Development and validation of a five-gene model to predict postoperative brain metastasis in operable lung adenocarcinoma.

One of the most common sites of extra-thoracic distant metastasis of nonsmall-cell lung cancer is the brain. Our study was performed to discover genes associated with postoperative brain metastasis in operable lung adenocarcinoma (LUAD). RNA seq was performed in specimens of primary LUAD from seven patients with brain metastases and 45 patients without recurrence. Immunohistochemical (IHC) assays of the differentially expressed genes were conducted in 272 surgical-resected LUAD specimens. LASSO Cox regression was used to filter genes related to brain metastasis and construct brain metastasis score (BMS). GSE31210 and GSE50081 were used as validation datasets of the model. Gene Set Enrichment Analysis was performed in patients stratified by risk of brain metastasis in the TCGA database. Through the initial screening, eight genes (CDK1, KPNA2, KIF11, ASPM, CEP55, HJURP, TYMS and TTK) were selected for IHC analyses. The BMS based on protein expression levels of five genes (TYMS, CDK1, HJURP, CEP55 and KIF11) was highly predictive of brain metastasis in our cohort (12-month AUC: 0.791, 36-month AUC: 0.766, 60-month AUC: 0.812). The validation of BMS on overall survival of GSE31210 and GSE50081 also showed excellent predictive value (GSE31210, 12-month AUC: 0.682, 36-month AUC: 0.713, 60-month AUC: 0.762; GSE50081, 12-month AUC: 0.706, 36-month AUC: 0.700, 60-month AUC: 0.724). Further analyses showed high BMS was associated with pathways of cell cycle and DNA repair. A five-gene predictive model exhibits potential clinical utility for the prediction of postoperative brain metastasis and the individual management of patients with LUAD after radical resection.

Residual tumor descriptors proposed by the International Association for the Study of Lung Cancer may not be applicable to stage I and ground-glass opacity-featured non-small cell lung cancer.

Background: The International Association for the Study of Lung Cancer (IASLC) has proposed a residual tumor descriptor, essential for subsequent treatments. This study aimed to validate the prognostic effect of the proposed R descriptor and restrict its scope of clinical application in a large-scale cohort with non-small cell lung cancer (NSCLC). Methods: Patients, who underwent lobectomy from January 2010 to May 2019, were retrospectively reviewed. Patients were categorized according to the different R classification standards proposed by Union for International Cancer Control (UICC) and IASLC. Results: Among 5,200 enrolled patients with NSCLC, 1,727 and 9 cases of UICC-R0 were re-evaluated as uncertain resection [R(un)] and R1, respectively. After reclassification, there were 3,228 (62.1%) cases of R0, 1,727 (33.2%) cases of R(un), 151 (2.9%) cases of R1, and 94 (1.8%) cases of R2. Not performing rigorous systematic nodal dissection (SND) or lobe-specific SND (68.3%) was the main reason for the alteration from R0 to R(un). Patients with R(un) showed intermediate survival between those with R0 and R1. Further multivariable Cox analysis indicated that the proposed R descriptor was an independent prognostic factor for overall survival (OS) and recurrence-free survival (RFS). However, subgroup analysis of OS and RFS revealed that there was no significant difference between R0 and R(un) in patients with ground-glass opacity (GGO) or patients with tumor-node-metastasis stage I. Conclusions: R(un) represented an intermediate type between R0 and R1. Our study provided an external validation for new residual tumor descriptors for NSCLC proposed by IASLC. Proposed residual tumor descriptors were applicable in radiologic solid NSCLC and stage II-III NSCLC, but were ineffective for GGO-featured or stage I NSCLC.

Characterization of immune microenvironment infiltration and m6A regulator-mediated RNA methylation modification patterns in osteoarthritis.

Background: Few studies have been reported the potential role of N6-methyladenosine (m6A) modification in osteoarthritis (OA). We investigated the patterns of m6A modification in the immune microenvironment of OA. Methods: We evaluated the m6A modification patterns based on 22 m6A regulators in 139 OA samples and systematically associated these modification patterns with immune cell infiltration characteristics. The function of m6A phenotype-related differentially expressed genes (DEGs) was investigated using gene enrichment analysis. An m6A score model was constructed using principal component analysis (PCA), and an OA prediction model was established based on the key m6A regulators. We used real-time PCR analysis to detect the changes of gene expression in the cell model of OA. Results: Healthy and OA samples showed significant differences in the expression of m6A regulators. Nine key m6A regulators, two m6A modification patterns, m6A-related genes and two gene clusters were identified. Some m6A regulators had a strong correlation with each other. Gene clusters and m6A clusters have high similarity, and cluster A corresponds to a high m6A score. Immunocytes infiltration differed significantly between the two clusters, with the m6A cluster B and gene cluster B having more types of infiltrating immunocytes than cluster A. The predictive model can also predict the progression of OA through m6A regulators expression. The results of real-time PCR analysis showed that the gene expression in the cell model of OA is similar to that of the m6A cluster B. Conclusions: Our study reveals for the first time the potential regulatory mechanism of m6A modification in the immune microenvironment of OA. This study also sheds new light on the pathogenesis of OA.

Clinical, pathological and radiologic features of minute pulmonary meningothelial-like nodules.

OBJECTIVES: Reports about the radiologic features of minute pulmonary meningothelial-like nodules are sparse. This study aims to investigate the radiologic features of minute pulmonary meningothelial-like nodules. METHOD: From January 2016 to April 2019, 7589 patients underwent pulmonary resections at Fudan University Shanghai Cancer Center. Postoperative pathology records were reviewed retrospectively. Fifty-nine patients with minute pulmonary meningothelial-like nodule were included. The identification of minute pulmonary meningothelial-like nodules in pathology specimen included pathologically confirmed in resected nodules, and discovery in the peripheral tissue of other resected nodules incidentally. We went back and checked all the pre-operative scans of patients to analyze surgical decision and observe any change of visible minute pulmonary meningothelial-like nodule over time. Clinic, radiologic and pathological features were collected. RESULT: Fifty-nine patients included 10 men and 49 women, with a mean age of 57.7. Five patients had history, while 54 patients were non-smokers. 79 min pulmonary meningothelial-like nodules was found. Of them, 36 nodules were not visible on computed tomography scan. 43 nodules were visible on computed tomography scan, with an average size of 5.3 mm in 29 patients. Computed tomography appearance included pure ground-glass opacity in 36, mixed in 2, and solid nodules in 5. Nearly half of patients had a pre-operative follow-up more than 6 months (13/29, 44.8%). The median pre-operative radiologic follow-up was 4.9 months. Approximately 90% of patients underwent pulmonary surgery because of other malignant nodule on chest computed tomography scan (52/59, 88.1%). CONCLUSION: Most minute pulmonary meningothelial-like nodules tend to present as ground-glass opacity, especially pure ground-glass opacity. Continuous computed tomography monitoring revealed no radiologic change over time. Continuous computed tomography monitoring was necessary part of management of minute pulmonary meningothelial-like nodule.

Subsolid Lesions Exceeding 3 Centimeters: The Ground-Glass Opacity Component Still Matters.

BACKGROUND: Recent studies on the favorable prognosis of ground-glass opacities (GGO) featured lung adenocarcinoma compared with solid nodules were limited to small tumors measuring 3.0 cm or less. This study investigated whether the GGO component could predict better prognosis in patients with large subsolid lesions exceeding 3 cm compared with small solid nodules within the same clinical T category. METHODS: From 2010 to 2015, 1010 patients with completely resected clinical N0 lung adenocarcinoma were enrolled, including 860 solid lesions and 150 subsolid lesions exceeding 3 cm. To analyze the prognostic significance of the GGO component, propensity score matching adjusting the solid component size was performed. RESULTS: After propensity score matching, 144 pairs of patients were analyzed. The mean size of the solid component was 23.7 mm in the GGO group and 24.4 mm in the solid group (P = .450). The GGO group had significantly better overall survival (P = .011) and recurrence-free survival (P = .003), which were also validated in patients with solid-predominant lesions. Subgroup analysis showed the GGO group was associated with better prognosis in each clinical T category. CONCLUSIONS: The prognosis of patients with GGO lesions exceeding 3 cm was better than that of patients with small solid lesions, even within the same clinical T category. Clinical T classification incorporating the GGO component may provide better prognostic prediction for patients with lung cancer exceeding 3 cm.

Primary Tumor Resection Improves Survival for EGFR-TKI-Treated Patients With Occult M1a Lung Adenocarcinoma.

BACKGROUND: The role of primary tumor resection in occult M1a lung adenocarcinoma remains unclear, especially for patients receiving targeted therapy. The purpose of this study is to assess the effect of primary tumor resection on overall survival (OS) in lung adenocarcinoma patients with occult pleural disseminations receiving targeted therapy. METHODS: Lung adenocarcinoma patients with intraoperatively-confirmed occult pleural dissemination (M1a), who hospitalized in the Department of Thoracic Surgery in Fudan Shanghai Cancer Center from May 2008 to December 2017 and received EGFR-TKIs therapy, were enrolled. Log-rank tests were used to compare the survival differences between groups. RESULTS: 34 patients receiving EGFR-TKIs were enrolled. The majority of them were never smokers (29/34, 85.3%). Among the enrolled patients, 20 (58.8%) patients underwent primary tumor resection, while 14 (41.2%) patients not. There was no distributional difference of baselines between patients undergoing and not undergoing primary tumor resection. Further analyses demonstrated that the patients undergoing primary tumor resection had a prolonged OS compared with those not (log-rank P= 0.042). The 2-year and 5-year OS for patients receiving primary tumor resection and EGFR-TKIs was 90.0% and 60.1%. CONCLUSIONS: Primary tumor resection was associated with improved survival in patients with occult intraoperatively-confirmed M1a adenocarcinoma receiving EGFR-TKIs.

Silencing of miR-483-5p alleviates postmenopausal osteoporosis by targeting SATB2 and PI3K/AKT pathway.

Postmenopausal osteoporosis (PMOP) poses a significant threat to women's health worldwide. However, detailed molecular mechanism and therapeutic strategy for PMOP remain insufficient. Accumulating evidence suggests that miR-48-5p is implicated in the pathogenesis of osteoporosis. The present study aimed to determine the role and mechanism of miR-483-5p in PMOP. Results from PMOP patients demonstrated that miR-483-5p was up-regulated and SATB2 was down-regulated. Luciferase reporter assay identified SATB2 as a direct target gene of miR-483-5p. Experiments in MC3T3-E1 cells indicated that miR-483-5p mimic markedly inhibited cell viability as well as the expressions of OPG, RUNX2 and BMP2. And miR-483-5p inhibitor, SATB2-overexpressed lentiviruses (Lv-SATB2) or LY294002 (PI3K/AKT inhibitor) significantly reversed the above results. Similarly, PI3K/AKT signaling was activated by miR-483-5p mimic, and was inhibited in miR-483-5p inhibitor, Lv-SATB2 or LY294002 treated cells. In vivo experiments showed that miR-483-5p inhibitor significantly increased the bone mineral density and biomechanical parameters of femurs in ovariectomized (OVX) rats by targeting SATB2. In addition, the osteogenic differentiation and PI3K/AKT signaling were also regulated by miR-483-5p-SATB2 axis. Taken together, our findings indicated that miR-483-5p contributed to the pathogenesis of PMOP by inhibiting SATB2 and activating PI3K/AKT pathway. MiR-483-5p/SATB2 could be selected as a potential therapeutic target for PMOP.

Excellent Prognosis of Patients With Invasive Lung Adenocarcinomas During Surgery Misdiagnosed as Atypical Adenomatous Hyperplasia, Adenocarcinoma In Situ, or Minimally Invasive Adenocarcinoma by Frozen Section.

BACKGROUND: Our previous study revealed that intraoperative frozen section (FS) analysis could differentiate invasive lung adenocarcinoma (LUAD) accurately from preinvasive lesions. However, few articles have analyzed the clinical impact of FS errors such as underestimation of invasive adenocarcinomas (IACs), and whether complementary therapy is needed remains controversial. RESEARCH QUESTION: What is the prognosis of patients undergoing limited resection for invasive LUAD misdiagnosed as atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), or minimally invasive adenocarcinoma (MIA) by intraoperative FS analysis? STUDY DESIGN AND METHODS: From 2012 through 2018, data on 3031 patients undergoing sublobar resection of AAH, AIS, or MIA diagnosed by FS analysis were collected. The concordance rate between FS analysis and final pathologic results was evaluated. To assess the clinical significance of a discrepancy between FS and final pathologic results, patients with final pathologic results of IAC were identified for prognostic evaluation. RESULTS: When AAH, AIS, and MIA were classified together as a group, the overall concordance rate between FS and final pathologic results was 93.7%, and 192 patients (6.3%) received an upgraded diagnosis from the final pathologic results. Misdiagnosed IACs consisted of 94 patients (48.9%) with lepidic-predominant adenocarcinoma, 77 patients (40.1%) with acinar predominant adenocarcinoma, 19 patients (9.9%) with papillary predominant adenocarcinoma, one patient with solid predominant adenocarcinoma, and one patient with invasive mucinous adenocarcinoma. Among these patients, no positive N1 or N2 lymph node findings were observed. Moreover, the 5-year recurrence-free survival was still 100%, although the final pathologic results turned out to be IAC. INTERPRETATION: Patients undergoing limited resection of invasive LUAD misdiagnosed as AAH, AIS, or MIA by FS analysis showed excellent prognoses. Sublobar resection guided by FS diagnosis would be adequate for these underestimated cases of invasive LUAD.

Genetic-pathological prediction for timing and site-specific recurrence pattern in resected lung adenocarcinoma.

OBJECTIVES: We aimed to describe accurately the timing and site-specific recurrence pattern for surgical resected lung adenocarcinoma and develop genetic-pathological risk prediction models to guide individual postoperative surveillance strategies. METHODS: We retrospectively analysed radiological, pathological and sequencing data concerning 9 common oncogenic driver mutations from 1531 patients with resected lung adenocarcinoma between 2008 and 2015. The first recurrence site and time-to-recurrence were recorded. Independent risk factors were identified by multivariable regression analysis and consequently incorporated into prediction models. RESULTS: With a median follow-up of 53.2 months, postoperative recurrences were noted in 483 (31.5%) patients. Bone and brain recurrence tended to occur early (median 11.7 and 17.0 months, respectively) while thorax recurrence occurred later (median 22.2 months), which was validated across different tumour stages. EGFR mutation was an independent predictor for brain and bone recurrence and KRAS mutation for early recurrence. Both internal and external validation of the nomograms for brain and bone recurrence prediction showed optimal discrimination (concordance index: internal, 0.75 and 0.81, respectively; external, 0.77 and 0.84, respectively) and calibration. Recurrence occurred relatively evenly during the follow-up period in low-risk groups but mainly occurred within 2 years in high-risk groups. CONCLUSIONS: Unique biological differences exist among lung adenocarcinoma leading to distinct patterns of recurrence. These user-friendly genetic-pathological nomograms may help physicians to better stratify patients and make individual postoperative follow-up plans.

Combination of CD47 and CD68 expression predicts survival in eastern-Asian patients with non-small cell lung cancer.

OBJECTIVE: Recent studies have indicated that CD47, interacting with SIRP-α, conveys "don't eat me" signal in evasion of tumor cells and serves as a potential target for cancer immunotherapy. The purpose of this study was to investigate the clinical correlation of CD47 and uncover prognostic implications of CD47 and CD68 in non-small cell lung cancer (NSCLC). METHODS: The specimens from 384 patients with completely resected NSCLC were collected for immunohistochemical assays of CD47 and CD68. Cox multivariate proportion hazard analyses were conducted to confirm the independent prognostic value of CD47 and CD68. TCGA database and GSE37745 were used to identify the association between CD47 and immune cells. RESULTS: In 186 pairs of lung cancer and adjacent tissues, the RNA of CD47 was overexpressed in lung cancer tissues (P < 0.001). High expression of CD47 was associated with worse recurrence-free survival in RNA and protein level (P = 0.032 and P < 0.001, respectively). High expression of CD47 was significantly associated with large tumor size (P = 0.004), advanced pathologic TNM stage (P < 0.001), and histology (P = 0.003). Further analyses demonstrated that CD47 and CD68 predicted outcomes of patients independently. In addition, the expression of CD47 correlated with neutrophils, and did not correlated with B cells and CD4 + T cells in the TCGA database and GSE37745. CONCLUSION: Combined use of CD47 and CD68 exhibited excellent performance in predicting survival of patients with NSCLC. CD47 was a potential therapeutic target for immune therapy of lung cancer.

Systemic immune-inflammation index is a stage-dependent prognostic factor in patients with operable non-small cell lung cancer.

BACKGROUND: Immune function is a key component affecting tumor progression in patients with cancer. The purpose of this study was to identify the prognostic value of systemic immune-inflammation index (SII) in patients with non-small cell lung cancer (NSCLC) and the differences of its prognostic value in patients with distinct characteristics. METHODS: Patients with completely resected NSCLC were reviewed according to the eighth TNM classification of lung cancer. Patients were further categorized into the low- and high-SII groups. Cox proportional hazard analyses were performed to identify the independent prognostic factors. RESULTS: A total of 3984 patients with NSCLC were enrolled in this study. Kaplan-Meier analyses demonstrated that high SII was associated with worse recurrence-free survival (RFS) (P<0.001) and overall survival (OS) (P<0.001). Cox proportional hazard analyses revealed that SII was an independent risk factor for worse RFS (P=0.038) and OS (P=0.043). Further analyses demonstrated that the prognostic value of SII was observed only in patients with stage I disease (P<0.001), solid nodules (P=0.002), or adenocarcinoma (P<0.001). Sensitivity analyses using multiple imputation and competing risk analyses also confirmed similar results. CONCLUSIONS: SII was associated with worse survival independently, and its prognostic role was exhibited solely in NSCLC patients with stage I disease, solid nodules, and adenocarcinoma. This study helped us specify the target population for clinical use of SII.

Validation of the Novel International Association for the Study of Lung Cancer Grading System for Invasive Pulmonary Adenocarcinoma and Association With Common Driver Mutations.

INTRODUCTION: We aimed to validate the use of the novel grading system proposed by the International Association for the Study of Lung Cancer pathology committee for prognosis stratification of invasive pulmonary adenocarcinomas (ADCs) in Chinese patients. Correlations between the grading system, common driver mutations, and adjuvant chemotherapy (ACT) were also investigated. METHODS: From 2008 to 2016, the histologic patterns of a large cohort of 950 patients with invasive ADCs (stage I-III) were retrospectively analyzed and classified according to the proposed grading system. Subsequently, tumor grading was correlated with genetic data, ACT, and patient outcome. RESULTS: Compared with conventional predominant pattern-based groups, the novel grading system carried improved survival discrimination (area under the curve = 0.768 for recurrence-free survival and 0.775 for overall survival). The area under the curve was not further improved when incorporated lymphovascular invasion status. EGFR mutations (p < 0.001) were correlated with moderate grade, whereas KRAS mutations (p = 0.041) and ALK fusions (p = 0.021) were significantly more prevalent in poor grade. The reclassification of the grading system based on EGFR mutation status revealed excellent survival discrimination (p < 0.001). In particular, patients on stage Ib to III with novel high-grade ADCs had an improved prognosis with ACT. CONCLUSIONS: The novel International Association for the Study of Lung Cancer grading system is a practical and efficient discriminator for patient prognosis and should be part of an integrated pathologic-genetic subtyping to improve survival prediction. In addition, it may support patient stratification for aggressive adjuvant chemotherapy.

Segment Location and Ground Glass Opacity Ratio Reliably Predict Node-Negative Status in Lung Cancer.

BACKGROUND: Although selective mediastinal lymph node dissection based on lobe-specific nodal metastasis has been proposed for non-small cell lung cancer, controversy remains over its validity. We hypothesized that different segments within the same lobe might have different patterns of lymph node metastasis. METHODS: Data on 2749 invasive non-small cell lung cancer patients who underwent pulmonary resection with systematic lymph node dissection from April 2008 to December 2015 were retrospectively analyzed. The segment location and consolidation tumor ratio were identified using preoperative computed tomography scans. RESULTS: None of the 151 tumors with consolidation tumor ratio ≤ 0.5 had lymph node involvement. None of the 333 tumors located in apical segments had inferior mediastinal lymph node metastasis. When the analysis was limited to patients without hilar nodes involvement, only 7 out of 740 (0.9%) peripheral upper lobe tumors had inferior mediastinal lymph node metastasis. Interestingly, all these 7 tumors showed visceral pleural invasion. If hilar nodes were negative, superior mediastinal lymph node metastasis was not present for lower lobe ground glass opacity lesions. Among patients with left lower lobe tumors, if hilar nodes were negative, station 4L lymph node metastasis was not found in superior-segment or basal-segment tumors, and station 5/6 lymph node involvement was always absent in basal-segment tumors. CONCLUSIONS: Segment location, ground glass opacity proportion, and absence of hilar lymph nodes involvement are reliable predictors of node-negative status in specific mediastinal regions. Based on these findings, we propose a new selective mediastinal lymph node dissection strategy for non-small cell lung cancer.

Comparison of outcomes following segmentectomy or lobectomy for patients with clinical N0 invasive lung adenocarcinoma of 2 cm or less in diameter.

PURPOSE: Previous studies have reported similar survival between segmentectomy and lobectomy for patients with small-sized non-small cell lung cancer. However, part of those patients were with adenocarcinoma in situ or minimally invasive adenocarcinoma, which were considered to have a favorable prognosis. We compared survival outcomes of patients with clinical N0 invasive lung adenocarcinomas of no more than 2 cm who underwent segmentectomy or lobectomy. METHODS: Between June 1, 2008, and May 31, 2018, 1018 patients with clinical N0 invasive lung adenocarcinomas of no more than 2 cm in diameter on thin-section chest CT scans were retrospectively included in this study. Of them, 214 underwent segmentectomy and 804 underwent lobectomy. Propensity-score matching of preoperative factors, such as gender, age, smoking status, forced expiratory volume in 1 s predicted%, tumor's CT appearance, tumor size on CT scan and tumor location was used to compare survival outcomes of those patients receiving different surgical treatments. Cox proportional hazard regression model was used to identify independent prognostic factors. This study was approved by the Committee for Ethical Review of Research (Fudan University Shanghai Cancer Center IRB# 090977-1). Informed consent was waived because of the retrospective nature of this study. RESULTS: Average follow-up time was 42.5 months. Before matching, the lobectomy group had a shorter recurrence-free survival (P = 0.02), but similar overall survival (P = 0.60). After matching, no significant difference of overall survival or recurrence-free survival was found between the two groups (P = 0.70 and P = 0.40, respectively). CONCLUSIONS: Our results suggest that segmentectomy achieved similar recurrence-free and overall survival compared with lobectomy for patients with clinical N0 invasive lung adenocarcinomas of no more than 2 cm. Therefore, segmentectomy could be an alternative approach. These results need to be further validated by randomized trials.

Ground-glass opacity-featured lung adenocarcinoma has no response to chemotherapy.

PURPOSE: We aimed to investigate the treatment effect of chemotherapy on ground-glass opacity (GGO)-featured lung adenocarcinoma radiologically and pathologically. METHODS: This retrospective study included patients who met the following criteria: (1) presence of lung GGO lesions before chemotherapy for other concurrent malignancies; (2) underwent surgical resection of GGO-featured primary lung adenocarcinoma. The last computed tomography images before chemotherapy (CT1) and the last images before GGO resection (CT2) were reviewed to assess radiologic response. Specimens of the resected tumors were reviewed to evaluate the histopathologic response. Immunohistochemical staining of ki-67, caspase-3 and ß-gal was performed and compared between these tumors and a propensity score-matched (1:1) cohort of GGO-featured lung adenocarcinoma without prior chemotherapy. RESULTS: Forty-four patients with 55 GGO lesions were included. There were 20 mixed GGOs and 22 invasive adenocarcinomas. These patients all received at least three cycles of chemotherapy for other concurrent malignancies in breast, lung, cervix, ovary or rectum. Thirty-four (77%) patients received chemotherapy regimens that contained platinum, pemetrexed, paclitaxel, docetaxel or gemcitabine. The median interval between CT1 and CT2 was 10 months. Radiologically, all the GGO lesions either remained unchanged or enlarged. There was no chemotherapy-induced histopathologic response (necrosis, fibrosis or inflammation) in any of these tumors. The protein expression of ki-67, caspase-3 and ß-gal was comparable between GGO-featured lung adenocarcinoma with or without prior chemotherapy. CONCLUSION: GGO-featured lung adenocarcinoma has no response to chemotherapy. For these patients, chemotherapy should not be a treatment option.

Distinct Prognostic Factors in Patients with Stage I Non-Small Cell Lung Cancer with Radiologic Part-Solid or Solid Lesions.

INTRODUCTION: Recent studies have indicated that the presence of ground-glass opacity (GGO) components is associated with favorable survival. The purpose of this study was to reveal the prognostic value of GGO components and differences in prognostic factors for part-solid and solid lesions in invasive stage I NSCLC. METHODS: The cases of 2010 patients with completely resected invasive pathological stage I NSCLC were reviewed according to the eighth edition of the TNM classification. Patients were categorized into the pure-GGO, part-solid, and solid groups based on consolidation-to-tumor ratio. Cox multivariate proportional hazard analyses were conducted to identify independent prognostic factors in each group. RESULTS: Of the 2010 patients, 146 (7.3%) were in the pure-GGO group, 732 (36.4%) were in the part-solid group, and 1132 (56.3%) were in the solid group. Cox multivariate analyses revealed that GGO absence was a strong independent risk factor for worse recurrence-free survival (p < 0.001). For the pure-GGO group, there was no recurrence in spite of the invasive stage. For the part-solid group, visceral pleural invasion could not predict recurrence-free survival in general (p = 0.514) or in each tumor size group (for tumors size ≤1 cm, p = 0.664; for tumors size >1 to 2 cm, p = 0.456; for tumors size >2 to 3 cm, p = 0.900; and for tumors size >3 to 4 cm, p = 0.397). For the solid group, adenocarcinoma subtype was not a prognostic factor for recurrence-free survival in general (p = 0.162) or in each tumor size group (for tumors size ≤ 2 cm, p = 0.092; for tumors size >2 to 3 cm, p = 0.330; and for tumors size >3 to 4 cm, p = 0.885). CONCLUSIONS: The presence of GGO components was a strong predictor in patients with invasive pathological stage I NSCLC. Risk factors were distinct in the part-solid and solid groups. There was no prognostic value of visceral pleural invasion in the part-solid group. Adenocarcinoma subtype did not have prognostic value in the solid group.