Establishment of patient-derived xenografts of retinoblastoma and choroidal melanoma on the avian chorioallantoic membrane

Purpose: To develop a viable in vivo chorioallantoic membrane (CAM) model to study the growth and invasion of patient?derived retinoblastoma (RB) and choroidal melanoma (CM) xenografts (PDXs). The study utilizes primary tumor samples instead of cancer cell lines, which provides a more authentic representation of tumors due to conserved morphology and heterogeneity. Methods: Fertilized chicken eggs were procured, windowed, and their CAM layers were dropped. On embryonic development day (EDD) 10, freshly cut patient?derived CM and RB tumors were implanted on the CAM layer and the setup was incubated for 7 days. The tumor?embedded CAM layer was harvested on EDD 17, and the extracted tumor samples were subjected to hematoxylin and eosin staining and immunohistochemical analysis to evaluate the extent of tumor invasion. Results: Significant changes in the vascularity around the RB and CM PDXs were observed, indicating an angiogenic environment. The cross?sectional histological view of the tumor implant site revealed the invasion of both the tumors into the CAM mesoderm. Invasion of CM into CAM mesoderm was visualized in the form of pigmented nodules, and that of RB was indicated by synaptophysin and Ki?67 positivity in Immunohistochemistry (IHC). Conclusion: The CAM xenograft model was successfully able to support the growth of CM and RB PDXs and their invasion in CAM, thus presenting as a feasible alternative to mammalian models for studying tumorigenicity and invasiveness of ocular tumors. Moreover, this model can further be utilized to develop personalized medicine by inoculating patient?specific tumors for preclinical drug screening.

Discovery of a first-in-class ANXA3 degrader for the treatment of triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a nasty disease with extremely high malignancy and poor prognosis. Annexin A3 (ANXA3) is a potential prognosis biomarker, displaying an excellent correlation of ANXA3 overexpression with patients' poor prognosis. Silencing the expression of ANXA3 effectively inhibits the proliferation and metastasis of TNBC, suggesting that ANXA3 can be a promising therapeutic target to treat TNBC. Herein, we report a first-in-class ANXA3-targeted small molecule (R)-SL18, which demonstrated excellent anti-proliferative and anti-invasive activities to TNBC cells. (R)-SL18 directly bound to ANXA3 and increased its ubiquitination, thereby inducing ANXA3 degradation with moderate family selectivity. Importantly, (R)-SL18 showed a safe and effective therapeutic potency in a high ANXA3-expressing TNBC patient-derived xenograft model. Furthermore, (R)-SL18 could reduce the β-catenin level, and accordingly inhibit the Wnt/β-catenin signaling pathway in TNBC cells. Collectively, our data suggested that targeting degradation of ANXA3 by (R)-SL18 possesses the potential to treat TNBC.

Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma / 医学前沿

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.

Development of the patient-derived xenograft model for gallbladder carcinoma and gene screening for tumor associated mutations / 中华肝胆外科杂志

Objective:To establish a patient-derived xenograft (PDX) model of gallbladder carcinoma (GBC) and to screen mutated genes associated with GBC with the aim to provide an effective preclinical model with novel therapeutic targets for individualized patient treatment.Methods:The PDX model of GBC was established by transplantation of fresh GBC tissues from 10 patients into subcutaneous tissues of nude mice. In two of these mice, the PDX tumor tissues were stained with HE, Ki67 immunohistochemical staining and whole exome sequencing (WES). The biological characteristics of the PDX tumor tissues were compared with those of the primary donor tumors in histological structure and molecular pathology, and a high-throughput screening of tumor mutation genes was then carried out.Results:In this study, the success rate of the PDX model of GBC was 70% (7/10). The pathological and growth characteristics of PDX tumor tissues and donor tumors were basically similar. In the 2 modeled cases sequenced by WES, the same rates between the harmful mutant genes in the PDX model and primary donor tumor were 71.4% (15/21) and 65.2% (15/23), and the same genes accounted for 93.8% (15/16) and 71.4% (15/21) in the harmful mutant gene of the PDX model. The 22 mutated genes, including TP53, ABCC4 and AMPD1, were involved both in the two donor tumors, and the model tumor tissues. Ten genes including TP53 and ABCC4 were screened out and they might be closely related to development of GBC by bioinformatics analysis.Conclusions:The PDX model of GBC could effectively be used in patients with GBC in this preclinical study on individualized patient treatment. In addition, 10 mutated genes, including TP53 and ABCC4 and the like, may be used as new potential therapeutic targets for GBC.

Comparison of B-NDG and BALB/c mouse models bearing patient-derived xenografts of esophageal squamous cell carcinoma / 南方医科大学学报

OBJECTIVE@#To investigate the difference of tumor formation in different mouse strains bearing patient-derived xenograft of esophageal squamous cell carcinoma(ESCC) and establish a better animal model for preclinical study of individualized treatment of ESCC.@*METHODS@#The tumor tissues collected from 22 ESCC patients were used to establish tumor-bearing mouse models in B-NDG (NSG) mice and BALB/c nude mice. The tumor formation rate and tumor formation time were compared between the two mouse models, and HE staining, immunohistochemistry and genome sequencing were carried out to assess the consistency between transplanted tumor tissues in the models and patient-derived tumor tissues.@*RESULTS@#The tumor-bearing models were established successfully in both NSG mice (50%, 11/22) and BALB/c nude mice (18.18%, 4/22). The average tumor formation time was significantly shorter in NSG mice than in BALB/c nude mice (75.95 91.67 days, < 0.001). In both of the mouse models, the transplanted tumors maintained morphological characteristics identical to those of patient-derived ESCC tumors. Genetic analysis showed that the xenografts in NSG mice had a greater genetic similarity to the patients' tumors than those in BALB/c nude mice ( < 0.0001).@*CONCLUSIONS@#Mouse models bearing xenografts of patient-derived ESCC can be successfully established in both NSG mice and BALB/c nude mice, but the models in the former mouse strain can be more reliable.

Establishment of a lung cancer mouse model with humanized immunity and its role in efficacy evaluation of programmed death-1 inhibitors / 上海交通大学学报（医学版）

Objective:To establish a lung cancer mouse model with humanized peripheral blood mononuclear cells (PBMC) expressing programmed death-ligand 1 (PD-L1), and study the role of the model in evaluating the efficacy of programmed death-1 (PD-1) inhibitors. Methods:Fresh biopsy tissue samples or tumor cells in malignant pleural effusion from the patients with advanced non-small cell lung cancer were inoculated subcutaneously in CB17-SCID mice to establish patient-derived xenograft (PDX) models. The expression of PD-L1 in PDX models was detected by immunohistochemistry. The mature human PBMC and PDX model tumor cells were mixed and then inoculated into NCG mice to establish a PDX model of lung cancer with humanized immunity, on which the efficacy of PD-1 inhibitor was verified. Results:Among the PDX models established by 16 clinical samples, 2 were strongly positive for PD-L1, 4 were positive, and the rest were negative. In the PDX model with strongly positive PD-L1, the tumor growth inhibition rate of cindilimab, an inhibitor of PD-1, was 82.6%, 21 days after the initial administration; in the PDX model with negative PD-L1, the inhibitor of PD-1 showed no antitumor activity. Conclusion:A PD-L1-expressing lung cancer mouse model with humanized immunity is successfully established and the efficacy of PD-1 inhibitor can be evaluated on the model.

A poor prognosis in human hepatocellular carcinoma is associated with low expression of DPP4

This study aimed to explore the prognostic role of dipeptidyl peptidase 4 (DPP4) expression in hepatocellular carcinoma (HCC). DPP4 expression was measured in formalin-fixed paraffin-embedded specimens that were gathered from 327 HCC patients. Immunohistochemistry analyses were utilized to examine DPP4 expression characteristics and prognostic values (overall survival (OS) and time to recurrence) of DDP4 in HCC tissues. In addition, a patient-derived xenograft (PDX) model was used to assess the correlation between DPP4 expression and tumor growth in vivo. DPP4 was expressed in low levels in HCC tissues in contrast to paired peritumoral tissues (38 cases were down-regulated in a total of 59 cases, 64.4%. P=0.0202). DPP4 expression was significantly correlated with TNM stage (P=0.038), tumor number (P=0.035), and vascular invasion (P=0.024), and significantly reduced in patients who were in TNM stages II and III-V, with multiple tumors, and with microvascular invasion compared to patients with TNM stage I, single tumor, and no microvascular invasion. Notably, HCC tissues with low expression of DPP4 had poor OS (P=0.016) compared with HCC tissues with high expression of DPP4, and results from PDX model showed that tumor growth was significantly faster in HCC patients that lowly expressed DPP4 compared to those with highly expressed DPP4. Our findings suggested that low levels of DPP4 could impact the aggressiveness of HCC and contribute to a poor prognosis.

Advances in the mouse models of myeloid leukemia / 生物医学工程学杂志

Mouse animal models are the most commonly used experimental tools in scientific research, which have been widely favored by researchers. The animal model of mouse leukemia appeared in the 1930s. During the past 90 years, researchers have developed various types of mouse leukemia models to simulate the development and treatment of human leukemia in order to promote effectively the elucidation of the molecular mechanism of leukemia' development and progression, as well as the development of targeted drugs for the treatment of leukemia. Considering that to myeloid leukemia, especially acute myeloid leukemia, there currently is no good clinical treatment, it is urgent to clarify its new molecular mechanism and develop new therapeutic targets. This review focuses on the various types of mouse models about myeloid leukemia used commonly in recent years, including mouse strains, myeloid leukemia cell types, and modeling methods, which are expected to provide a reference for relevant researchers to select animal models during myeloid leukemia research.

Research progress on osteosarcoma treatment in the precision medicine era / 中国肿瘤临床

With the rapid development of omics and big data technology, there have been multiple achievements with the use of pre-cision medicine for cancer treatment. Osteosarcoma, the most common primary malignant tumor of the skeletal system, primarily oc-curs in children and adolescents. Since the 1970s, surgical resection and chemotherapy have been the main treatments for osteosarco-ma; however, the survival rate for this type of cancer has been stagnant due to high genetic heterogeneity. Precision medicine can pro-vide a precise diagnosis and tailored treatments based on the patients’biological characteristics using techniques such as omics. Therefore, application of precision medicine is promising for studying osteosarcoma and improving patient survival rates. This study aims to systematically review the progress of precision medicine in advancing osteosarcoma treatment. In addition, it discusses the prospects and future direction of osteosarcoma precision treatment.

Establishment of patient derived xenograft model of high-grade mucinous carcinoma peritonei accompanied with signet ring cells and identification of biological characteristics / 中华肿瘤杂志

Objective@#To establish the patient derived xenograft (PDX) model of pseudomyxoma peritonei (PMP), and identify the key characteristics of tumor biology of this model, in order to provide a reliable model for studying the pathological mechanisms and new therapeutic strategies of PMP.@*Methods@#PMP tumor tissue was obtained from surgery and cut into pieces after washing. Then tumor pieces were implanted subcutaneously in BAL B/c-nu mice for 6 stable passages. In the 7th passage, tumor tissue was implanted orthotopically into abdomen. Subcutaneous tumor and orthotopic tumor were then homogenized to make tumor cell suspension, implanted into abdomen of 10 BAL B/c-nu mice through midline laparotomy, 100 μl for each. The key experimental parameters including body weight changes in the observation period, experimental peritoneal cancer index (ePCI) score at the autopsy, histopathological and immunohistochemical characteristics, and gene expression profiles by high-throughput whole-genome exon sequencing were detected and recorded.@*Results@#The successful rate of established orthotopic PDX model of human PMP was 100% (10/10). The animals showed smooth body weight increases after tumor inoculation until day 27, then the body weight began to decrease steadily. Widespread tumor dissemination of PMP tumor through the whole abdomen was found by autopsy, including the diaphragm, liver, spleen, stomach, kidney, parietal peritoneum, bowel and mesenterium. Gelatinous ascites was also observed in abdominopelvic cavity. The ePCI score ranged from 5 to 9, with a 8 of median ePCI. Histopathological studies showed peritoneal mucinous carcinomatosis accompanied with signet ring cells (PMCA-S), obvious tumor cell atypia and parenchymal invasion.Immunohistochemistry showed the expressions of MUC1, MUC2, MUC5AC, CEA, CA199, CK20, CDX-2 and Ki-67 were positive, MUC6, CK7 and p53 were negative. Whole-exome sequencing identified that the most significant genetic alteration is the exon10 missense mutation c. 1621A>C of KIT gene, the mutation abundance was 89.7%.@*Conclusion@#PDX model of PMCA-S is successfully established, which displays the characters of high-degree malignancy, high proliferation and strong aggressiveness.

Comparison of Clinical Features and Outcomes in Epithelial Ovarian Cancer according to Tumorigenicity in Patient-Derived Xenograft Models / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Although the use of xenograft models is increasing, few studies have compared the clinical features or outcomes of epithelial ovarian cancer (EOC) patients according to the tumorigenicity of engrafted specimens. The purpose of this study was to evaluate whether tumorigenicity was associated with the clinical features and outcomes of EOC patients. MATERIALS AND METHODS: Eighty-eight EOC patients who underwent primary or interval debulking surgery from June 2014 to December 2015 were included. Fresh tumor specimens were implanted subcutaneously on each flank of immunodeficient mice. Patient characteristics, progression-free survival (PFS), and germline mutation spectra were compared according to tumorigenicity. RESULTS: Xenografts were established successfully from 49 of 88 specimens. Tumorigenicity was associated with lymphovascular invasion and there was a propensity to engraft successfully with high-grade tumors. Tumors from patientswho underwent non-optimal (residual disease ≥ 1 cm) primary orinterval debulking surgery had a significantly greater propensity to achieve tumorigenicity than those who received optimal surgery. In addition, patients whose tumors became engrafted seemed to have a shorter PFS and more frequent germline mutations than patients whose tumors failed to engraft. Tumorigenicity was a significant factor for predicting PFS with advanced International Federation of Gynecology and Obstetrics stage and high-grade cancers. CONCLUSION: sTumorigenicity in a xenograft model was a strong prognostic factor and was associated with more aggressive tumors in EOC patients. Xenograft models can be useful as a preclinical tool to predict prognosis and could be applied to further pharmacologic and genomic studies on personalized treatments.

In Vivo Observation of Endothelial Cell-Assisted Vascularization in Pancreatic Cancer Xenograft Engineering

In this study, for better understanding of patient-derived xenograft (PDX) generation, angiogenic characteristics during PDX cancerous tissue generation was investigated with different initial cell seeding conditions in the hydrogel. We monitored the angiogenic changes during the formation of in vivo cancer cell line xenografts induced by endothelial cells. Our in vivo cancer tissue formation system was designed with the assistance of tissue engineering technology to mimic patient-derived xenograft formation. Endothelial cells and MIA PaCa-2 pancreatic carcinoma cells were encapsulated in fibrin gel at different mixing configurations and subcutaneously implanted into nude mice. To investigate the effect of the initial cancerous cell distribution in the fibrin gel, MIA PaCa-2 cells were encapsulated as a homogeneous cell distribution or as a cell aggregate, with endothelial cells homogeneously distributed in the fibrin gel. Histological observation of the explanted tissues after different implantation periods revealed three different stages: isolated vascular tubes, leaky blood vessels, and mature cancerous tissue formation. The in vivo engineered cancerous tissues had leaky blood vessels with low expression of the vascular tight junction marker CD31. Under our experimental conditions, complex cancer-like tissue formation was most successful when tumorous cells and endothelial cells were homogeneously mixed in the fibrin gel. The present study implies that tumorous xenograft tissue formation can be achieved with a low number of initial cells and that effective vascularization conditions can be attained with a limited volume of patient-derived cancer tissue. Endothelial cell-assisted vascularization can be a potent choice for the effective development of vascularized cancerous tissues for studying patient-derived xenografts, cancer angiogenesis, cancer metastasis, and anticancer drugs.

Comparison of the Genetic Alterations between Primary Colorectal Cancers and Their Corresponding Patient-Derived Xenograft Tissues

Patient-derived xenograft (PDX) models are useful tools for tumor biology research and testing the efficacy of candidate anticancer drugs targeting the druggable mutations identified in tumor tissue. However, it is still unknown how much of the genetic alterations identified in primary tumors are consistently detected in tumor tissues in the PDX model. In this study, we analyzed the genetic alterations of three primary colorectal cancers (CRCs) and matched xenograft tissues in PDX models using a next-generation sequencing cancer panel. Of the 17 somatic mutations identified from the three CRCs, 14 (82.4%) were consistently identified in both primary and xenograft tumors. The other three mutations identified in the primary tumor were not detected in the xenograft tumor tissue. There was no newly identified mutation in the xenograft tumor tissues. In addition to the somatic mutations, the copy number alteration profiles were also largely consistent between the primary tumor and xenograft tissue. All of these data suggest that the PDX tumor model preserves the majority of the key mutations detected in the primary tumor site. This study provides evidence that the PDX model is useful for testing targeted therapies in the clinical field and research on precision medicine.

A review of the establishment of patient-derived prostate cancer xenograft( PDX) model and screening of therapeutic drugs / 中国实验动物学报

The high-fidelity prostate tumor patient-derived xenograft ( PDX) model is the basis for studies of biology and pharmacotherapy of prostate cancer. However, the development and application of prostate tumor has been hampered by a low success rate of transplanted primary tumors in mice as most prostate cancers are highly relevant to hormones. The high-fidelity PDX model of prostate cancer better maintains the histopathology and molecular heterogeneity of the original tumor. Here, we review the improved method of establishing PDX model of prostate cancer, including the testosterone supplementation, the quality of the original tumor tissue as well as the stromal niche, and the application of commonly used therapeutic drugs, and to provide a theoretical basis for clinical studies of prostate tumor. These attempts are very important for development of new agents and research on mechanisms of prostate cancer. It will further promote the individualized treatment of prostate cancer.

Chemoterapeutic drug screening based on patient?derived pancreatic cancer xenograft(PDX)models / 中国实验动物学报

Objective To evaluate the therapeutic effect of chemotherapeutic drugs on pancreatic carcinoma based on patient-derived xenograft(PDX)models,and to screen an individualized treatment strategy. Methods Fresh human pancreatic carcinoma tissues were subcutaneously transplanted into nude mice to establish PDX models which could be stab-ly passaged. The traceability of PDX models was determined by STR analysis. The PDX models were treated with three dif-ferent clinical chemotherapeutic drugs oxaliplatin, gemcitabine and irinotecan, respectively, and the tumor volumes were measured at different times. The therapeutic effect of those drugs was assessed by TGD mathematical model and plasma CA19-9 test. Results The traceability of patient-derived xenograft samples was up to 99.99%. Compared with the con-trol group,the treatment with irinotecan and gemcitabine inhibited tumor growth significantly(P=0.001), and gemcit-abine had even better result. The minimum toxic effect in the mice was induced by irinotecan treatment,followed by gem-citabine treatment. Conclusions Pancreatic carcinoma PDX models are successfully established and can be stably pas-saged. Gemcitabine shows the most inhibitory effect on tumor growth based on TGD mathematical model assessment, and deserves to be recommended as the preferred drug for individual treatment of pancreatic carcinoma.

LC3-positive puncta increase in skeletal muscle of patient-derived xenograft mice / 体力科学

Loss of muscle tissues in cancer cachexia has been partly attributed to the activation of autophagy; however, because the experimental animal models involved only canonical cell lines, this conclusion cannot be confirmed until it is evaluated for different pathological conditions. Hence, in the present study, we histologically examined the punctate signal for LC3, an autophagosome marker, in patient-derived xenograft (PDX) mice. When 10 PDX mice grafted with colorectal cancer tissues were examined, their body weight, muscle (gastrocnemius) weight, and area of muscle fiber were all significantly lesser than those of control mice. In addition, immunofluorescence microscopy revealed that the number of LC3-positive puncta per muscle fiber or fiber area was significantly higher in the PDX mice than in control mice. These results indicate that the autophagy-lysosomal degradation system is involved in cancer cachexia-induced muscle wasting, and that PDX mice are a useful model for pathological analyses of cachexic muscle loss.

Establishment and application of a patient derived xenograft mouse model of liver cancer / 中国比较医学杂志

Objective To establish a patient-derived xenografts (PDX) mouse model of liver cancer (LC) and to explore its role in precision medicine.Methods PDX model was established by subcutaneous implantation of tumor tissues in NCG mice.The morphological structure of tumor tissue was exaimed using HE staining.Fifteen BALB/c nude mice were subcutaneously inoculated with tumor cell suspension from the PDX models.The xenograft mice were randomly divided into 5-fluorouracil (5-FU) group, sorafenib group and negative control group.The tumor volume and body weight of the tumor-bearing mice were measured regularly, the tumor inhibition rate was calculated and the curative effect was evaluated.Results The success rate was 33.3% (6/18) in the establishment of liver cancer PDX mouse model, and the model well retained the characteristics of the primary tumor.In one case of PDX mouse model, the tumor inhibition rates of 5-FU and sorafenib group were 63.7% and 29.6%, with a statistically significant differece between them (P< 0.05), and there was no significant difference between the sorafenib group and negative control group, consistent with clinical observation.Conclusions The PDX mouse model of liver cancer can maintain the histological structure of primary tumor, and can be applied to precision medicine for patients with liver cancer.

Patient-Derived Xenograft Models of Epithelial Ovarian Cancer for Preclinical Studies / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the primary patient tissues and evaluated their potential for use as a platform for translational EOC research. MATERIALS AND METHODS: We successfully established PDXs by subrenal capsule implantation of primary EOC tissues into female BALB/C-nude mice. The rate of successful PDX engraftment was 48.8% (22/45 cases). Hematoxylin and eosin staining and short tandem repeat analysis showed histopathological and genetic similarity between the PDX and primary patient tissues. RESULTS: Patients whose tumors were successfully engrafted in mice had significantly inferior overall survival when compared with those whose tumors failed to engraft (p=0.040). In preclinical tests of this model, we found that paclitaxel-carboplatin combination chemotherapy significantly deceased tumor weight in PDXs compared with the control treatment (p=0.013). Moreover, erlotinib treatment significantly decreased tumor weight in epidermal growth factor receptor–overexpressing PDX with clear cell histology (p=0.023). CONCLUSION: PDXs for EOC with histopathological and genetic stability can be efficiently developed by subrenal capsule implantation and have the potential to provide a promising platform for future translational research and precision medicine for EOC.

Relationship between tumorigenesis of human lung squamous carcinoma tissues in nude mice and the expression level of Ki-67 / 肿瘤

Objective: To establish the transplanted tumor models of human lung squamous cell carcinoma in nude mice, and to explore the relationship between the tumorigenicity of carcinoma tissues and Ki-67 expression level. Methods: Lung squamous cell carcinoma tissues were collected from 21 patients who underwent surgical resection at the Department of Thoracic Surgery of Anhui Provincial Hospital from August 2013 to January 2014. Lung carcinoma tissues were subcutaneously implanted into nude mice within 1 hour after surgical resection. The tumorigenicity of transplanted carcinoma tissues was observed, and the characteristics of patients with primary tumors that could form xenograft tumor (XG group) and couldn't form xenograft tumor (no-XG group) were compared retrospectively. The expressions of p63, cytokeratin 5/6 (CK5/6), thyoid transcription factor-1 (TTF-1) and Ki-67 were detected by immunohistochemistry, and the expression level of Ki-67 was semi-quantitatively analyzed by H-score method. The mutation status at the exons 18-21 of epidermal growth factor receptor (EGFR) gene was examined by amplification refractory mutation system (ARMS)-PCR. Results: Twelve (57.1%) xenograft models were succsessfully established after total 21 lung squamous cell carcinoma tissues were implanted into nude mice. The tumorigenicity of lung squamous cell carcinoma tissues in nude mice was correlated with differentiation (Z = -2.821, P = 0.005) and size (Z = -2.809, P = 0.005) of primary tumor in patients. High homogeneity of the expressions of p63, CK5/6, TTF-1 and Ki-67 as well as EGFR gene mutation status was found between xenograft tumors in nude mice and the lung squamous cell carcinoma tissues from the patients. The average H-score of the expression level of Ki-67 in XG group was 2.76±0.54, which was significantly higher than that in no-XG group (1.37±0.77) (t = 4.855, P = 0.001). Conclusion: The xenotransplantation models of patient-derived lung squamous cell carcinoma in nude mice were successfully established. Their tumorigenesis may be correlated with the expression level of Ki-67 in lung squamous cell carcinoma. This model system retains the basic biological characteristics of human lung squamous cancer, suggesting that it may provide a perfect platform for the research on human lung squamous cell carcinoma.