Lung cancer is one of the most malignant common tumor worldwidely and it's the most popular cancer in China. Both the prevalence and mortality of it are higher than other cancers. And its 5-year survival rate is 15%. Non-small cell lung cancer(NSCLC) accounts for about 85% lung cancer and its pathogenesis has not been elucidated. Therefore, early prediction and detection are very important for improving the effect of treatment and prognosis. Recently, dysregulation and excessive activity of the C4.4A as a member of the LY6/uPAR family of membrane proteins has been shown to associate with multiple cancer types. And previous studies suggest that the C4.4A participates in the invasion and metastasis of NSCLC. At the same time, circumstantial evidence proves that C4.4A and liver kinase B1(LKB1) tumor suppressor gene have a negative regulatory relationship. This article will briefly summarize the recent research progresses of C4.4A in NSCLC.
Objective To investigate the prognostic value of ERBB2 Exon20ins (Exon20ins) in advanced non-small cell lung cancer (NSCLC) patients receiving first-line chemotherapy combined with immunotherapy. Methods A retrospective analysis was conducted on clinical data from ERBB2-mutant stage IV NSCLC patients who received first-line chemotherapy combined with immunotherapy at West China Hospital of Sichuan University between 2020 and 2024. ERBB2 wild-type patients were matched using propensity score matching. Clinical pathological characteristics, distant metastatic sites, and treatment outcomes were compared among patients with different mutation statuses. The primary endpoint was progression-free survival (PFS), and Kaplan-Meier method was used to plot survival curves. Cox regression analysis was performed to adjust for confounding factors. Results This study included 41 ERBB2-mutant stage IV NSCLC patients, of whom 22 had Exon20ins mutations, and 19 had other ERBB2 mutations. Forty-one ERBB2 wild-type patients were matched for comparison. The mean age of all patients was 60.0±9.3 years, with 61 males (74.4%). A total of 67 patients (81.7%) received chemotherapy combined with immunotherapy, and 15 patients (18.3%) received chemotherapy combined with immunotherapy and anti-angiogenesis therapy. The Exon20ins group showed a higher incidence of lymph node metastasis compared with the ERBB2 other mutation group and the wild-type group (36.4% vs. 15.8% vs. 9.8%, P=0.045). The median PFS in the Exon20ins group was significantly shorter than in the other mutation group (5.8 months vs. 10.3 months, P=0.025) and the wild-type group (5.8 months vs. 8.3 months, P=0.023). Univariate Cox regression analysis indicated that the ERBB2 Exon20ins mutation was an adverse prognostic factor (Exon20ins vs. other ERBB2 mutations, HR=2.9, 95%CI 1.18 - 7.1, P=0.014; Exon20ins vs. wild-type, HR=2.6, 95%CI 1.25 - 5.6, P=0.014). The combination with anti-angiogenesis therapy did not significantly affect the prognosis of PFS (HR=0.66, 95%CI 0.28 - 1.6, P=0.363). Multivariate Cox regression analysis revealed that the ERBB2 Exon20ins mutation was an independent adverse prognostic factor for PFS (Exon20ins vs. other ERBB2 mutations, HR=3.3, 95%CI 1.27 - 8.3, P=0.015; Exon20ins vs. wild-type, HR=2.7, 95%CI 1.2 - 5.88, P=0.014). For the 67 patients receiving chemotherapy combined with immunotherapy, Cox regression analysis showed that the ERBB2 Exon20ins mutation was still associated with poor prognosis in advanced NSCLC (Exon20ins vs. other ERBB2 mutations, HR=3.2, 95%CI 1.12 - 9.1, P=0.030; Exon20ins vs. wild-type, HR=2.5, 95%CI 1 - 5.88, P=0.040). Conclusions Advanced NSCLC patients with ERBB2 Exon20ins mutation have a worse prognosis compared with those with other ERBB2 mutation subtypes or ERBB2 wild-type when treated with first-line chemotherapy combined with immunotherapy. This suggests that ERBB2 Exon20ins mutation, as a particularly refractory mutation, requires the exploration of new combination strategies based on molecular subtyping to improve survival outcomes.
Non-small cell lung cancer (NSCLC) is one of the most common types of cancer in the world and is an important cause for cancer death. Although the application of immunotherapy in recent years has greatly improved the prognosis of NSCLC, there are still huge challenges in the treatment of NSCLC. The immune microenvironment plays an important role in the process of NSCLC development, infiltration and metastasis, and they can interact and influence each other, forming a vicious circle. Notably, single-cell RNA sequencing enables high-resolution analysis of individual cells and is of great value in revealing cell types, cell evolution trajectories, molecular mechanisms of cell differentiation, and intercellular regulation within the immune microenvironment. Single-cell RNA sequencing is expected to uncover more promising immunotherapies. This article reviews the important researches and latest achievements of single-cell RNA sequencing in the immune microenvironment of NSCLC, and aims to explore the significance of applying single-cell RNA sequencing to analyze the immune microenvironment of NSCLC.
Objective To predict clinical chemotherapy sensitivity of primary non-small cell lung cancer（NSCLC） by methylthiazal （MTT） tumor chemosensitivity assay method in vitro and detection of multidrug resistance gene1 （MDR1）, and provide reference for clinical individualized treatment. Methods We selected 80 fresh primary NSCLC samples from NSCLC patients who underwent surgical resection in Zibo Central Hospital Affiliated to Binzhou Medical College between January 2009 and December 2011. There were 46 male patients and 34 female patients with their median age of 54 （29 to 81）years. Viable NSCLC cells obtained from malignant tissue were tested for their sensitivity to cisplatin （DDP）, gemcitabine （GEM）, docetaxe （DOC）, etoposide （VP-16） ,and vinorelbine （NVB） using MTT assay in vitro. Fluorescent quantitative reverse transcriptase-polymerase chain reaction （RT-PCR） was used to analysis the expression level of multidrug resistance gene1 （MDR1）. Results After exposure to antitumor drugs, morphologic changes, decrease of metabolic activity, and apoptosis were detected in NSCLC cells. MTT results showed that different individual cancer cells had different chemosensitivity to antitumor drugs, and cancer cells also had different chemosensitivity to different antitumor drugs. Inhibitory rates of cancer cells exposed to DOC, GEM, and VP-16 were significantly higher than those of cancer cells exposed to DDP and NVB （42.5%±9.5%, 40.5%±6.5%, 38.4%±7.6% versus 31.5%±8.5%，32.5%±7.8%, P＜0.05）.The positive rate of MDR1 in tumor tissues was 40.0% （32/80）. The expression of MDR1 was not associated with tumor histological type, degree of differentiation, lymph node metastasis and TNM stage. The expression of MDR1 was associated with resistance to NVB （χ2=5.209，P=0.022），GEM （χ2=4.769，P=0.029），VP-16 （χ2=4.596，P=0.032），and DDP（χ2=6.086，P=0.014）, but not associated with resistance to DOC（χ2=0.430，P=0.512）. Conclusion MTT chemosensitivity assay can effectively predict clinical chemotherapy sensitivity. Detection of MDR1, together with MTT chemosensitivity assay, can more accurately predict NSCLC chemosensitivity and be a guide for individualized chemotherapy of NSCLC.
This study reports a case of a 56-year-old female patient with BRAF-mutated non-small cell lung cancer (NSCLC) who successfully underwent curative surgery after neoadjuvant targeted therapy with the BRAF inhibitor dabrafenib combined with the MEK inhibitor trametinib. The chest drainage tube was removed 2 days postoperatively, and the patient was discharged smoothly. Postoperative pathology indicated invasive adenocarcinoma, moderately to highly differentiated, with 80% being lepidic type, and the maximum tumor diameter was 4 cm. No vascular invasion, nerve invasion, air cavity dissemination, pleural invasion, or lymph node metastasis were observed. The postoperative staging was ypT2aN0M0. The patient continued with adjuvant treatment with dabrafenib combined with trametinib postoperatively, and no signs of recurrence were found in the follow-up examination six months after surgery.
Objective To compare the perioperative results between uniportal and three-portal thoracoscopic lobectomy for non-small cell lung cancer (NSCLC). Methods Electronic databases including PubMed, Web of Science, EMbase, CNKI, Wanfang were systematically searched from the establishment of each database until April 2022. Literature screening, data extraction and bias risk assessment were independently conducted by two researchers. All combined results were performed by RevMan 5.3 and Stata 16.0. The quality of the literature and the risk of bias were evaluated using the Cochrane Bias Risk Assessment Tool. Results Eighteen eligible randomized controlled trials (1 597 patients) were identified eventually, including 800 patients undergoing uniportal thoracoscopic lobectomy and 797 patients undergoing three-portal thoracoscopic lobectomy. Meta-analysis results showed that compared to the three-portal approach, uniportal lobectomy took longer operation time (WMD=7.63, 95%CI 2.36 to 12.91, P=0.005) with less intraoperative blood loss (WMD=–28.81, 95%CI –42.54 to –15.08, P<0.001). Furthermore, patients undergoing uniportal lobectomy achieved lower visual analogue score within 24 hours after the operation (WMD=–1.60, 95%CI –2.26 to –0.94, P<0.001), less volume of drainage after the operation (WMD=–25.30, 95%CI –46.22 to –4.37, P=0.020), as well as shorter drainage duration (WMD=–0.36, 95%CI –0.72 to –0.01, P=0.040). Besides, patients undergoing uniportal lobectomy were also observed with shorter length of hospital stay (WMD=–2.28, 95%CI –2.68 to –1.88, P<0.001) and lower incidence of postoperative complications (RR=0.49, 95%CI 0.38 to 0.63, P<0.001). However, the number of lymph nodes harvested during the operation (WMD=–0.01, 95%CI –0.24 to 0.21, P=0.930) was similar between the two groups. Conclusion Both uniportal and three-portal thoracoscopic lobectomy for NSCLC are safe and feasible. The uniportal approach is superior in reducing short-term postoperative pain, postoperative complications and shortening the length of hospital stay.
ObjectiveTo detect mRNA and protein expression of CUG-binding protein 1(CUGBP1)in non-small cell lung cancer (NSCLC), and assess the prognostic significance of CUGBP1.
MethodsFifty-seven NSCLC patients who received surgical resection at the Department of Thoracic Surgery of Affiliated Hospital of Qingdao University between July 2009 and April 2011 were enrolled in this study. There were 32 male and 25 female patients with their age of 43-74 (60.6±8.9) years. The expressions of CUGBP1 mRNA and protein in tumor and adjacent normal tissues were detected by semi-quantitative RT-PCR and immunohistochemistry. All the patients were followed up every 2 months after discharge via the phone. Time to progression(TTP) was used to evaluate the relationship between CUGBP1 mRNA, clinicopathological variables and prognosis. The percentage of CUGBP1 mRNA and CUGBP1 expression was correlated with clinical characteristics using χ2 test. The prognostic significance of CUGBP1 mRNA was assessed by univariate and multivariate analysis using Cox regression analysis.
ResultsThe expressions of CUGBP1 mRNA and CUGBP1 were over-expressed in cancer tissue, and were significantly correlated with TNM-stage and differentiation. Univariate and multivariate analysis showed that CUGBP1 mRNA expression(P=0.0074, HR=3.701, 95% CI 1.420-9.648), TNM-stage (P < 0.000 1, HR=4.043, 95% CI 2.098-7.794) and age (P=0.0018, HR=3.207, 95% CI 1.544-6.664) were independent predictors of postsurgical survival in NSCLC patients.
ConclusionsCUGBP1 mRNA and CUGBP1 are over-expressed in NSCLC, and over-expression of CUGBP1 mRNA independently predicts a shorter postsurgical survival in NSCLC patients.
Objective To evaluate the clinical effectiveness and safety of radiotherapy (RT) combined with hyperthermia (HT) for locally-advanced non-small cell lung cancer (NSCLC). Methods The randomized controlled trials (RCTs) on RT plus HT vs. RT alone for locally-advanced NSCLC were searched in PubMed, The Cochrane Library, EMbase, VIP, CNKI, CBM and other electronic databases from inception to November 2011. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data and assessed quality of the included studies independently. Then meta-analyses were performed using RevMan 5.0.2. Results A total of 9 RCTs involving 527 cases were included. The results of meta-analyses showed that compared with the RT alone group, the RT plus HT group could increase the total effective rate (OR=2.08, 95%CI 1.44 to 3.02, P=0.000 1) and the progression-free survival rate (OR=4.85, 95%CI 1.88 to 12.48, P=0.001). However, there were no significant differences between the two groups in the overall survival rate (OR=1.13, 95%CI 0.64 to 1.98, P=0.68), symptoms improve rate (OR=3.37, 95%CI 1.68 to 6.78, P=0.000 6), and other acute adverse reactions. Conclusion Current results of systematic review show that radiotherapy combined with hyperthermia can obviously increase the total effective rate and improve the progression-free survival rate for locally-advanced NSCLC, and doesn’t increase the incidence of adverse reaction. Therefore, radiotherapy combined with hyperthermia is a fairly reasonable and effective treatment method for locally-advanced NSCLC.
With the publication of several phase Ⅱ and Ⅲ clinical studies, the multidisciplinary diagnostic and therapeutic strategies for early resectable non-small cell lung cancer (rNSCLC) are rapidly evolving. These studies have elucidated the significant effects of neoadjuvant and adjuvant therapies on improving the prognosis of rNSCLC patients, while also highlighting the urgent need to revise and refine corresponding treatment protocols and clinical pathways. In response, the International Association for the Study of Lung Cancer has assembled a diverse, multidisciplinary international expert panel to evaluate current clinical trials related to rNSCLC and to provide diagnostic, staging, and treatment recommendations for rNSCLC patients in accordance with the 8th edition of the AJCC-UICC staging system. The consensus recommendations titled "Neoadjuvant and adjuvant treatments for early stage resectable non-small cell lung cancer: Consensus recommendations from the International Associationfor the Study of Lung Cancer" outline 20 recommendations, 19 of which received over 85% agreement from the experts. The recommendations indicate that early rNSCLC patients should undergo evaluation by a multidisciplinary team and complete necessary imaging studies. For stage Ⅱ patients, consideration should be given to either adjuvant therapy following surgery or direct neoadjuvant/perioperative treatment, while stage Ⅲ patients are recommended to receive neoadjuvant chemoimmunotherapy followed by surgery. Postoperatively, adjuvant immunotherapy should be considered based on the expression levels of programmed cell death ligand 1, along with testing for other oncogenic driver mutations. For patients with epidermal growth factor receptor or anaplastic lymphoma kinase mutations sensitive to tyrosine kinase inhibitors, corresponding adjuvant targeted therapy is recommended. These recommendations aim to provide personalized and precise treatment strategies for early rNSCLC patients to enhance the efficacy of neoadjuvant and adjuvant therapies. This article provides an in-depth interpretation of these consensus recommendations.
ObjectiveTo explore the relationship of the clinicopathological characteristics of non-small cell lung cancer (NSCLC) with the mutations of epidermal growth factor receptor (EGFR), K-ras and EML4-ALK fusion gene in cell blocks of pleural effusion (PLE).
MethodsA total of 268 cytological specimens of PLE (pleural effusion), from Central Hospital of Zibo city were collected from advanced NSCLC patients between January 2012 year and June 2014 year. There were 165 male and 103 female patients at age of 53.6 (31-76) years. Qualitative diagnosis has been made in the 268 patients using PLE samples with conventional smear. Immunohistochemical staining combined with cell block section were used for further classification. There were 76 patients diagnosed as NSCLC with 39 patients of adenocarcinoma and 37 patients of squamous-cell carcinoma. In the 76 patients of lung biopsy specimens and PLE, EGFR and K-ras mutations, EML4-ALK fusions were tested.
ResultsEGFR mutations rate was 34.21% (26/76). K-ras mutations rate was 6.58% (5/76). EML4-ALK fusions rate was 7.89% (6/76) at the same time. EGFR and K-ras mutations, EML4-ALK fusions were mostly found in young female adenocarcinoma patients who were non-smokers. EGFR and K-ras mutations or EML4-ALK fusions were not found in the same patient.
ConclusionCytological specimens are feasible for detecting EGFR were K-ras mutations and EML4-ALK fusions. This will especially benefit to patients whose histological specimen can not be obtained.
