Association of cholesterol and triglyceride levels with the recurrence of early-stage lung adenocarcinoma with micropapillary pattern

Introduction

Lung adenocarcinoma (LUAD), the most common histological type of primary lung cancer, has a rapid progression and a broad spectrum of radiological, molecular, and prognostic characteristics due to the complexity of the histological subtypes. Thus, the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) (1) proposed a classification scheme for LUAD consisting of five pathological subtypes: lepidic (favorable), acinar, papillary (intermediate), micropapillary, and solid (poor). The micropapillary pattern (MPP) refers to clusters of cells lacking central fibrovascular cores. Over the past decades, the global research into pathological MPP structures has gradually intensified. Studies have shown that the micropapillary subtype is a high-risk factor for distant metastasis and local recurrence in LUAD, and the presence of MPPs in LUAD is associated with distant micrometastasis (2-4). Moreover, studies indicate that a 1% presence of MPP is linked to postoperative local recurrence, occult lymph node metastasis, and poor prognosis (5-7).

High levels of cholesterol and triglyceride or the dysregulation of lipid metabolism may promote the progression of various cancers (8-11). Shao et al. reported that individuals with elevated serum total cholesterol (TC) levels are at a higher risk of lung cancer than are those with normal levels (12). Meanwhile, Ben Hassen et al. found that an increase in dietary cholesterol by 500 mg/day can increase the relative risk of lung cancer by 1.9% (13). In another study, FOXA3 knockdown or knockout blocked cholesterol biosynthesis and contributed to LUAD metastasis in vivo, which could be reversed by FOXA3 inhibitor (14). Due to the heterogeneity of lung cancer, as evidenced by the variety of findings in the literature, it remains difficult to draw definitive conclusions regarding the correlation between cholesterol or triglyceride levels and lung cancer. Contradictory findings among clinical studies and nonlinear relationships reported by in vitro or preclinical studies indicate that further research is needed in this area.

This study thus aimed to examine the potential link the levels of cholesterol and triglyceride and LUAD with MPP. We conducted a retrospective analysis using 261 LUAD patients with MPP and 658 LUAD patients without MPP to investigate the effects of cholesterol levels and triglyceride levels on metastasis and prognosis in LUAD with MPP. We present this article in accordance with the REMARK reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-118/rc).

Methods

Patient selection

We conducted a detailed study on patients with LUAD treated at the Thoracic Surgery Department of Jiangsu Provincial Cancer Hospital between 2015 and 2020. We screened 346 cases of postoperative pathology-confirmed LUAD with MPP and 783 cases of LUAD without MPP. All patients met the diagnostic criteria for lung cancer and underwent radical lung cancer surgery plus systematic distant lymphadenectomy, including dissection of the N1 and N2 groups. According to the TNM staging system (ninth edition) for lung cancer, we defined N0 as no regional lymph node metastasis, N1 as metastasis to the ipsilateral bronchial and/or hilar lymph nodes and intrapulmonary lymph nodes, and N2 as metastasis to the ipsilateral mediastinal and/or subcarinal lymph nodes. Our inclusion criteria included (I) LUAD with a preoperative tumor diameter ≤5 cm and (II) primary unifocal lesions. Meanwhile, the exclusion criteria were (I) multiple nodules, (II) progression of other cancers, and (III) a tumor diameter >5 cm. This study was approved by the Ethics Committee of Jiangsu Cancer Hospital (No. 2020129). This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. All patients’ informed consent forms were obtained.

Clinical data

We further collected the clinical and laboratory information from the enrolled patients. Clinical data encompassed sex, age, smoking history, history of alcohol consumption, history of hypertension, and history of diabetes. Laboratory data included the content of MPP, tumor size, cholesterol level, high-density lipoprotein (HDL) level, low-density lipoprotein (LDL) level, triglyceride level, and tumor location. Additionally, the data for the levels of triglyceride and cholesterol of patients were collected at three time points (1 week before surgery, 1 week after surgery, and 1 month after surgery), and the average values were recorded (Figure S1). We developed a new grading method based on the recommendations of the IASLC, applying a cutoff value of 20% for the micropapillary subtype of LUAD to divide patients into two groups as follows: MPP >20% was defined as the micropapillary-dominant group, while MPP ≥5% and ≤20% was defined as the micropapillary-low group.

Histological assessment

In terms of histological assessment, we collected slides stained postoperatively with hematoxylin and eosin (HE) from 346 patients with LUAD and MPP and performed pathological review according to the IASLC/ATS/ERS LUAD classification. We considered MPPs greater than 5% as indicative of the presence of this subtype, and two pathologists independently evaluated all LUAD specimens containing MPP. In cases of discrepancy in the evaluation results, a third pathological expert conducted a review.

Statistical analysis

For statistical analysis, we processed the data using SPSS 27.0 software (IBM Corp., Armonk, NY, USA). Quantitative data are described as the mean ± standard deviation (x¯±SD), and group comparisons were conducted using the t-test for two groups; categorical and ordinal data are presented as rates or percentages, with group comparisons conducted using the Chi-squared test of independence. To identify independent risk factors for the progression of patients with MPP, we included all factors into the multivariate logistic regression analysis, including MPP percentage, cholesterol level, triglyceride level, LDL level, and tumor size. Furthermore, Kaplan-Meier survival curves were conducted for progression-free survival (PFS) analysis, and cutoff values were selected using receiver operating characteristic (ROC) curve analysis. A P value ≤0.05 was considered statistically significant.

Results

Characteristics of patients in two cohorts

A total of 1,129 patients who underwent surgery between 2015 and 2020 were included in this study, with the specific screening process detailed in Figure 1. Among them, 261 patients were identified with MPP and 658 with non-MPP group. In the MPP group, 190 patients were diagnosed with MPP ranging from 5–20% and 71 patients were diagnosed with MPP greater than 20%. Postoperative progression occurred in 58 and 111 patients in the MPP and non-MPP group, respectively. Other baseline data were collected and are shown in Tables 1,2.

Figure 1 Screening process of MPP cohort and non-MPP cohort. MPP, micropapillary pattern.

Univariate and multiple logistic regression analysis in the MPP group

According to the recurrence and metastasis after surgery, the 261 patients with LUAD containing MPP were divided into a non-progression group (77.8%) and a progression group (22.2%). Univariate analysis of the 261 cases with MPP indicated that postoperative recurrence and metastasis were not significantly correlated with age (P=0.31), gender (P=0.69), smoking history (P=0.38), hypertension (P=0.80), diabetes (P=0.40), tumor primary location (P=0.24), LDL level ≥4.1 mmol/L (P=0.17), or HDL level <1 mmol/L (P=0.65); however, they were significantly associated with MPP (17.37% vs. 35.21%; P<0.001), cholesterol level (17.02% vs. 35.62%; P<0.001), tumor size (14.38% vs. 32.17%; P<0.001), and triglyceride level (13.24% vs. 32.00%, P<0.001) (Table 1). Meanwhile, we found that patients in the MPP group who experienced recurrence and metastasis often had higher levels of TC and percentage of MPP (Figure 2).

Figure 2 Comparison of cholesterol and triglyceride levels between postoperative progression and postoperative non progression patients in the two cohorts. (A) Comparison of cholesterol levels between postoperative progression and postoperative non-progression group. (B) Comparison of triglyceride levels between postoperative progression and postoperative non-progression group. (C) Comparison of MPP between postoperative progression and postoperative non-progression group, the Y axis represents the percentage of micropapillary content. P value is calculated using t-test. MPP, micropapillary pattern.

To identify independent risk factors for the progression of patients with MPP, we performed multivariate logistic regression analysis and the results showed that the independent risk factors for postoperative metastasis and recurrence in patients with LUAD with MPP were MPP >20% [odds ratio (OR) =2.327; 95% confidence interval (CI): 1.163–4.655; P=0.02], cholesterol level ≥5.20 mmol/L (OR =3.416; 95% CI: 1.574–7.540; P=0.002), triglyceride level ≥1.70 mmol/L (OR =0.481; 95% CI: 0.235–0.985; P=0.045), tumor size >3 cm (OR =3.366, 95% CI: 1.705–6.644; P<0.001) and location of lung cancer (OR =1.155, 95% CI: 0.910–1.492, P=0.26) (Table 3).

We further investigated the association of MPP content, cholesterol content, and triglyceride content with the prognosis of patients in MPP group. The survival analysis results showed that the micropapillary-dominant group (MPP >20%) often had shorter PFS as compared to the low-micropapillary group (5%≤ MPP ≤20%) (Figure 3). Interestingly, among patients with LUAD and MPP, the PFS of patients in the high-cholesterol group was significantly shorter than that in the low-cholesterol group, indicating that high cholesterol level and high triglyceride level are associated with poor postoperative prognosis in patients with LUAD (Figure 3A). Meanwhile, we observed a similar phenomenon in the overall survival between the two groups (Figure 3B).

Figure 3 Survival analysis of MPP cohort. (A) PFS analysis indicated that high cholesterol level and high triglyceride level are associated with poor postoperative prognosis in lung adenocarcinoma patients. (B) OS analysis indicated high cholesterol level and high triglyceride level are associated with poor postoperative prognosis in lung adenocarcinoma patients. MPP, micropapillary pattern; OS, overall survival; PFS, progression-free survival.

Prediction of the efficacy of postoperative adjuvant therapy

Additionally, we conducted an analysis of the sites for postoperative metastasis and recurrence in patients with LUAD and MPP, along with their cholesterol and triglyceride levels. Our result indicated that, overall, patients with LUAD and MPP tended to experience recurrence and metastasis primarily in the brain, lung, and bones. Furthermore, when the patients had high cholesterol levels, the sites of recurrence and metastasis were more likely to be the lungs (cholesterol <5.20 mmol/L: n=6; cholesterol ≥5.20 mmol/L: n=7, P=0.49) (Figure 4A,4B), while among those with a high triglyceride level, these processes were more likely to involve the lung (triglyceride <1.7 mmol/L: n=1; triglyceride ≥1.7 mmol/L: n=12, P=0.04) (Figure 4C,4D).

Figure 4 The sites for postoperative metastasis and recurrence in MPP cohort. The metastatic sites in patients of MPP cohort with (A) high cholesterol level, (B) low cholesterol level, (C) high triglyceride level. (D) The metastatic sites in patients of MPP cohort with low triglyceride level. MPP, micropapillary pattern.

As most patients in the MPP group had received postoperative adjuvant therapy, we selected patients with MPP who underwent chemotherapy or chemotherapy combined with targeted therapy after surgery for further analysis. We grouped them based on triglyceride level, cholesterol level, and the MPP and conducted a survival curve analysis. The results showed that among patients with high micropapillary pattern, those in the high-cholesterol group had a shorter PFS time as compared to those in the low-cholesterol group, suggesting that this subset of patients may have reduced sensitivity to postoperative adjuvant therapy (Figure 5A). In the low-micropapillary group, we did not observe a significant difference in PFS (Figure 5A). These results indicate that LUAD patients with high cholesterol and a significant MPP may receive poorer outcomes after postoperative adjuvant therapy.

Figure 5 Prediction of the efficacy of postoperative adjuvant therapy. (A) PFS analysis of patients who received postoperative adjuvant therapy. (B) ROC curve analysis to determine cut-off values. AUC was calculated. (C) Survival analysis results indicated that patients with CHOL-MPP value ≥2.584 and TG-MPP value ≥0.8065 exhibited significantly lower efficacy from postoperative adjuvant therapy. AUC, area under curve; CHOL, cholesterol; CI, confidence interval; MPP, micropapillary pattern; PFS, progression-free survival; ROC, receiver operating characteristic; TG, triglyceride.

Furthermore, to assess whether cholesterol and triglyceride levels could be used to predict the efficacy of postoperative treatment in patients with LUAD, we performed ROC curve analysis, with cholesterol and triglyceride levels yielding area under the curve values of 0.7149 and 0.7198, respectively (Figure 5B). In order to enhance the ability of cholesterol and triglyceride level to predict prognosis in patients MPP and facilitate risk stratification, we calculated ratios by multiplying cholesterol or triglyceride level with the MPP and conducted ROC curve analysis to determine the cutoff values. Survival analysis results indicated that patients with cholesterol-MPP value ≥2.584 and triglyceride-MPP value ≥0.8065 exhibited significantly lower efficacy from postoperative adjuvant therapy, accompanied by poorer prognoses (Figure 5C).

Univariate and multiple logistic regression analysis of the non-MPP group

Lipid metabolism has been reported to promote the progression of various cancers. However, it is not clear whether cholesterol and triglyceride levels are independent risk factors for a poor prognosis among patients with LUAD but no MPP. We further collected clinical data from 658 postoperative pathological cases of LUAD without MPP who underwent surgery between 2015 and 2020. Follow-up was conducted in January 2024, and multivariate analysis, and survival analysis were performed. The results indicated that in patients in the non-MPP group, cholesterol and triglyceride levels were not significantly correlated with recurrence or metastasis, and there was no statistical difference in PFS between the two groups (Tables 2,4; Figure 6).

Figure 6 Survival analysis of non-MPP cohort. (A) PFS analysis indicated that high cholesterol level and high triglyceride level are not associated with poor postoperative prognosis in non-MPP cohort. (B) OS analysis indicated high cholesterol level and high triglyceride level are not associated with poor postoperative prognosis in non-MPP cohort. MPP, micropapillary pattern; OS, overall survival; PFS, progression-free survival.

Discussion

In this study, we demonstrated that high cholesterol and triglyceride levels were independent prognostic factors and were negatively correlated with a recurrent-free prognosis in patients with LUAD and MPP but not in those without MPP. Furthermore, we found that the combination of cholesterol level or triglyceride level with MPP proportion could predict recurrence and that patients with MPP and a high cholesterol level may benefit from adjuvant therapy as compared to those with a low cholesterol. This indicates that cholesterol level can be used to optimize adjuvant strategy for patients with LUAD and MPP.

Dysregulation of lipid metabolism or hypercholesterolemia has been associated with the progression of various cancers based on both clinical and experimental studies. For instance, it was found that external cholesterol and triglyceride could directly activate the oncogenic Hedgehog pathway, while internal cholesterol could induce mTORC1 signaling (14,15). In addition, the cholesterol metabolism reprograms the tumor microenvironment across seven specialized microenvironments (16,17). Targeting cholesterol and triglyceride metabolism might not only exert antitumor effects in monotherapy and combination therapy but also mitigate the adverse effects associated with conventional tumor therapy as a therapeutic strategy for cancer. However, conclusions regarding the correlation between cholesterol or triglyceride levels and lung cancer remain elusive. Jiang et al. reported that abnormally higher or lower blood cholesterol levels increase the risk of lung cancer (18). However, higher cholesterol and triglyceride levels have been reported to be related to a lower risk of lung cancer, with a lower cholesterol level being associated worse survival in lung cancer (19,20). We believe that these conflicting results might be attributable to the heterogeneity of the pathology. In our study, cholesterol and triglyceride levels demonstrated different associations depending on the LUAD subtype. In order to further validate whether cholesterol and triglyceride levels are correlated with MPP proportion, we performed a series of statistical analyses and found these levels to be independent prognostic factors for patients with MPP. These results not only suggest a novel MPP-related prognostic factor, but also shed a light on the link between cholesterol or triglyceride metabolism and the aggressive behavior of the MPP subtype.

It is widely known that patients with LUAD and MPP have a poor prognosis regardless of stage due to the aggressive behavior of LUAD, the upgrade in stage, and lymphovascular invasion (19,21). Research on the mechanism of LUAD has identified that a loss of vascularity, cell-matrix contact, and fewer preserved intercellular junctions may contribute to the emergence of LUAD. Caso et al. found that patients with LUAD and MPP had increased chromosomal instability, higher tumor mutation burden, and more oncogenic signal pathway alterations as compared to patients with other histologic subtypes (22). In addition, Cheng et al. reported that even low proportion of MPP pattern was associated with poor prognosis and lymph node metastasis (23).

In their study on stage II–III LUAD, Cha et al. observed that in addition to lymph node metastases (N1 and N2 status), the results of multivariable analysis also indicated the presence of MPP to be a significant prognostic factor (24). Thus, optimizing the treatment of patients with LUAD and reducing the recurrence and metastasis remain critical issues. Lobectomy with lymphadenectomy is considered to be the standard treatment for cure among patients with stage IA LUAD. For those with the aggressive and invasive MPP subtype, the use of adjuvant therapy for patients with stage IA disease remains controversial due to the side effects. In our study, the high-risk patients—identified via the ratio of cholesterol or triglyceride levels and MPP proportion—as compared to the low-risk patients, were found to receive greater benefit from adjuvant therapy, indicating that this ratio might be a potential clinical biomarker for guiding the treatment of patients with LUAD and MPP. The JCOG0802 and CALGB 140503 trials demonstrated the superiority of segmentectomy over lobectomy in terms of overall survival for small-sized non–small cell lung cancer, but other research indicated that the occult presence of MPP pattern is associated with increased risk of relapse in patients treated with sublobar resection. Thus, the ratio of cholesterol or triglyceride levels to MPP proportions could aid considerably in risk prediction and treatment decision-making.

There are several limitations to this study. First, as we employed a retrospective, single-institution design, the thus results should be interpreted with caution, and further prospective research should be conducted to generate more reliable evidence. Second, as the patients were included from 2015 to 2020, a portion of them lacked information on spread-through-air-spaces status. Finally, EGFR status is a crucial important factor among patients with LUAD; however, owing to lack of gene sequence reports, we could not determine the correlation of EGFR status with MPP.

To conclude, a high cholesterol level in patients with LUAD and MPP was associated with patient prognosis, and the use of cholesterol level and MPP proportion in those with stage IA LUAD can achieve a better prediction of recurrence than can other commonly used methods. This finding may help guide the postoperative treatment strategy for those with early-stage LUAD. Moreover, our results raises questions as to whether patients with the aggressive pathological subtype of early-stage LUAD should be receive adjuvant therapy in prospective studies or in routine clinical practice.

Conclusions

In one word, the presence of abnormal TC and triglyceride levels in MPP + LUAD has a strong influence on patients’ prognosis, and utilization of TC/triglyceride levels and MPP proportion in stage IA LUAD can achieve a better prediction of recurrence than current classification in this cohort. This interesting result might provide an opportunity to guide the postoperative strategy of treatment for early stage LUAD. This observation raises the question whether the aggressive pathological subtype of early stage LUAD should be received adjuvant therapy in prospective studies or in routine clinical practice.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the REMARK reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-118/rc

Data Sharing Statement: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-118/dss

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-118/prf

Funding: This study was supported by the grants from the National Natural Science Foundation of China (grant Nos. 82073211, 82002434 and 82003106); The Project of Invigorating Health Care through Science, Technology and Education, Jiangsu Provincial Medical Innovation Team (No. CXTDA2017002); The Project of Invigorating Health Care through Science, Technology and Education, Jiangsu Provincial Medical Outstanding Talent (No. JCRCA2016001); and Young Talents Program of Jiangsu Cancer Hospital.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-118/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was approved by the Ethics Committee of Jiangsu Cancer Hospital (No. 2020129). This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. All patients’ informed consent forms were obtained.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Povsic TJ, Korjian S, Bahit MC, et al. Effect of Reconstituted Human Apolipoprotein A-I on Recurrent Ischemic Events in Survivors of Acute MI. J Am Coll Cardiol 2024;83:2163-74. [Crossref] [PubMed]
2. Nicholson AG, Tsao MS, Beasley MB, et al. The 2021 WHO Classification of Lung Tumors: Impact of Advances Since 2015. J Thorac Oncol 2022;17:362-87. [Crossref] [PubMed]
3. Yanagawa N, Shiono S, Abiko M, et al. The Clinical Impact of Solid and Micropapillary Patterns in Resected Lung Adenocarcinoma. J Thorac Oncol 2016;11:1976-83. [Crossref] [PubMed]
4. Li Y, Byun AJ, Choe JK, et al. Micropapillary and Solid Histologic Patterns in N1 and N2 Lymph Node Metastases Are Independent Factors of Poor Prognosis in Patients With Stages II to III Lung Adenocarcinoma. J Thorac Oncol 2023;18:608-19. [Crossref] [PubMed]
5. Wang Q, Song X, Zhang Y, et al. A pro-metastatic tRNA fragment drives aldolase A oligomerization to enhance aerobic glycolysis in lung adenocarcinoma. Cell Rep 2024;43:114550. [Crossref] [PubMed]
6. Wang W, Hu Z, Zhao J, et al. Both the presence of a micropapillary component and the micropapillary predominant subtype predict poor prognosis after lung adenocarcinoma resection: a meta-analysis. J Cardiothorac Surg 2020;15:154. [Crossref] [PubMed]
7. Yuan Y, Ma G, Zhang Y, et al. Presence of micropapillary and solid patterns are associated with nodal upstaging and unfavorable prognosis among patient with cT1N0M0 lung adenocarcinoma: a large-scale analysis. J Cancer Res Clin Oncol 2018;144:743-9. [Crossref] [PubMed]
8. Nitadori J, Bograd AJ, Kadota K, et al. Impact of micropapillary histologic subtype in selecting limited resection vs lobectomy for lung adenocarcinoma of 2cm or smaller. J Natl Cancer Inst 2013;105:1212-20. [Crossref] [PubMed]
9. Duan Y, Gong K, Xu S, et al. Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics. Signal Transduct Target Ther 2022;7:265. [Crossref] [PubMed]
10. Luo J, Yang H, Song BL. Mechanisms and regulation of cholesterol homeostasis. Nat Rev Mol Cell Biol 2020;21:225-45. [Crossref] [PubMed]
11. Yoon H, Shaw JL, Haigis MC, et al. Lipid metabolism in sickness and in health: Emerging regulators of lipotoxicity. Mol Cell 2021;81:3708-30. [Crossref] [PubMed]
12. Shao Y, Li W, Wen CP, et al. Dyslipidemia progression and increased lung cancer risk: a prospective cohort study. Eur J Epidemiol 2024;39:1363-71. [Crossref] [PubMed]
13. Ben Hassen C, Goupille C, Vigor C, et al. Is cholesterol a risk factor for breast cancer incidence and outcome? J Steroid Biochem Mol Biol 2023;232:106346. [Crossref] [PubMed]
14. Wang D, Cao Y, Meng M, et al. FOXA3 regulates cholesterol metabolism to compensate for low uptake during the progression of lung adenocarcinoma. PLoS Biol 2024;22:e3002621. [Crossref] [PubMed]
15. Guo J, Chen S, Zhang Y, et al. Cholesterol metabolism: physiological regulation and diseases. MedComm (2020) 2024;5:e476.
16. Ding X, Zhang W, Li S, et al. The role of cholesterol metabolism in cancer. Am J Cancer Res 2019;9:219-27.
17. Raccosta L, Fontana R, Corna G, et al. Cholesterol metabolites and tumor microenvironment: the road towards clinical translation. Cancer Immunol Immunother 2016;65:111-7. [Crossref] [PubMed]
18. Jiang W, Jin WL, Xu AM. Cholesterol metabolism in tumor microenvironment: cancer hallmarks and therapeutic opportunities. Int J Biol Sci 2024;20:2044-71. [Crossref] [PubMed]
19. Kim S, Kim G, Cho SH, et al. Association between total cholesterol levels and all-cause mortality among newly diagnosed patients with cancer. Sci Rep 2024;14:58. [Crossref] [PubMed]
20. Wu Y, Pu X, Wang X, et al. Reprogramming of lipid metabolism in the tumor microenvironment: a strategy for tumor immunotherapy. Lipids Health Dis 2024;23:35. [Crossref] [PubMed]
21. Zhou Y, Gao W, Xu Y, et al. Implications of different cell death patterns for prognosis and immunity in lung adenocarcinoma. NPJ Precis Oncol 2023;7:121. [Crossref] [PubMed]
22. Caso R, Sanchez-Vega F, Tan KS, et al. The Underlying Tumor Genomics of Predominant Histologic Subtypes in Lung Adenocarcinoma. J Thorac Oncol 2020;15:1844-56. [Crossref] [PubMed]
23. Cheng R, Hao Z, Qiu L, et al. The impact of postoperative adjuvant therapy on EGFR-mutated stage IA lung adenocarcinoma with micropapillary pathological subtypes. World J Surg Oncol 2024;22:235. [Crossref] [PubMed]
24. Cha MJ, Lee HY, Lee KS, et al. Micropapillary and solid subtypes of invasive lung adenocarcinoma: clinical predictors of histopathology and outcome. J Thorac Cardiovasc Surg 2014;147:921-928.e2. [Crossref] [PubMed]