Objective To investigate the expression and clinical significance of S100A4 protein in tumorstroma of nonsmall cell lung cancer（NSCLC） to study its correlation with invasion, metastasis and prognosis. Methods Immunohistochemical staining（SP method）for S100A4 protein expression was performed in tissue sections from 130 patients with NSCLC operated and to analyze association of S100A4 protein with clinicopathological parameters in lung cancer and prognosis. Results The total positive expression rates of S100A4 protein in stroma of NSCLC was 72.3%. The positive expression rates of S100A4 protein in stroma of squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma and large cell lung cancer were 84.3%，59.6%，70.0% and 75% respectively.The expression of S100A4 protein was significantly associated with lymph node metastasis (χ2=18.91, P=0.000), distant metastasis(χ2=5.51, P=0.019) and TNM stage (χ2=21.54, P=0.000). The 3 years survival rates of patients whose tumourstroma stained positive for S100A4 was lower than that of patients whose tumourstroma stained negative (36.2% vs. 63.9%, P=0.003). Cox’ risk ratio model analysis indicated that age ≤50 years (OR=1.866), lymph node metastasis(OR=1.826), distant metastasis(OR=6.224), lower histology differentiation and undifferentiation (OR=1.793), TNM stage Ⅲ-Ⅳ (OR=2.573) and positive expression of S100A4 protein in stroma of NSCLC(OR=1.776) were significantly independent prognostic factors which affected survival. Conclusion Expression of S100A4 protein in stroma of NSCLC is significantly associated with invasion, metastasis, TNM stage and prognosis. S100A4 protein might become a marker for prediction of tumor progression of disease and clinical therapy.
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.
In recent years, the computer science represented by artificial intelligence and high-throughput sequencing technology represented by omics play a significant role in the medical field. This paper reviews the research progress of the application of artificial intelligence combined with omics data analysis in the diagnosis and treatment of non-small cell lung cancer (NSCLC), aiming to provide ideas for the development of a more effective artificial intelligence algorithm, and improve the diagnosis rate and prognosis of patients with early NSCLC through a non-invasive way.
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.
Abstract： Objective To evaluate the safety, feasibility, and clinical outcome of complete video-assisted thoracoscopic surgery （VATS） lobectomy for patients with early-stage non-small cell lung cancer （NSCLC）. Methods We retrospectively analyzed the clinical data of 160 consecutive patients（the VATS group, 83 males and 77 females with average age at 60.8 years）with early-stage NSCLC who underwent complete VATS lobectomy between January 2005 andDecember 2008 in Zhongshan Hospital of Fudan University，and compared them with 357 patients（the thoracotomy group, 222 males and 135 females with average age at 59.5 years）who underwent open thoracotomy in the same period. Results The conversion rate of the VATS group was 5.0%（8/160）. The operation time of the VATS group was significantly shorter than that of the thoracotomy group（113.0 min vs.125.0 min, P=0.039）. Length of postoperative hospital stay was not statistically different between the two groups（10.3±4.3 d vs.9.1±4.6 d，P=0.425）. The postoperative morbidity of the VATS lobectomy group and the thoracotomy group was 9.4%（15/160）and 10.1% （36/357） respectively，and the postoperative mortality of the two groups was 0.6%（1/160）and 2.0%（7/357）respectively. There was no statistical difference in the mean group of lymph node dissection （2.4±1.5 groups vs.2.4±1.7 groups，P=0.743） and the mean number of lymph node dissection （9.8±6.3 vs.10.1±6.4，P=0.626） between the two groups. The overall 5-year survival rate of the VATS group was significantly higher than that of the thoracotomy group （81.5% vs.67.8%, P=0.001）. Subgroup analysis showed that the 5-year survival rate of pⅠa stage, pⅠb stage, and pⅢa stage was 86.0%, 84.5%, and 58.8% respectively in the VATS group, and 92.9%, 76.4%, and 25.3% respectively in the thoracotomy group. Conclusion Complete VATS lobectomy is technically safe and feasible for patients with early-stage NSCLC. The lymph node dissection extension of complete VATS lobectomy is similar to that of open thoracotomy, and long-term outcome of complete VATS lobectomy is superior to that of open thoracotomy. Randomized controlled trials of large sample size are further needed to demonstrate superiority.
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.
目的 探讨非小细胞肺癌合并孤立性脑转移灶的手术治疗效果，分析影响患者生存期的因素。 方法 回顾性分析2005年1月－2011年5月46例接受手术治疗的非小细胞肺癌合并孤立性脑转移灶患者的临床资料，其中男35例，女11例；年龄35～67岁，平均53.2岁；所有患者均行肺部原发肿瘤及脑部转移肿瘤切除术，其中肺叶切除术42例，全肺切除术4例，术后全部患者行全脑放射治疗，部分患者行系统化学疗法3～6周期。对随访患者的生存时间采用对数秩检验，分析影响生存率的因素。 结果 术后病理检查提示腺癌27例，鳞癌15例，大细胞癌2例，其他类型2例。患者1年生存率80%，2年生存率41%，3年生存率14%，中位生存期23个月，平均生存期（27.8 ± 4.5）个月（乘积极限法）。对数秩检验结果提示N0与N1患者比N2患者生存率高（P=0.024），腺癌患者生存期比非腺癌患者生存期长（P=0.002）。 结论 外科手术治疗非小细胞肺癌合并孤立性脑转移灶的患者可以取得良好的治疗效果，腺癌患者及无纵隔淋巴结转移的患者生存期长。