Comparison between solid pseudopapillary neoplasms of the pancreas and pancreatic ductal adenocarcinoma with cystic changes using computed tomography

BACKGROUND Solid pseudopapillary neoplasms of the pancreas(SPN)share similar imaging findings with pancreatic ductal adenocarcinoma with cystic changes(PDAC with cystic changes),which may result in unnecessary surgery.AIM To investigate the value of computed tomography(CT)in differentiation of SPN from PDAC with cystic changes.METHODS This study retrospectively analyzed the clinical and imaging findings of 32 patients diagnosed with SPN and 14 patients diagnosed with PDAC exhibiting cystic changes,confirmed through pathological diagnosis.Quantitative and qualitative analysis was performed,including assessment of age,sex,tumor size,shape,margin,density,enhancement pattern,CT values of tumors,CT contrast enhancement ratios,“floating cloud sign,”calcification,main pancreatic duct dilatation,pancreatic atrophy,and peripancreatic invasion or distal metastasis.Multivariate logistic regression analysis was used to identify relevant features to differentiate between SPN and PDAC with cystic changes,and receiver operating characteristic curves were obtained to evaluate the diagnostic performance of each variable and their combination.RESULTS When compared to PDAC with cystic changes,SPN had a lower age(32 years vs 64 years,P<0.05)and a slightly larger size(5.41 cm vs 3.90 cm,P<0.05).SPN had a higher frequency of“floating cloud sign”and peripancreatic invasion or distal metastasis than PDAC with cystic changes(both P<0.05).No significant difference was found with respect to sex,tumor location,shape,margin,density,main pancreatic duct dilatation,calcification,pancreatic atrophy,enhancement pattern,CT values of tumors,or CT contrast enhancement ratios between the two groups(all P>0.05).The area under the receiver operating characteristic curve of the combination was 0.833(95%confidence interval:0.708-0.957)with 78.6%sensitivity,81.3%specificity,and 80.4%accuracy in differentiation of SPN from PDAC with cystic changes.CONCLUSION A larger tumor size,“floating cloud sign,”and peripancreatic invasion or distal metastasis are useful CT imaging features that are more common in SPN and may help discriminate SPN from PDAC with cystic changes.

Is endoscopic submucosal dissection safe for papillary adenocarcinoma of the stomach?

AIM: To identify the clinicopathological predictors of lymph node(LN) metastasis and evaluate the outcomes of endoscopic submucosal dissection(ESD) in papillary adenocarcinoma-type early gastric cancers(EGCs).METHODS: From January 2005 to May 2013, 49 patients who underwent surgical operation and 24 patients who underwent ESD for papillary adenocarcinomatype EGC were enrolled to identify clinicopathological characteristics and predictive factors of LN metastasis and to evaluate the outcomes of ESD for papillary adenocarcinoma-type EGC.RESULTS: Most papillary adenocarcinoma-type EGCs were located in the lower third of the stomach and had an elevated macroscopic shape. The overall prevalence of LN metastasis was 18.3%(9/49). The presence of lymphovascular invasion was found to be a predictor of LN metastasis(P = 0.016). According to current indication criteria of ESD, 6 and 11 of the 49 patients had absolute and expanded indications for ESD, respectively. Two patients(11.8%) with expanded indication for ESD had LN metastasis. Of the 24 patients who underwent ESD, 13(54%) achieved out-of-ESD indication, with 9 of those 13 patients undergoing surgical operation due to non-curative resection. CONCLUSION: The use of ESD should be carefully considered for papillary adenocarcinoma-type EGC with suspected ESD indication after pre-treatment work-up because of the higher frequency of LN metastasis and additional surgeries.

Concomitant pancreatic adenocarcinoma in a patient with branch-duct intraductal papillary mucinous neoplasm

Branch duct intraductal papillary mucinous neoplasms(BD-IPMN) are pre-malignant pancreatic cystic lesions which carry a small risk of malignant transformation within the cyst. Guidelines exist with respect to surveillance of the cysts using computed tomography, magnetic resonance imaging, and/or endoscopic ultrasound(EUS). There are reports that patients with IPMNs are at increased risk of developing pancreatic adenocarcinoma, which arises in an area separate to the IPMNs. We present two cases of pancreatic adenocarcinoma arising within the parenchyma, distinct from the IPMN-associated cyst, identified with EUS. This case report highlights that patients with BD-IPMN are at increased risk for pancreatic adenocarcinoma separate from the cyst and also the importance for endosonographers to carefully survey the rest of the pancreatic parenchyma separate from the cyst in order to identify small pancreatic adenocarcinomas.

Unusual Cystic and Papillary Appearance of Brain Metastasis from Papillary Lung Adenocarcinoma on MRI. Radiologic-Pathologic Correlations in Two Similar Cases

We report two cases of brain metastasis from a lung adenocarcinoma. Magnetic Resonance Imaging (MRI) appearance was closely correlated with the macroscopic and microscopic findings that showed multiples nodules of a well-differentiated papillary adenocarcinoma with secreting tubules, surrounded by mucoid fluid.

Synchronous primary duodenal papillary adenocarcinoma and gallbladder carcinoma:A case report and review of literature

BACKGROUND Synchronous primary cancers(SPCs) have become increasingly frequent over the past decade.However,the coexistence of duodenal papillary and gallbladder cancers is rare,and such cases have not been previously reported in the English literature.Here,we describe an SPC case with duodenal papilla and gallbladder cancers and its diagnosis and successful management.CASE SUMMARY A 68-year-old Chinese man was admitted to our hospital with the chief complaint of dyspepsia for the past month.Contrast-enhanced computed tomography of the abdomen performed at the local hospital revealed dilatation of the bile and pancreatic ducts and a space-occupying lesion in the duodenal papilla.Endoscopy revealed a tumor protruding from the duodenal papilla.Pathological findings for the biopsied tissue revealed tubular villous growth with moderate heterogeneous hyperplasia.Surgical treatment was selected.Macroscopic examination of this surgical specimen revealed a 2-cm papillary tumor and another tumor protruding by 0.5 cm in the gallbladder neck duct.Intraoperative rapid pathology identified adenocarcinoma in the gallbladder neck duct and tubular villous adenoma with high-grade intraepithelial neoplasia and local canceration in the duodenal papilla.After an uneventful postoperative recovery,the patient was discharged without complications.CONCLUSION It is essential for clinicians and pathologists to maintain a high degree of suspicion while evaluating such synchronous cancers.

Intraductal papillary bile duct adenocarcinoma and gastrointestinal stromal tumor in a case of neurofibromatosis type 1

We report our experience with a synchronous case of gastrointestinal stromal tumor(GIST) and intraductal papillary neoplasm of the bile duct(IPNB) in anelderly woman with neurofibromatosis type 1(NF-1). A 72-year-old woman presented with a 2-mo history of right upper abdominal pain unrelated to diet and indigestion. Fourteen years earlier, she had been diagnosed with NF-1, which manifested as café au lait spots and multiple nodules on the skin. Computed tomography(CT) revealed a multilocular low-density mass with septation, and mural nodules in the right hepatic lobe, as well as a 1.7-cm-sized well-demarcated enhancing mass in the third portion of the duodenum. The patient subsequently underwent right hepatectomy and duodenal wedge resection. We present here the first report of a case involving a synchronous IPNB and GIST in a patient with NF-1. Our findings demonstrate the possibility of various tumors in NF-1 patients and the importance of diagnosis at an early

Papillary Adenocarcinoma of the Thyroid in Ectopic Intrathoracic Goiter:One Case Report

Case ReportA 58-year-old male patient presented to our department for surgical management of a right neck nodule and low fever over the past 2 weeks. Preoperative evaluation, which included chest CT scan, MRI and scintigraphy （^99mTc）, revealed round and clear boundary intrathoracic ectopic thyroid tissue at the right side of the anterior mediastinum and an enlarged lymph node in the right neck. The preoperative general image diagnosis concluded a malignant ectopic intrathoracic goiter （Figs. 1-3）. The lymph node biopsy confirmed a metastatic papillary adenocarcinoma of the thyroid.. The tumor was resected via a cervical collar incision （Fig.4）. Bilateral hemithyroidectomy and cervical lymph node dissection were also performed. We noticed that the intrathoracic thyroid was not connected to the cervical thyroid. Blood was supplied from the intrathoracic vessels, thereby establishing the diagnosis of an ectopic intrathoracic thyroid. Final pathologic diagnosis was a papillary adenocarcinoma of the thyroid in an ectopic intrathoarcic goiter with involved lymph node. The postoperative course was uneventful.

Furmonertinib re-challenge for epidermal growth factor receptormutant lung adenocarcinoma after osimertinib-induced interstitial lung disease:A case report

BACKGROUND Most non-small cell lung cancer patients have epidermal growth factor receptor(EGFR)activating mutations,such as exon 19 deletion and exon 21 replacement mutations.Osimertinib is a third-generation EGFR-tyrosine kinase inhibitors ap-proved for the treatment of lung cancer patients carrying EGFR activating mu-tations.Osimertinib-induced interstitial lung disease(ILD)is a rare and poten-tially fatal pulmonary toxic manifestation of drug therapy.At present,there is no international consensus on the risks and treatment of the osimertinib-induced ILD.CASE SUMMARY We report a case of a 56-year-old woman who was diagnosed with lung adenocar-cinoma with lung hilum,mediastinal lymph nodes and brain metastases(T4N3-M1c stage IVB).The patient received targeted treatment with osimertinib after radiotherapy and chemotherapy.But she developed ILD after osimertinib treat-ment.Following active symptomatic treatment and hormone treatment,the lung injury alleviated.The patient was retreated with furmonertinib combined with prednisone and did not experience ILD again.So far,she has survived for 14 months without disease progression.CONCLUSION Retreatment with furmonertinib under prednisone could be considered as an effective therapeutic option after risk-benefit assessment for EGFR-mutant lung adenocarcinoma patients.

Concurrent occurrence of adenocarcinoma and urothelial carcinoma of the prostate:Coexistence mechanisms from multiple perspectives

This article discusses the coexistence of prostate adenocarcinoma and prostate urothelial carcinoma.Combining existing literature and research results,the potential mechanisms of the co-occurrence of these two cancers are explored,including the role of androgen receptor,gene mutations,and their complex interactions in cell signaling pathways,etc.Also,the hypothesis of prostate cancer transformation into urothelial carcinoma is explained from some perspectives,including tumor multipotent stem cell differentiation,epithelial-mesenchymal transition,mesenchymal-epithelial transition,and other mechanisms.Ultimately,the goal is to provide more accurate diagnoses and more personalized treatments in clinical practice,as well as to lay the foundation for improving patient prognoses in the future.

Gastrointestinal bleeding due to small bowel metastasis from lung adenocarcinoma:A case report

BACKGROUND Lung cancer is the most prevalent malignant tumor in human body,and is characterized by a high level of malignancy.The most common metastatic sites include the liver,bone,brain,and adrenal gland,while lung cancer resulting in gastrointestinal tract metastasis is uncommon.CASE SUMMARY A 74-years-old man with lung cancer was hospitalized owing to blood in the stool,The cause was identified as metastasis to the small intestine,and the patient subsequently underwent radical resection of the small intestine tumor.Currently,the overall condition of the patient is good,and undergoing combined chemotherapy.CONCLUSION Early intervention in patients with metastatic tumors can significantly improve prognosis.

Long-term survival outcomes of duodenal adenocarcinoma:A cohort study with 15-year single-center experience

BACKGROUND Duodenal adenocarcinoma(DA),a rare gastrointestinal malignancy,lacks clear natural history and management strategies.This study aimed to investigate the long-term outcomes of patients with DA,focusing on long-term survival and the impact of tumor characteristics,surgery,and adjuvant therapy.AIM To bridge this knowledge gap,we conducted a hospital-based cohort study in our 15-year experience with DA aimed at investigating the long-term outcomes of the patients with DA,along with analyzing the impact of the tumor characteristics,operations and adjuvant therapy on survival outcomes.METHODS A retrospective analysis of 208 patients diagnosed with non-ampullary DA at a single institution between 2009 and 2023 was performed.This study used SPSS 26.0 software to make a comprehensive statistical analysis of demographic characteristics,clinical presentation,treatment modalities,and survival outcomes.The effectiveness of surgical resection and adjuvant therapy in 5-year oval survival(OS)and disease-free survival was evaluated using Kaplan-Meier survival curves,the Cox proportional hazards model,and statistical comparisons of survival distributions.RESULTS The median OS time for the cohort was 39 months,with 3-and 5-year OS rates of 51.2%and 43.6%,respectively.Radical resection was performed in 82.6%of cases,and was significantly associated with an improved 5-year OS,with a rate of 57.8%.Adjuvant therapy showed a survival benefit in the specific patient subsets,particularly in tumor stage Ⅱ or Ⅲ tumors,with an improved OS.Adjuvant therapy(hazard ratio=2.71,95%confidence interval:1.30-5.62,P=0.008),pancreatic invasion and advanced tumor stage were identified as significant predictors of OS in multivariate analyses.CONCLUSION Radical operation for DA is associated with a remarkable improvement in the 5-year OS.Importantly,postoperative adjuvant therapy can significantly prolong the OS time in patients with radical operation,especially in patients with stage III.It highlights the necessity for early diagnosis,tailored surgical approaches,and a nuanced understanding of the role of adjuvant therapy.

Improving predictive accuracy of early recurrence in pancreatic ductal adenocarcinoma:Role of postoperative serum tumor markers

In a recent study by He et al,the nomogram integrates postoperative serum tumor markers such as carbohydrate antigen 19-9 and carcinoembryonic antigen,thereby improving the accuracy of identifying high-risk patients compared to relying solely on preoperative markers,which has significant implications for customizing adjuvant therapy and potentially improving outcomes for this aggressive form of cancer.However,the study’s single-center design and short follow-up period may limit the generalizability of its findings and potentially introduce reporting bias.Future studies could consider additional confounding factors,such as adjuvant chemotherapy and variations in surgical techniques,to improve the model’s accuracy.Furthermore,it would be valuable to validate the nomogram in broader,prospective cohorts and explore the inclusion of additional markers like circulating tumor DNA to refine further its predictive power and applicability across diverse patient populations.

Clinical significance of Ki-67 in patients with lung adenocarcinoma in situ complicated by type 2 diabetes

BACKGROUND The increasing number of type 2 diabetes mellitus(T2DM)patients leads to higher rates of morbidity and mortality related to lung cancer.AIM To investigate the utility of the proliferating cell nuclear antigen Ki-67 in patients with lung adenocarcinoma in situ(AIS)complicated by T2DM.METHODS One hundred patients with AIS and T2DM(group A),100 patients with AIS alone(group B),and 60 patients with benign lung lesions(group C)admitted to the Department of Thoracic Surgery and Endocrinology of the First Affiliated Hospital of Soochow University from November 2021 to December 2022 were enrolled.Ki-67 expression was compared among the groups.RESULTS Group A had significantly higher levels of fasting plasma glucose(FPG),total cholesterol(TC),total triglyceride,low-density lipoprotein cholesterol,glycosylated hemoglobin(HbA1c),and insulin than groups B and C(P<0.01).Meanwhile,group B had higher insulin levels than group C(P<0.01).Group A exhibited a significantly higher average Ki-67 positivity rate than group B(P<0.01).The Ki-67 positivity rate in group A was 86.87%,while the positivity rate in group B was 77%.Ki-67 was positively correlated with FPG(P<0.01)and HbA1c levels(P<0.01).Ki-67,FBG,insulin,HbA1c,high-density lipoprotein cholesterol and TC were independent factors for patients with AIS complicated by T2DM.Chen K et al.Ki67 in patients with AIS complicated by T2DM WJD https://www.wjgnet.com 2 February 15,2025 Volume 16 Issue 2 CONCLUSION Ki-67 expression was higher in patients with AIS complicated by T2DM than in patients with AIS alone.Therefore,detecting the Ki-67 level might assist in the diagnosis of AIS in patients with T2DM.

Endoscopic retrograde cholangiopancreatography,endoscopic papillary balloon dilation,and laparoscopic hepatectomy for intraand extrahepatic bile duct stones

BACKGROUND Intrahepatic and extrahepatic bile duct stones(BDSs)have a high rate of residual stones,a high risk of recurrence,and a high rate of reoperation.It is very important to take timely and effective surgical intervention for patients.AIM To analyze the efficacy,postoperative rehabilitation,and quality of life(QoL)of patients with intra-and extrahepatic BDSs treated with endoscopic retrograde cholangiopancreatography(ERCP)+endoscopic papillary balloon dilation(EPBD)+laparoscopic hepatectomy(LH).METHODS This study selected 114 cases of intra-and extrahepatic BDSs from April 2021 to April 2024,consisting of 55 cases in the control group receiving laparoscopic common bile duct exploration and LH and 59 cases in the observation group treated with ERCP+EPBD+LH.Efficacy,surgical indicators[operation time(OT)and intraoperative blood loss(IBL)],postoperative rehabilitation(time for body temperature to return to normal,time for pain relief,and time for drainage to reduce jaundice),hospital stay,medical expenses,and QoL[Gastrointestinal Quality of Life Index(GIQLI)]were comparatively analyzed.Further,Logistic regression analysis was conducted to analyze factors influencing the QoL of patients with intra-and extrahepatic BDSs.RESULTS The data demonstrated a higher overall effective rate in the observation group compared to the control group(P=0.011),together with notably reduced OT,less IBL,shorter body temperature recovery time,pain relief time,time for drainage to reduce jaundice,and hospital stay(all P<0.05).The postoperative GIQLI of the observation group was more significantly increased compared to the control group(P<0.05).The two groups demonstrated no marked difference in medical expenses(P>0.05).CONCLUSION The above indicates that ERCP+EPBD+LH is effective in treating patients with intra-and extrahepatic BDSs,which is conducive to postoperative rehabilitation and QoL improvement,with promising prospects for clinical promotion.

Unveiling the clinicopathological enigma of crawling-type gastric adenocarcinoma

In this editorial we comment on the article by Xu et al.Gastric adenocarcinoma(GA)is a malignancy which arises from the gastric mucosa and encompasses heterogenous tumors with varying characteristics.There are two main classifications:Lauren’s and the World Health Organization distinguishing the diverse types of GA depending on clinical,genetic,morphological and epidemiological features.“Crawling-type”adenocarcinoma(CRA)is a subtype characterized by irregularly fused glands with low-grade cellular atypia.Moreover,CRA represents differentiated tumor cells resembling intestinal metaplasia which results in misdiagnosis.The diagnosis is of utmost importance,as well as the subclassification and thorough pathological assessment.With regard to the symptoms of GA,these depend on the stage of the disease.Diagnostic methods play a crucial role in assessing the extent of the tumor and the stage of the disease.Nevertheless,early detection of CRA remains challenging due to its histological features.In summary,CRA is a distinct type of GA with particular clinicopathological and histological characteristics.Despite its significance,it not distinguished as a subtype,resulting in diagnostic challenges.Diagnosis is based on careful observation and thorough biopsy analysis,indicating the importance of comprehensive pathological assessment.

Hepatoid adenocarcinoma of the lung:A case report

BACKGROUND Hepatoid adenocarcinoma of the lung(HAL)is a rare type of non-small cell lung cancer(NSCLC),histologically similar to hepatocellular carcinoma.HAL has high malignancy and poor prognosis,and a better treatment plan needs further study.CASE SUMMARY In order to deeply understand the occurrence and development of HAL,here we report a case of HAL with extensive metastasis of alpha fetoprotein negative KRAS A146T mutation.The patient refused chemotherapy and received one course of treatment(immune checkpoint inhibitors),and died three months later due to progressive disease.CONCLUSION HAL is a special type of NSCLC.The surgical treatment of HAL in the limited stage can achieve long-term survival,but most of them were in the advanced stage when they were found,and the prognosis was poor,which requires multidisciplinary comprehensive treatment.

Vaginal clear cell adenocarcinoma in Herlyn-Werner-Wunderlich syndrome:A case report

BACKGROUND Herlyn-Werner-Wunderlich(HWW)syndrome is a rare Müllerian duct anomaly,characterized by a combination of urogenital abnormalities.The occurrence of primary cervico-vaginal carcinomas in patients with HWW syndrome is excep-tionally rare,posing significant challenges for screening,early diagnosis,and effective management.CASE SUMMARY We report a rare case of primary clear cell carcinoma of the vagina complicated in a 40-year-old woman with HWW syndrome.The patient presented with irregular vaginal bleeding for 4 years.On gynecological examination,an oblique vaginal septum was suspected.Surgical resection of the vaginal septum revealed a com-municating fistula and a tumor on the left vagina and the left side of the septum,which was confirmed as clear cell carcinoma.One month later,she underwent a radical hysterectomy,vaginectomy,bilateral salpingo-oophorectomy,and pelvic lymph node dissection.Due to significant side effects,she completed only one course of chemotherapy.A year later,lung metastasis was detected and continued to grow.A thoracoscopic wedge resection of the right upper lobe was performed 4 years after the initial surgery.We also conducted a systemic review of the lite-rature on primary cervical or vaginal carcinoma in HWW syndrome to explore this rare entity.CONCLUSION Cervico-vaginal adenocarcinomas in patients with HWW syndrome are occult,and require early surgical intervention and regular imaging surveillance.

Prognostic significance of grade of malignancy based on histopathological differentiation and Ki-67 in pancreatic ductal adenocarcinoma

Objective:Tumor cell malignancy is indicated by histopathological differentiation and cell proliferation.Ki-67,an indicator of cellular proliferation,has been used for tumor grading and classification in breast cancer and neuroendocrine tumors.However,its prognostic significance in pancreatic ductal adenocarcinoma(PDAC)remains uncertain.Methods:Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled,and relevant prognostic factors were examined.Grade of malignancy(GOM),a novel index based on histopathological differentiation and Ki-67,is proposed,and its clinical significance was evaluated.Results:The optimal threshold for Ki-67 was determined to be 30%.Patients with a Ki-67 expression level>30%rather than≤30%had significantly shorter 5-year overall survival(OS)and recurrence-free survival(RFS).In multivariate analysis,both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and RFS.The GOM was used to independently stratify OS and RFS into 3 tiers,regardless of TNM stage and other established prognostic factors.The tumor-nodemetastasis-GOM stage was used to stratify survival into 5 distinct tiers,and surpassed the predictive performance of TNM stage for OS and RFS.Conclusions:Ki-67 is a valuable prognostic indicator for PDAC.Inclusion of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.

Clinical pathological characteristics of“crawling-type”gastric adenocarcinoma cancer:A case report

BACKGROUND Gastric cancer(GC)is a significant health problem worldwide,and early detection and accurate diagnosis are crucial for improving patient outcomes.Crawling-type gastric adenocarcinoma is a rare subtype of GC that has unique histopathological and clinical characteristics,and its diagnosis and management can be challenging.This pathological type of GC is also rare.CASE SUMMARY Here,we report the case of a patient who underwent ordinary endoscopy,na-rrow-band imaging,and endoscopic ultrasonography intending to determine the extent of tumor invasion and upper abdominal enhanced computed tomography and whether there was tumor metastasis.Then,endoscopic submucosal dissection was performed.After pathological and immunohistochemical examination,the pathological diagnosis was crawling-type gastric adenocarcinoma.This is a very rare and special pathological type of tumor.This case highlights the importance of using advanced endoscopic techniques and pathological examination in diagnosing and managing gastric crawling-type adenocarcinoma.Moreover,the findings underscore the need for continued research and clinical experience in this rare subtype of GC to improve patient outcomes.CONCLUSION The“crawling-type”GC is a rare and specific tumor pathology.It is difficult to identify and diagnose gliomas via endoscopy.The tumor is ill-defined,with a flat appearance and indistinct borders due to the lack of contrast against the background mucosa.Pathology revealed that the tumor cells were hand-like,so the patient has diagnosed with“crawling-type”gastric adenocarcinoma.

Leveraging diverse cell-death patterns to predict the clinical outcome of immune checkpoint therapy in lung adenocarcinoma:Based on muti-omics analysis and vitro assay

Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.