Diagnostic Value of GDF10 for the Tumorigenesis and Immune Infiltration in Lung Squamous Cell Carcinoma

Objective:Lung squamous cell carcinoma(LUSC)is associated with a low survival rate.Evidence suggests that bone morphogenetic proteins(BMPs)and their receptors(BMPRs)play crucial roles in tumorigenesis and progression.However,a comprehensive analysis of their role in LUSC is lacking.Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC.Methods:The“R/Limma”package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC,using data from TCGA,GTEx,and GEO databases.Concurrently,the“survminer”packages were employed to investigate their prognostic value and correlation with clinical features in LUSC.The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis(WGCNA).LASSO analysis was conducted to construct a prognostic risk model for LUSC.Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC.Furthermore,based on the tumor immune estimation resource database and tumor-immune system interaction database,the role of the core gene in the tumor microenvironment of LUSC was explored.Results:GDF10 had a significant correlation only with the pathological T stage of LUSC,and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC.A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes(HRASLS,HIST1H2BH,FLRT3,CHEK2,and ALPL)for LUSC.GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression.Conclusion:GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.

Prediction of Tumor Microenvironment Characteristics and Treatment Response in Lung Squamous Cell Carcinoma by Pseudogene OR7E47P-related Immune Genes

Objective Pseudogenes are initially regarded as nonfunctional genomic sequences,but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional activities.Olfactory receptor family 7 subfamily E member 47 pseudogene(OR7E47P)is expressed broadly in lung tissues and has been identified as a positive regulator in the tumor microenvironment(TME)of lung adenocarcinoma(LUAD).This study aimed to elucidate the correlation between OR7E47P and tumor immunity in lung squamous cell carcinoma(LUSC).Methods Clinical and molecular information from The Cancer Genome Atlas(TCGA)LUSC cohort was used to identify OR7E47P-related immune genes(ORIGs)by weighted gene correlation network analysis(WGCNA).Based on the ORIGs,2 OR7E47P clusters were identified using non-negative matrix factorization(NMF)clustering,and the stability of the clustering was tested by an extreme gradient boosting classifier(XGBoost).LASSO-Cox and stepwise regressions were applied to further select prognostic ORIGs and to construct a predictive model(ORPScore)for immunotherapy.The Botling cohorts and 8 immunotherapy cohorts(the Samstein,Braun,Jung,Gide,IMvigor210,Lauss,Van Allen,and Cho cohorts)were included as independent validation cohorts.Results OR7E47P expression was positively correlated with immune cell infiltration and enrichment of immune-related pathways in LUSC.A total of 57 ORIGs were identified to classify the patients into 2 OR7E47P clusters(Cluster 1 and Cluster 2)with distinct immune,mutation,and stromal programs.Compared to Cluster 1,Cluster 2 had more infiltration by immune and stromal cells,lower mutation rates of driver genes,and higher expression of immune-related proteins.The clustering performed well in the internal and 5 external validation cohorts.Based on the 7 ORIGs(HOPX,STX2,WFS,DUSP22,SLFN13,GGCT,and CCSER2),the ORPScore was constructed to predict the prognosis and the treatment response.In addition,the ORPScore was a better prognostic factor and correlated positively with the immunotherapeutic response in cancer patients.The area under the curve values ranged from 0.584 to 0.805 in the 6 independent immunotherapy cohorts.Conclusion Our study suggests a significant correlation between OR7E47P and TME modulation in LUSC.ORIGs can be applied to molecularly stratify patients,and the ORPScore may serve as a biomarker for clinical decision-making regarding individualized prognostication and immunotherapy.

PIK3CA mutation in Chinese patients with lung squamous cell carcinoma

Objective： To investigate PIK3CA mutation in Chinese patients with lung squamous cell carcinoma （LSCC） and explore their relationship with clinicopathological profiles. Methods： Tumor samples from 123 cases of LSCC were included in this study. PIK3CA mutations in exon 9 and 20 were screened by pyrosequencing and confirmed by clone sequencing or amplification refractory mutation system （ARMS）. Denaturing performance liquid chromatography （DHPLC） was employed for evaluation of EGFR mutation in exon 19, 21 and KRAS mutation. Results： PIK3CA mutations were found in 3 （2.4%） patients. The mutation type included E545K, E452Q and H1047R. Of these three patients, one coupled with EGFR mutation, and the other two coupled with PIK3CA amplification. All the three patients shared the same clinicopathologic characteristics： male, less than 60 years old, had smoke history, stage III and carried wild-type KRAS. Conclusions： The frequency of PIK3CA mutation is low in Chinese patients with LSCC. The mutational status of PIK3CA is not mutually exclusive to EGFR mutation.

Impact of Preoperative Serum Tumor Markers in Patients with Lung Squamous Cell Carcinoma

Background: Several previous researchers have investigated the prognostic value of serum tumor markers, especially carcinoembryonic antigen (CEA). Only a limited number of studies reported the usefulness of serum tumor markers for lung squamous cell carcinoma (SQ). We aimed to examine the significance of serum tumor markers for lung SQ. Methods: Eighty-five lung SQ patients who underwent surgery and followed more than 5-year were included. The ratios of 5-year survivors to all patients in groups with several clinicopathologic factors, including tumor markers, were compared. We also compared the clinicopathologic factors between central type and peripheral type SQ. Results: The majority of patients were male gender and current/ former smokers. Age, pN status, cytokeratin-19 fragment (CYFRA 21-1), squamous cell carcinoma antigen (SCC), and comorbid interstitial pneumonia (IP) were associated with the ratio of 5-year survivors significantly. When patients were compared based on tumor location, high p-stage and CYFRA 21-1 were related to central type SQ. Conclusion: Both SCC and CYFRA 21-1 appeared to be useful prognostic markers for patients with lung SQ. Furthermore, CYFRA 21-1 was related to central type SQ.

Significance of the Expression of Rho-GDP Dissociation Inhibitor β,γ in Lung Squamous Cell Carcinoma and Adenocarcinoma

Objective： To study the expression of Rho-GDP dissociation inhibitor β,γ （Rho-GDIβ, Rho-GDIγ） in lung squamous cell carcinoma and adenocarcinoma and its relationship with the expression of RhoC （Ras homologus oncogenes C） and clinicopathologic parameters. Methods： Western blot assay was employed for Rho-GDIβ, Rho-GDIγand RhoC in lung squamous cell carcinoma and adenocarcinoma and non-neoplastic lung tissues of 37 cases with fresh specimens. Results： The study showed that Rho-GDIβ, Rho-GDIγ and RhoC were expressed in lung cancer and non-neoplastic lung tissues, the level in lung cancer tissue was much higher than that in non-neoplastic tissues （P〈0.001）. In lung cancer, the expression of Rho-GDIβwas much higher in patients with lymph node metastasis （P=0.021）, and the expression of Rho-GDIγ was much higher in poorly differentiated tumor than in well-differentiated and moderately differentiated tumor, but both of them were not correlated with other clinicopathologic parameters. The expressions of Rho-GDIβ and Rho-GDIγ were not correlated with the expression of RhoC. Conclusion： In lung cancer, Rho-GDIβand Rho-GDIγ may play a role in the tumorigenesis, Rho-GDIβ may promote metastasis, and Rho-GDIγ may have some relationship with differentiation.

Mediastinal lymph node metastasis (N2 disease) based on the lobar location of lung squamous cell carcinoma

Aims:To explore the rule of N2 disease based on the lobar location of lung squamous cell carcinoma.Methods:A retrospective review of CT and clinical data of 438 patients with lung squamous cell carcinoma had been studied.To statistic the rate of N2 disease of different lobar location of lung squamous cell carcinoma.Results:The incidence and location of N2 disease of the 438 patients based on the location of the primary squamocellular carcinoma was as follows:for right upper lobe cancers,25% had N2 disease,most commonly in the 4R(36%) ;16% cases of right middle lobe had N2 and most commonly in the 4R(50%) and the 7th station(50%) ;30% cases of right lower lobe mass had N2 diseases and,most commonly in the 4R(31%) and the7th station(34%) ;left upper lobe,had 21% N2,most commonly in the 6th station(50%) ;and left lower lobe,24%,most commonly in the 7th station(43%) .Skip metastases(no N1,but N2) was appeared at left upper lobe lesions only.Patients with right-sided cancers have the similar incidence to have N2 disease(71/271,26%) as comparing with patients who had left-sided lesions(36/167,22%) (P>0.05) .Incidence of N2 diseases in right low lobe was more higher than other lobe,but have no significant difference compared to that of right upper lobe and left low lobe(P>0.05) .Incidence of N2 diseases in right middle lobe was the lowest when compared to that of other lobe(P<0.05) .Conclusion:There is a distinct predilection for the location of N2 disease based on the lobar location of primary lung squamous cell cancer.The location of lymph nodes metastasis had important rule in the classification and surgical dissection of lung squamous cell carcinoma.

Depletion of squalene epoxidase in synergy with glutathione peroxidase 4 inhibitor RSL3 overcomes oxidative stress resistance in lung squamous cell carcinoma

Background:Lung squamous cell carcinoma(Lusc)lacks effective targeted therapies and has a poor prognosis.Disruption of squalene epoxidase(SQLE)has been implicated in metabolic disorders and cancer.However,the role of SQLE as a monooxygenase involved in oxidativestressremainsunclear.Methods:We analyzed the expression and prognosis of lung adenocarcinoma(LUAD)and LUSC samples from GEO and TCGA databases.The proliferative activity of the tumors after intervention of SQLE was verified by cell and animal experiments.JC-1 assay,flow cytometry,and Western blot were used to show changes in apoptosis after intervention of sQLE.Flow cytometry and fluorescence assay of ROs levels were used to indicate oxidative stress status.Results:We investigated the unique role of SQLE expression in the diagnosis and prognosis prediction of LUSC.Knockdown of SQLE or treatment with the SQLE inhibitor terbinafine can suppress the proliferation of LUsC cells by inducing apoptosis and reactive oxygen species accumulation.However,depletion of SQLE also results in the impairment of lipid peroxidation and ferroptosis resistance such as upregulation of glutathione peroxidase 4.Therefore,prevention of SQLE in synergy with glutathione peroxidase 4 inhibitor RSL3 effectively mitigates the proliferation and growth of LUSC.Conclusion:Our study indicates that the low expression of sQLE employs adaptive survival through regulating the balance of apoptosis and ferroptosis resistance.In future,the combinational therapy of targeting sQLE and ferroptosis could be a promising approach in treating LUSC.

Different types of tumor microvessels in stageⅠ-ⅢA squamous cell lung cancer and their clinical significance

BACKGROUND Lung cancer(LC)is the leading cause of morbidity and mortality among malignant neoplasms.Improving the diagnosis and treatment of LC remains an urgent task of modern oncology.Previously,we established that in gastric,breast and cervical cancer,tumor microvessels(MVs)differ in morphology and have different prognostic significance.The connection between different types of tumor MVs and the progression of LC is not well understood.AIM To evaluate the morphological features and clinical significance of tumor MVs in lung squamous cell carcinoma(LUSC).METHODS A single-center retrospective cohort study examined medical records and archival paraffin blocks of 62 and 180 patients with stage I-IIIA LUSC in the training and main cohorts,respectively.All patients underwent radical surgery(R0)at the Orenburg Regional Cancer Clinic from May/20/2009 to December/14/2021.Tumor sections were routinely processed,and routine Mayer's hematoxylin and eosin staining and immunohistochemical staining for cluster of differentiation 34(CD34),podoplanin,Snail and hypoxia-inducible factor-1 alpha were performed.The morphological features of different types of tumor MVs,tumor parenchyma and stroma were studied according to clinicopathological characteristics and LUSC prognosis.Statistical analysis was performed using Statistica 10.0 software.Univariate and multivariate logistic regression analyses were performed to identify potential risk factors for LUSC metastasis to regional lymph nodes(RLNs)and disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with and without metastases in RLNs and those with and without disease recurrence.The effectiveness of the predictive models was assessed by the area under the curve.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.A value of P<0.05 was considered to indicate statistical significance.RESULTS Depending on the morphology,we classified tumor vessels into the following types:normal MVs,dilated capillaries(DCs),atypical DCs,DCs with weak expression of CD34,"contact-type"DCs,structures with partial endothelial linings,capillaries in the tumor solid component and lymphatic vessels in lymphoid and polymorphocellular infiltrates.We also evaluated the presence of loose,fine fibrous connective tissue(LFFCT)and retraction clefts in the tumor stroma,tumor spread into the alveolar air spaces(AASs)and fragmentation of the tumor solid component.According to multivariate analysis,the independent predictors of LUSC metastasis in RLNs were central tumor location(P<0.00001),the presence of retraction clefts(P=0.003),capillaries in the tumor solid component(P=0.023)and fragmentation in the tumor solid component(P=0.009),whereas the independent predictors of LUSC recurrence were tumor grade 3(G3)(P=0.001),stage N2(P=0.016),the presence of LFFCT in the tumor stroma(P<0.00001),fragmentation of the tumor solid component(P=0.0001),and the absence of tumor spread through the AASs(P=0.0083).CONCLUSION The results obtained confirm the correctness of our previously proposed classification of different types of tumor vessels and may contribute to improving the diagnosis and treatment of LUSC.

Predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa squamous cell lung cancer:A retrospective analysis

BACKGROUND Lung cancer(LC)is a global medical,social and economic problem and is one of the most common cancers and the leading cause of mortality from malignant neoplasms.LC is characterized by an aggressive course,and in the presence of disease recurrence risk factors,patients,even at an early stage,may be indicated for adjuvant therapy to improve survival.However,combined treatment does not always guarantee a favorable prognosis.In this regard,establishing predictors of LC recurrence is highly important both for determining the optimal treatment plan for the patients and for evaluating its effectiveness.AIM To establish predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa lung squamous cell carcinoma(LSCC).METHODS A retrospective case-control cohort study included 69 patients with LSCC who underwent radical surgery at the Orenburg Regional Clinical Oncology Center from 2009 to 2018.Postoperatively,all patients received adjuvant chemotherapy.Histological samples of the resected lung were stained with Mayer's hematoxylin and eosin and examined under a light microscope.Univariate and multivariate analyses were used to identify predictors associated with the risk of disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with a high risk of disease recurrence and those with a low risk of disease recurrence.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.Differences were considered to be significant at P<0.05.RESULTS The following predictors of a high risk of disease recurrence in patients with stage IIb-IIa LSCC were established:a low degree of tumor differentiation[odds ratio(OR)=7.94,95%CI=1.08-135.81,P=0.049];metastases in regional lymph nodes(OR=5.67,95%CI=1.09-36.54,P=0.048);the presence of loose,fine-fiber connective tissue in the tumor stroma(OR=21.70,95%CI=4.27-110.38,P=0.0002);and fragmentation of the tumor solid component(OR=2.53,95%CI=1.01-12.23,P=0.049).The area under the curve of the predictive model was 0.846(95%CI=0.73-0.96,P<0.0001).The sensitivity,accuracy and specificity of the method were 91.8%,86.9%and 75.0%,respectively.In the group of patients with a low risk of LSCC recurrence,the 1-,2-and 5-year disease-free survival(DFS)rates were 84.2%,84.2%and 75.8%,respectively,while in the group with a high risk of LSCC recurrence the DFS rates were 71.7%,40.1%and 8.2%,respectively(P<0.00001).Accordingly,in the first group of patients,the 1-,2-and 5-year overall survival(OS)rates were 94.7%,82.5%and 82.5%,respectively,while in the second group of patients,the OS rates were 89.8%,80.1%and 10.3%,respectively(P<0.00001).CONCLUSION The developed method allows us to identify a group of patients at high risk of disease recurrence and to adjust to ongoing treatment.

Imbalanced expression of mitogen-activated protein kinase phosphatase-1 and phosphorylated extracellular signal-regulated kinases in lung squamous cell carcinoma

Objective： Mitogen-activated protein kinases （MAPKs） are correlated with a more malignant phenotype in many cancers. This study was designed to evaluate the predictive value of the expression of MAPK phosphatase-1 （MKP-1） and phosphorylated extracellular signal-regulated kinase 1/2 （p-ERKl/2）, as the key regulatory mechanism of the MAPKs, in lung squamous cell carcinoma （SCC）. Methods： We assessed the expressions of MKP-1 and p-ERK1/2 in twenty subjects at different differentiation degree of SCC and five normal lungs by immunohistochemistry and real-time reverse transcriptase polymerase chain reaction （RT-PCR） analysis. Results： Immunohistochemistry and real-time RT-PCR assay showed that the expression of MKP-1 was gradually decreased as tissue type went from normal lung tissues to increasingly undifferentiated carcinoma, and it was negatively correlated with tumor differentiation （P〈0.01）. However, the expression of p-ERK1/2 or ERKl/2 was gradually increased as tissue type went from normal lung tissues to increasingly undifferentiated carcinoma, and it was positively correlated with tumor differentiation （P〈0.01）. Conclusions： Our data indicates the relevance of MKP-1 and p-ERK1/2 in SCC as a potential positive and negative prognostic factor. The imbalanced expression of MKP-1 and p-ERKl/2 may play a role in the development of SCC and these two molecules may be new targets for the therapy and prognosis of SCC.

Integrative Analyses of Lung Squamous Cell Carcinoma in Ten Chinese Patients with Transcriptome Sequencing

Few effective therapies have been developed for the treatment of lung squamous cell carcinoma （SQCC）, in part due to a lack of un- derstanding regarding the mechanisms underlying the initiation and development of this disease. Whole transcriptome sequencing not only provides insight into the expression of all transcribed genes, but offers an efficient approach for identifying genetic variations, including gene fusions, mutations and alternative splicing. In this study, we performed whole transcriptome sequencing of 10 patients with stage IIIA lung SQCC, and discovered a large number of single nucleotide variants （SNVs： mean of 12.2 SNVs/Mb）, with C〉T/G〉A and A〉G/T〉C transitions being the most frequently observed. Additionally, a total of 132 gene fusions were identified based upon TopHat alignments, 70.5% （93/132） of which occurred as a result of intra-chromosomal rearrangements. Based on the number of supporting reads for each fusion, we further validated 20 of the 26 top gene fusions by RT-PCR and Sanger sequencing. Taken together, these data provide an in-depth view of transcriptional alterations in lung SQCC patients, and may be useful for identification of new therapeutic targets.

Lung squamous cell carcinoma combined with tuberculous pleurisy

A58-year old male patient was admitted to our .hospital with repeated coughing, expectoration withblood in the sputum for more than 10 months, bilateral wrists and ankles with pain and afternoon low fever, chest tightness and shortness of breath in the latest one month. The patient had a history of joint pain for more than 3 years without special treatment. He had a smoking history for more than 30 years with 10 cigarettes a day. He had no family tumor history. Physical examination： T 38.5℃, P 100/min, R 22/min, blood pressure （BP） 107/77 mmHg; the double upper fingers visible clubbing, bilateral supraclavicular lymph node not feelable, left inferior pulmonary respiratory sounds disappeared, and wet and dry sounds not heard.

REVERSION OF MALIGNANT PHENOTYPES OF HUMAN LUNG SQUAMOUS CARCINOMA CELLS BY ORNITHINE DECARBOXYLASE ANTISENSE RNA

Abnormally elevated activity of ornithine decarboxylase (ODC), and subsequent polyamine accumulation are intimately associated with the genesis.development and metastasis of cancer. In the present study, to control the growth of tumor cells, ODC antisense RNA was used to transfect human lung squamous carcinoma cell line LTEP-78. Compared with the parental cells, growth of the antisense transfected LTEP-78 cells arrested in G0/Gl phase and colony formation in soft agarose and tumorigenicity in nude mice were significantly reduced. Nucleic acid hybridization demonstrated that the transfectants expressed a high level of ODC antisense RNA and a significantly reduced level of endogenous ODC mRNA.The results suggest that the reversion of malignant phenotypes of human lung squamous carcinoma cells transfected with ODC antisense RNA is associated with the inhibition of polyamine biosynthesis.

Expressions of FEZ1 and Survivin, and their significance in small cell lung cancer and squamous cell lung carcinoma

Objective： To detect the expressions of FEZ1 and Survivin in small cell lung cancer （SOLO） and poorly differentiated squamous cell carcinoma （PDSCC）, and to approach a theoretical basis for clinical diagnosis and treatment. Methods： Immunohistochemical and flow cytometry method were used to detect the expressions of FEZ1 and Survivin. Apoptosis ratio and cell proliferation index in normal lung tissue, SCLC and PDSCC were analyzed. Results： The expressions of FEZ1 and Survivin were significantly different between SCLC and PDSCC （P 〈 0.05）. The apoptosis ratio and proliferation index of normal lung tissue were lower than those of PDSCC and SOLO, with a significant difference （P 〈 0.05）. Conclusion： The expressions of FEZ1 and Survivin are significantly different between SCLC and PDSCC, indicating that detecting the expressions of the two indexes may be helpful for clinical diagnosis.

Solitary pancreatic metastasis from squamous cell lung carcinoma: A case report and review of literature

BACKGROUND Pancreatic metastases from squamous cell lung carcinoma(SCLC)are unusual.These lesions are often asymptomatic and detected incidentally or during followup investigations,occasionally several years after removal of the primary tumor.CASE SUMMARY A 56-year-old male with SCLC developed jaundice 1 mo after the cancer diagnosis.An abdominal computed tomography(CT)scan showed a mass in the pancreatic head with distention of both intra-and extrahepatic biliary ducts.Endoscopic retrograde cholangiopancreatography and sphincterotomy were performed first,culminating with plastic biliary stent placement.Cytological examination of the pancreatic mass sample collected by fine-needle aspiration(FNA)under endoscopic ultrasound(EUS)guidance revealed the presence of malignant cells compatible with well-differentiated squamous cell carcinoma.After liver function normalized,chemotherapy was initiated with carboplatin and paclitaxel;however,4 d later,the patient presented dysphagia.Cervico-thoracoabdominal CT showed tracheoesophageal fistula and stent migration.After replacement with a 10 cm/10 mm uncovered metallic biliary stent and treatment of the tracheoesophageal fistula with a fully covered esophageal stent,the patient was able to start oral feeding progressively.He died 9 mo after the initial diagnosis.CONCLUSION The diagnosis of pancreatic metastasis from SCLC is challenging for clinicians.EUS-FNA is the primary exam for confirmatory diagnosis.

Perioperative Nursing Care for Patients with Lung Cancer Undergoing Total Pneumonectomy

Objectives: To explore the perioperative nursing care for lung cancer patients undergoing total pneumonectomy, and to promote their rehabilitation. Methods: We will provide preoperative assessment and education in the aspects of respiratory function, diet, and psychology to patients undergoing total pneumonectomy, and provide continuous postoperative management about posture, fluid, and respiratory to help patients diagnosed with lung squamous cell carcinoma and underwent total pneumonectomy to reduce their postoperative complications and improve their overall quality of life. Results: 78.9% of lung cancer patients who underwent total pneumonectomy achieved a better outcome and prognosis by receiving the above nursing program. Conclusion: With large lung cancer tumors, the surgical trauma is highly invasive and the resection is extensive. Management of the patient’s respiratory tract is the focus of perioperative nursing and the key to preventing the development of related postoperative complications.

Adenocarcinoma transformed into squamous cell carcinoma in non-small cell lung cancer

Non-small cell lung cancer(NSCLC)is the most common form of lung cancer which remains the deadliest malignancy worldwide(Siegel et al.,2019).In general,NSCLC can be divided into several subtypes,including adenocarcinoma(ADC),squamous cell carcinoma(SCC),adeno-squamous cell carcinoma(AD-SCC)and large cell carcinoma(LCC).

EGFR mutation--a commonly neglected mutation in squamous cell lung carcinoma

Lung cancer is the leading cause of cancer-related death worldwide.Advances in molecular biology have unveiled various targetable mutations with epidermal growth factor receptor(EGFR)being most common.EGFR testing is recommended for all locally advanced or metastatic adenocarcinoma lungs but recommendation in squamous histology is uncertain.However,just on the basis of histology,EGFR testing should not be withheld in patients diagnosed as squamous cell cancer on small biopsy,in females,never smokers and Asians.We report two cases with squamous cell lung cancer diagnosed on small biopsy,in non smoker females with EGFR mutations emphasizing the importance of testing in such population.

Paclitaxel liposome for injection (Lipusu) plus cisplatin versus gemcitabine plus cisplatin in the first-line treatment of locally advanced or metastatic lung squamous cell carcinoma: A multicenter, randomized, open-label, parallel controlled clinical study

Background:Lipusu is the first commercialized liposomal formulation of pacli-taxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma(LSCC)in a small-scale study.Here,we conducted a multicenter,randomized,phase 3 study to compare the efficacy and safety of cis-platin plus Lipusu(LP)versus cisplatin plus gemcitabine(GP)as first-line treat-ment in locally advanced or metastatic LSCC.Methods:Patients enrolled were aged between 18 to 75 years,had locally advanced(clinical stage IIIB,ineligible for concurrent chemoradiation or surgery)or metastatic(Stage IV)LSCC,had no previous systemic chemother-apy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors(version 1.1)before administration of the trial drug.The primary endpoint was progression-free survival(PFS).The secondary endpoints included objective response rate(ORR),disease control rate(DCR),overall survival(OS),and safety profiles.To explore the possible predictive value of plasma cytokines for LP treatment,plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology.The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses.Results:The median duration of follow-up was 15.4 months.237 patients in the LP group and 253 patients in the GP group were included in the per protocol set(PPS).In the PPS,the median PFS was 5.2 months versus 5.5 months in the LP and GP group(hazard rtio[HR]:1.03,P=0.742)respectively.The median OS was 14.6 months versus 12.5 months in the LP and GP group(HR:0.83,P=0.215).The ORR(41.8%versus 45.9%,P=0.412)and DCR(90.3%versus 88.1%,P=0.443)were also similar between the LP and GP group.A significantly lower proportion of patients in the LP group experienced adverse events(AEs)leading to treatment interruptions(10.9%versus 26.4%,P<0.001)or treatment termination(14.3%versus 23.1%,P=0.011).The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR,and 15 cytokines were associated with improved PFS,with 14 cytokines,including TNF-a,IFN-y,IL-6,and IL-8,demonstrating an overlapping trend.Conclusion:The LP regimen demonstrated similar PFS,OS,ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles.The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen.