{"title":"<i>SOX11</i> as a potential prognostic biomarker in hepatocellular carcinoma linked to immune infiltration and ferroptosis.","authors":"Hongyu Chen, Qiangguo Ao, Yueling Wang, Yue Qian, Qingli Cheng, Wei Zhang","doi":"10.21147/j.issn.1000-9604.2024.04.03","DOIUrl":"10.21147/j.issn.1000-9604.2024.04.03","url":null,"abstract":"<p><strong>Objective: </strong><i>SOX11</i> is expressed in numerous malignancies, including hepatocellular carcinomas (HCC), but its oncogenic function has not been elucidated. Here, we performed a comprehensive bioinformatics analysis of the Liver Hepatocellular Carcinoma (LIHC) dataset to investigate the function of <i>SOX11</i> in tumorgenesis.</p><p><strong>Methods: </strong><i>SOX11</i> expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were validated by immunohistochemistry (IHC). Co-expression, differential expression, and functional analyses utilized TCGA-LIHC, Timer 2.0, Metascape, GTEx, and LinkedOmics databases. Associations with immune infiltration, ferroptosis, and immune checkpoint genes were assessed. Genetic changes were explored via CBioPortal. Logistic regression, receiver operating characteristic curve (ROC), Kaplan-Meier analysis, and nomogram modeling evaluated associations with HCC clinicopathological features. <i>SOX11</i>'s impact on proliferation and migration was studied in HepG2 and HuH7 cell lines.</p><p><strong>Results: </strong><i>SOX11</i> was significantly elevated in HCC tumors compared to controls. <i>SOX11</i>-associated genes exhibited differential expression in pathways involving extracellular membrane ion channels. Significant associations were found between <i>SOX11</i> levels, immune infiltration, ferroptosis, and immune checkpoint genes in HCC tissue. <i>SOX11</i> levels correlated with HCC stage, histologic grade, and tumor status, and independently predicted overall and disease-specific survival. <i>SOX11</i> expression effectively distinguished between tumor and normal liver tissue. Spearman correlations highlighted a significant relationship between <i>SOX11</i> and ferroptosis-associated genes. Decreased <i>SOX11</i> levels in HepG2 and HuH7 cells resulted in reduced proliferation and migration.</p><p><strong>Conclusions: </strong><i>SOX11</i> was found to represent a promising biomarker within HCC diagnosis and prognosis together with being a possible drug-target.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 4","pages":"378-397"},"PeriodicalIF":7.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ji Yeong An, Sung Eun Oh, Soomin Ahn, Hyoung-Ii Kim, Yoo Min Kim, Minah Cho, Keun Won Ryu, Hong Man Yoon, Young Kyu Park, In Gyu Kwon, Sung Hoon Noh, Kyung Hee Lee, In Cho, Myoung Won Son, Jong Won Kim, Young-Woo Kim
{"title":"A pilot clinical study to evaluate feasibility of using single patient classifier as a prognostic test in stage II<b>-</b>III gastric cancer patients.","authors":"Ji Yeong An, Sung Eun Oh, Soomin Ahn, Hyoung-Ii Kim, Yoo Min Kim, Minah Cho, Keun Won Ryu, Hong Man Yoon, Young Kyu Park, In Gyu Kwon, Sung Hoon Noh, Kyung Hee Lee, In Cho, Myoung Won Son, Jong Won Kim, Young-Woo Kim","doi":"10.21147/j.issn.1000-9604.2024.04.02","DOIUrl":"10.21147/j.issn.1000-9604.2024.04.02","url":null,"abstract":"<p><strong>Objective: </strong>Precision medicine approaches emphasize the importance of reliable prognostic tools for guiding individualized therapy decisions. In this study, we evaluated the clinical feasibility of the single patient classifier (SPC) test, a new clinical-grade prognostic assay, in stage II-III gastric cancer patients.</p><p><strong>Methods: </strong>A prospective multicenter study was conducted, involving 237 patients who underwent gastrectomy between September 2019 and August 2020 across nine hospitals. The SPC test was employed to stratify patients into risk groups, and its feasibility and performance were evaluated. The primary endpoint was the proportion of the cases in which the test results were timely delivered before selecting postoperative treatment. Furthermore, 3-year disease-free survivals of risk groups were analyzed.</p><p><strong>Results: </strong>The SPC test met the primary endpoint criteria. The 99.5% of SPC tests were timely delivered to hospitals before the postoperative treatment started. In a clinical setting, the median time from the specimen transfer to laboratory to the result delivery to hospital was 4 d. Furthermore, 3-year disease-free survivals were significantly different between risk groups classified with SPC tests.</p><p><strong>Conclusions: </strong>This study highlights the SPC test's feasibility in offering crucial information timely delivered for making informed decisions regarding postoperative treatment strategies. It also provides evidence to support the implementation of a future prospective clinical trial aimed at evaluating the clinical utility of the SPC test in guiding personalized treatment decisions for gastric cancer patients.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 4","pages":"368-377"},"PeriodicalIF":7.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nan Chen, Minghe Zhao, Yunfeng Yao, Lin Wang, Yifan Peng, Tingting Sun, Tiancheng Zhan, Jun Zhao, Aiwen Wu
{"title":"Neoadjuvant chemotherapy with capecitabine combined with oxaliplatin for mid-low locally advanced rectal cancer with negative mesorectal fascia: Long-term outcomes of a prospective trial (PKUCH-R03 trial).","authors":"Nan Chen, Minghe Zhao, Yunfeng Yao, Lin Wang, Yifan Peng, Tingting Sun, Tiancheng Zhan, Jun Zhao, Aiwen Wu","doi":"10.21147/j.issn.1000-9604.2024.04.05","DOIUrl":"10.21147/j.issn.1000-9604.2024.04.05","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the safety and efficacy of neoadjuvant chemotherapy (NCT) in mid-low locally advanced rectal cancer with negative mesorectal fascia (MRF).</p><p><strong>Methods: </strong>This prospective, single-arm phase II trial was designed and conducted at Peking University Cancer Hospital. The patients who provided consent received 3 months of NCT (capecitabine and oxaliplatin, CapOX) followed by total mesorectal excision (TME). The primary endpoint was the rate of pathological complete response (pCR).</p><p><strong>Results: </strong>From January 2019 through December 2021, a total of 53 patients were enrolled, 7.5% of whom experienced grade 3-4 adverse events during NCT. The pCR rate was 17.0% for the entire cohort, and the overall rate of postoperative complications was 37.7% (1.9% of grade IIIa patients). The 3-year disease-free survival rate was 91.4%, and 23.5% (12/51) of the patients suffered from major low anterior resection syndrome (LARS). Postoperative complications were independently associated with major LARS.</p><p><strong>Conclusions: </strong>For patients with mid-low rectal cancer with negative MRF, 3 months of NCT were found to yield a favorable tumor response with acceptable toxicity. With fair long-term survival, the NCT regimen could be associated with low rates of perioperative complications as well as acceptable anal function.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 4","pages":"410-420"},"PeriodicalIF":7.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142157160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Potential value of detection of minimal residual disease in colorectal cancer following radical resection.","authors":"Wenji Pu, Fang Chen, Yuan Tang, Yanling Qu, Yunzhu Han, Jiandong Zha, Jing Jin, Fengming Kong","doi":"10.21147/j.issn.1000-9604.2024.04.07","DOIUrl":"10.21147/j.issn.1000-9604.2024.04.07","url":null,"abstract":"<p><p>Although there has been significant advancement in the identification and management of colorectal cancer (CRC) in recent years, there is still room for improvement in the current standard treatment regimen. One area of concern is the lack of reliable tumor markers to predict treatment efficacy and guide tailored care. Due to its dynamic, effective, and non-invasive benefits over tissue biopsy, the detection of minimal or molecular residual lesions (MRD) based on circulating tumor DNA (ctDNA) is beneficial to the clinical development of drugs for patients with CRC after radical treatment, as well as for continuous monitoring of tumor recurrence and malignancy molecular gene evolution. The detection of ctDNA can currently be used to guide individual postoperative auxiliary treatment decisions (upgrade or downgrade treatment) in CRC, stratify the risk of clinical recurrence more precisely, and predict the risk of recurrence in advance of imaging examination, according to a large number of observational or prospective clinical studies. With increasing clarity comes the possibility of selecting a regimen of treatment based on postoperative ctDNA, which also improves the accuracy of clinical recurrence risk assessment for CRC. Therefore, it is anticipated that the identification of ctDNA would alter the current framework for dealing with CRC and lead to individualized, stratified precision therapy; however, additional confirmation will require subsequent high-quality, prospective, large-scale randomized controlled studies. This article will provide an overview of the definition and clinical significance of MRD, the primary indications and technological challenges for MRD detection, along with the advancement in clinical research about ctDNA detection following radical resection of the CRC.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 4","pages":"442-454"},"PeriodicalIF":7.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immune status and combined immunotherapy progression in Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant tumors.","authors":"Dongsheng He, Rilan Bai, Naifei Chen, Jiuwei Cui","doi":"10.21147/j.issn.1000-9604.2024.04.06","DOIUrl":"10.21147/j.issn.1000-9604.2024.04.06","url":null,"abstract":"<p><p>Kirsten rat sarcoma viral oncogene homolog (<i>KRAS</i>) is the most frequently mutated oncogene, occurring in various tumor types. Despite extensive efforts over the past 40 years to develop inhibitors targeting KRAS mutations, resistance to these inhibitors has eventually emerged. A more precise understanding of KRAS mutations and the mechanism of resistance development is essential for creating novel inhibitors that target specifically KRAS mutations and can delay or overcome resistance. Immunotherapy has developed rapidly in recent years, and in-depth dissection of the tumor immune microenvironment has led researchers to shift their focus to patients with KRAS mutations, finding that immune factors play an essential role in KRAS-mutant (KRAS-Mut) tumor therapy and targeted drug resistance. Breakthroughs and transitions from targeted therapy to immunotherapy have provided new hope for treating refractory patients. Here, we reviewed KRAS mutation-targeted treatment strategies and resistance issues, focusing on our in-depth exploration of the specific immune status of patients with KRAS mutations and the impact of body immunity following KRAS inhibition. We aimed to guide innovative approaches combining RAS inhibition with immunotherapy, review advances in preclinical and clinical stages, and discuss challenges and future directions.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 4","pages":"421-441"},"PeriodicalIF":7.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tumor-derived DEFB1 induces immune tolerance by inhibiting maturation of dendritic cell and impairing CD8+ T cell function in esophageal squamous cell carcinoma.","authors":"Jingjing Duan, Haotian Wang, Minglu Liu, Yin Chen, Ning Li, Jieqiong Liu, Lingxiong Wang, Lin Li, Yaru Liu, Pengfei Dong, Xiuxuan Wang, Zhongyi Fan, Shunchang Jiao","doi":"10.21147/j.issn.1000-9604.2024.04.01","DOIUrl":"10.21147/j.issn.1000-9604.2024.04.01","url":null,"abstract":"<p><strong>Objective: </strong>CD8+ T cells are the key effector cells in the anti-tumor immune response. The mechanism underlying the infiltration of CD8+ T cells in esophageal squamous cell carcinoma (ESCC) has not been clearly elucidated.</p><p><strong>Methods: </strong>Fresh ESCC tissues were collected and grouped according to the infiltration density of CD8+ T cells. After the transcriptome sequencing on these samples and the combined analyses with The Cancer Genome Atlas (TCGA) ESCC data, a secreted protein DEFB1 was selected to explore its potential role in the infiltration of CD8+ T cells. Bioinformatics analyses, histological verification and <i>in vitro</i> experiments were then performed.</p><p><strong>Results: </strong>DEFB1 was highly expressed in ESCC, and the high expression of DEFB1 was an independent risk factor for overall survival. Since the up-regulation or down-regulation of DEFB1 did not affect the proliferation, migration and apoptosis of ESCC cells, we speculated that the oncogenic effect of DEFB1 was achieved by regulating microenvironmental characteristics. Bioinformatics analyses suggested that DEFB1 might play a major role in the inflammatory response and anti-tumor immune response, and correlate to the infiltration of immature dendritic cell (imDC) in ESCC. Histological analyses further confirmed that there were less CD8+ T cells infiltrated, less CD83+ mature DC (mDC) infiltrated and more CD1a+ imDC infiltrated in those ESCC samples with high expression of DEFB1. After the treatment with recombinant DEFB1 protein, the maturation of DC was hindered significantly, followed by the impairment of the killing effects of T cells in both 2D and 3D culture <i>in vitro</i>.</p><p><strong>Conclusions: </strong>Tumor-derived DEFB1 can inhibit the maturation of DC and weaken the function of CD8+ T cells, accounting for the immune tolerance in ESCC. The role of DEFB1 in ESCC deserves further exploration.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 4","pages":"351-367"},"PeriodicalIF":7.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CSCO guidelines for colorectal cancer version 2024: Updates and discussions.","authors":"Liubo Chen, Hanguang Hu, Ying Yuan, Shanshan Weng","doi":"10.21147/j.issn.1000-9604.2024.03.01","DOIUrl":"10.21147/j.issn.1000-9604.2024.03.01","url":null,"abstract":"","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 3","pages":"233-239"},"PeriodicalIF":7.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11230882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer.","authors":"Zhifei Li, Huan Zhao, Huihui Hu, Haili Shang, Yongjing Ren, Wenhui Qiu, Hao Su, Huifang Lyu, Xiaobing Chen","doi":"10.21147/j.issn.1000-9604.2024.03.07","DOIUrl":"10.21147/j.issn.1000-9604.2024.03.07","url":null,"abstract":"<p><p>Gastric cancer is one of the most prevalent cancers worldwide, and human epidermal growth factor receptor 2 (HER2)-positive cases account for approximately 20% of the total cases. Currently, trastuzumab + chemotherapy is the recommended first-line treatment for patients with HER2-positive advanced gastric cancer, and the combination has exhibited definite efficacy in HER2-targeted therapy. However, the emergence of drug resistance during treatment considerably reduces its effectiveness; thus, it is imperative to investigate the potential mechanisms underlying resistance. In the present review article, we comprehensively introduce multiple mechanisms underlying resistance to trastuzumab in HER2-positive gastric cancer cases, aiming to provide insights for rectifying issues associated with resistance to trastuzumab and devising subsequent treatment strategies.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 3","pages":"306-321"},"PeriodicalIF":7.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11230884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dechao Feng, Yuhan Xiao, Jie Wang, Ruicheng Wu, Zhouting Tuo, Koo Han Yoo, Wuran Wei, Dilinaer Wusiman, Zhipeng Wang, Dengxiong Li, Yubo Yang, William C Cho, Mang Ke
{"title":"Unraveling links between aging, circadian rhythm and cancer: Insights from evidence-based analysis.","authors":"Dechao Feng, Yuhan Xiao, Jie Wang, Ruicheng Wu, Zhouting Tuo, Koo Han Yoo, Wuran Wei, Dilinaer Wusiman, Zhipeng Wang, Dengxiong Li, Yubo Yang, William C Cho, Mang Ke","doi":"10.21147/j.issn.1000-9604.2024.03.09","DOIUrl":"10.21147/j.issn.1000-9604.2024.03.09","url":null,"abstract":"<p><p>Aging and circadian rhythms have been connected for decades, but their molecular interaction has remained unknown, especially for cancers. In this situation, we summarized the current research actuality and problems in this field using the bibliometric analysis. Publications in the PubMed and Web of Science databases were retrieved. Overall, there is a rising trend in the publication volume regarding aging and circadian rhythms in the field of cancer. Researchers from USA, Germany, Italy, China and England have greater studies than others. Top three publication institutions are University of California System, UDICE-French Research Universities and University of Texas System. Current research hotspots include oxidative stress, breast cancer, melatonin, cell cycle, calorie restriction, prostate cancer and NF-KB. In conclusion, results generated by bibliometric analysis indicate that many approaches involve in the complex interactions between aging and circadian rhythm in cancer. These established and emerging research directions guide our exploration of the regulatory mechanisms of aging and circadian rhythms in cancer and provide a reference for developing new research avenues.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 3","pages":"341-350"},"PeriodicalIF":7.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11230883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yifei Wang, Yidan Ma, Lei He, Jun Du, Xiaoguang Li, Peng Jiao, Xiaonan Wu, Xiaomao Xu, Wei Zhou, Li Yang, Jing Di, Changbin Zhu, Liming Xu, Tianlin Sun, Lin Li, Dongge Liu, Zheng Wang
{"title":"Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population: An integrated genomic and transcriptional analysis.","authors":"Yifei Wang, Yidan Ma, Lei He, Jun Du, Xiaoguang Li, Peng Jiao, Xiaonan Wu, Xiaomao Xu, Wei Zhou, Li Yang, Jing Di, Changbin Zhu, Liming Xu, Tianlin Sun, Lin Li, Dongge Liu, Zheng Wang","doi":"10.21147/j.issn.1000-9604.2024.03.05","DOIUrl":"10.21147/j.issn.1000-9604.2024.03.05","url":null,"abstract":"<p><strong>Objective: </strong>The clinical significance of homologous recombination deficiency (HRD) in breast cancer, ovarian cancer, and prostate cancer has been established, but the value of HRD in non-small cell lung cancer (NSCLC) has not been fully investigated. This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.</p><p><strong>Methods: </strong>A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled. HRD status was assessed using the AmoyDx Genomic Scar Score (GSS), with a score of ≥50 considered HRD-positive. Genomic, transcriptomic, tumor microenvironmental characteristics and prognosis between HRD-positive and HRD-negative patients were analyzed.</p><p><strong>Results: </strong>Of the patients, 25.1% (89/355) were HRD-positive. Compared to HRD-negative patients, HRD-positive patients had more somatic pathogenic homologous recombination repair (HRR) mutations, higher tumor mutation burden (TMB) (P<0.001), and fewer driver gene mutations (P<0.001). Furthermore, HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes, <i>MET</i> and <i>MYC</i> in epidermal growth factor receptor (<i>EGFR</i>)<i>/</i>anaplastic lymphoma kinase (<i>ALK</i>) mutant NSCLC, and more <i>PIK3CA</i> and <i>AURKA</i> in <i>EGFR/ALK</i> wild-type NSCLC. HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity. HRD-negative NSCLC showed activated signatures of major histocompatibility complex (MHC)-II, interferon (IFN)-γ and effector memory CD8+ T cells. HRD-positive patients had a worse prognosis and shorter progression-free survival (PFS) to targeted therapy (first- and third-generation EGFR-TKIs) (P=0.042). Additionally, HRD-positive, <i>EGFR/ALK</i> wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.</p><p><strong>Conclusions: </strong>Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC. Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC. This study highlights potential actionable alterations in HRD-positive NSCLC, suggesting possible combinational therapeutic strategies for these patients.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 3","pages":"282-297"},"PeriodicalIF":7.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11230889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}