive patients did not present any significant differences in clinicopathological features; however, compared with triple-negative breast cancer patients, HER2-positive patients had a later onset age and lower tumor grade. Among the 17 patients who received neoadjuvant anti-HER2 targeted therapy, 10 cases achieved pCR (58.8%), whereas 7 cases did not (41.2%).

Conclusion 

HER2-positive breast cancer accounts for more than 10% of BRCA1/2-mutated patients. Approximately 40% of these patients fail to achieve pCR after neoadjuvant targeted therapy. This phenomenon highlights the possibility of combining anti-HER2 targeted agents with poly (adenosine diphosphate-ribose) polymerase inhibitors.

Causal Relationship Between Colorectal Cancer and Common Psychiatric Disorders: A Two-sample Mendelian Randomization Study
Abstract:
Objective 

To elucidate the causal relationships between colorectal cancer (CRC) and prevalent psychiatric disorders through a two-sample Mendelian randomization approach.

Methods 

Utilizing publicly available genome-wide association study data, we explored the connections between CRC and various psychiatric disorders, including depression, anxiety, bipolar disorder, and schizophrenia. We applied three statistical analyses: inverse variance weighting, MR-Egger, and median weighting. Sensitivity analyses were conducted to ensure the reliability and validity of the results.

Results 

Inverse variance weighting analysis showed no significant links between CRC and depression (P=0.090), anxiety (P=0.099), or schizophrenia (P=0.899). Conversely, a significant inverse relationship was found with bipolar disorder (P=0.010).

Conclusion 

No causal connection exists between CRC and the psychiatric conditions of depression, anxiety, or schizophrenia. However, CRC may have a causal association with a reduced risk of bipolar disorder, further supporting the existence of the gut-brain axis.

Expression and Clinical Significance of PLCβ4 Gene in Hepatocellular Carcinoma Analyzed Based on TCGA Database and Experimental Validation
Abstract:
Objective 

To analyze the PLCβ4 gene mRNA expression and its clinical significance in hepatocellular carcinoma (HCC) based on TCGA database.

Methods 

Based on the data on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of nontumor liver tissues) in the TCGA database, Kaplan–Meier method, Cox regression analysis, and immune infiltration analysis were performed to evaluate the relationship between PLCβ4 gene and the clinical characteristics and survival prognosis of HCC patients. Correlation analysis between PLCβ4 gene and 24 types of immune cells was applied to investigate the relationship between PLCβ4 gene and immune cell infiltration and mRNA expression level of TP53 gene, a high-frequency mutation gene in HCC. In addition, paraffin sections of highly, moderately, and poorly differentiated tumor tissues and normal liver tissues from HCC patients were collected. The histopathological observation was carried out via HE staining method, and the expression levels of PLCβ4 and Ki-67 proteins in each clinical sample were verified through the immunohistochemical method.

Results 

The expression level of PLCβ4 gene in HCC was significantly higher than that in normal tissues (P<0.01), and all patients in the PLCβ4 high-expression group had a significantly longer overall survival than those in the low-expression group (P<0.05), which suggested that PLCβ4 substantially affected the prognosis of HCC patients. Correlation analysis showed that the expression level of PLCβ4 gene was highly correlated with immune cell infiltration and the expression level of TP53 gene. As verified by clinical sample experiments, HE staining experiments and immunohistochemical results revealed that PLCβ4 gene expression in HCC tissue samples was significantly higher than that in normal tissues (P<0.001), and it was negatively correlated with the degree of differentiation.

Conclusion 

PLCβ4 may serve as an independent prognostic factor in HCC and is expected to be a novel molecular target for HCC treatment.

CLINICAL RESEARCH
Mendelian Randomization Analysis of Correlation Between Interleukin and Risk of Gynecological Tumors
Abstract:
Objective 

To investigate the relationship between different interleukins (ILs) and gynecological tumors, including cervical cancer, endometrial cancer, and uterine leiomyoma using two-sample Mendelian randomization (MR) analysis.

Methods 

IL and gynecological tumor data were obtained from European populations by using the IEU OpenGWAS open database. Two-sample MR analysis was applied, different interleukins were used as exposure factors, significant SNP in GWAS data were selected as instrumental variables, and the instrumental variables were independent of each other. The risk of three kinds of gynecological tumors was analyzed separately to explore the causal relationship between ILs predicted by genes and outcome indicators. The TwoSampleMR package in R language (4.3.1) software was used for statistical analysis. MR analysis was performed using inverse variance weighted, MR Egger regression, weighted median, simple mode, and weighted mode methods.

Results 

IL-18 receptor 1 (P=0.039) and IL-24 (P=0.025) were negatively correlated with the risk of cervical cancer. IL-4 (P=0.040), IL-21 (P=0.026), and IL-37 (P=0.027) were positively correlated with the risk of endometrial cancer. IL-15 receptor subunit alpha (P=0.005) was negatively correlated with the risk of endometrial cancer. IL-17A (P=0.005) and IL-37 (P=0.018) were negatively correlated with the risk of uterine leiomyoma. IL-21 (P=0.035) was positively correlated with the risk of uterine leiomyoma.

Conclusion 

Genetically predicted IL-4, IL-15Rα, IL-17A, IL-18R1, IL-21, IL-24, and IL-37 are causally associated with the risk of three gynecological tumors. Further exploration of the molecular mechanism of ILs in gynecological tumors may provide potential therapeutic targets for the treatment of gynecological tumors.

GUIDELINES INTERPRETATION
Interpretation of Key Points in 2024 Chinese Expert Consensus on EGFR Exon 20 Insertion Mutations in Non-Small Cell Lung Cancer
Abstract:

The Chinese Society of Clinical Oncology (CSCO) NSCLC Expert Committee has updated the 2023 Chinese expert consensus in light of the growing understanding of epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations in non-small cell lung cancer (NSCLC) and the emergence of new clinical data from targeted therapies. Based on the latest domestic and international literature, clinical evidence, and expert experience, the “Chinese Expert Consensus on the Standardized Diagnosis and Treatment of Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations (2024 Edition)” introduces refinements in the diagnostic and upcoming therapeutic strategies for this rare mutation. This article also highlights the key updates and recommendations in the 2024 consensus compared to the 2023 version as well as outlines future directions to optimize clinical practices and improve patient outcomes.

REVIEWS
Research Progress of Immune Checkpoint Inhibitors Combined with Anti-Angiogenic Drugs in Treatment of Advanced Non-Small Cell Lung Cancer
Abstract:

The use of immune checkpoint inhibitors (ICIs) improves the prognosis of patients with advanced non-small cell lung cancer (NSCLC). However, some patients still fail to benefit from them. In recent years, studies have demonstrated that the combination of antiangiogenic agents with ICIs can enhance the antitumor effect, and guidelines at home and abroad have suggested that the combination of ICIs with antiangiogenic regimens can be used in patients with advanced NSCLC. Therefore, the mechanism of action and the latest clinical studies on the combination of ICIs and anti-angiogenic drugs in the treatment of advanced NSCLC were reviewed in this article to provide reference for treating advanced NSCLC.