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      Advancements in the diagnosis and treatment of sub‑centimeter lung cancer in the era of precision medicine (Review)

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          Abstract

          Lung cancer is the malignancy with the highest global mortality rate and imposes a substantial burden on society. The increasing popularity of lung cancer screening has led to increasing number of patients being diagnosed with pulmonary nodules due to their potential for malignancy, causing considerable distress in the affected population. However, the diagnosis and treatment of sub-centimeter grade pulmonary nodules remain controversial. The evolution of genetic detection technology and the development of targeted drugs have positioned the diagnosis and treatment of lung cancer in the precision medicine era, leading to a marked improvement in the survival rate of patients with lung cancer. It has been established that lung cancer driver genes serve a key role in the development and progression of sub-centimeter lung cancer. The present review aimed to consolidate the findings on genes associated with sub-centimeter lung cancer, with the intent of serving as a reference for future studies and the personalized management of sub-centimeter lung cancer through genetic testing.

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)
          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Comprehensive molecular profiling of lung adenocarcinoma

            Nikolaus Schultz (2015)
            Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.
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              Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020

              Wei Cao, Hong-Da Chen, Yi-Wen Yu … (2021)
              Background: Cancer is one of the leading causes of death globally, but its burden is not uniform. GLOBOCAN 2020 has newly updated the estimates of cancer burden. This study summarizes the most recent changing profiles of cancer burden worldwide and in China and compares the cancer data of China with those of other regions. Methods: We conducted a descriptive secondary analysis of the GLOBOCAN 2020 data. To depict the changing global profile of the leading cancer types in 2020 compared with 2018, we extracted the numbers of cases and deaths in 2018 from GLOBOCAN 2018. We also obtained cancer incidence and mortality from the 2015 National Cancer Registry Report in China when sorting the leading cancer types by new cases and deaths. For the leading cancer types according to sex in China, we summarized the estimated numbers of incidence and mortality, and calculated China's percentage of the global new cases and deaths. Results: Breast cancer displaced lung cancer to become the most leading diagnosed cancer worldwide in 2020. Lung, liver, stomach, breast, and colon cancers were the top five leading causes of cancer-related death, among which liver cancer changed from the third-highest cancer mortality in 2018 to the second-highest in 2020. China accounted for 24% of newly diagnosed cases and 30% of the cancer-related deaths worldwide in 2020. Among the 185 countries included in the database, China's age-standardized incidence rate (204.8 per 100,000) ranked 65th and the age-standardized mortality rate (129.4 per 100,000) ranked 13th. The two rates were above the global average. Lung cancer remained the most common cancer type and the leading cause of cancer death in China. However, breast cancer became the most frequent cancer type among women if the incidence was stratified by sex. Incidences of colorectal cancer and breast cancer increased rapidly. The leading causes of cancer death varied minimally in ranking from 2015 to 2020 in China. Gastrointestinal cancers, including stomach, colorectal, liver, and esophageal cancers, contributed to a massive burden of cancer for both sexes. Conclusions: The burden of breast cancer is increasing globally. China is undergoing cancer transition with an increasing burden of lung cancer, gastrointestinal cancer, and breast cancers. The mortality rate of cancer in China is high. Comprehensive strategies are urgently needed to target China's changing profiles of the cancer burden.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Mol Clin Oncol
                Journal ID (iso-abbrev): Mol Clin Oncol
                Journal ID (publisher-id): MCO
                Title: Molecular and Clinical Oncology
                Publisher: D.A. Spandidos
                ISSN (Print): 2049-9450
                ISSN (Electronic): 2049-9469
                Publication date Collection: April 2024
                Publication date (Electronic): 09 February 2024
                Publication date PMC-release: 09 February 2024
                Volume: 20
                Issue: 4
                Electronic Location Identifier: 28
                Affiliations
                [1 ]Department of Thoracic Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China
                [2 ]Department of Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China
                Author notes
                Correspondence to: Dr Jingwei Shi, Department of Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, Jiangsu 210008, P.R. China lzclzc0928foxmail.com shijingwei555@ 123456126.com

                Dr Zhengcheng Liu, Department of Thoracic Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, 321 Zhongshan Road, Nanjing, Jiangsu 210008, P.R. China lzclzc0928@ 123456foxmail.com

                Abbreviations: AAH, atypical adenomatous hyperplasia; AIS, adenocarcinoma in situ; ALK, anaplastic lymphoma kinase; BRAF, V-raf murine sarcoma viral oncogene homolog B1; CALGB, cancer and leukemia group B; CTR, consolidation-to-tumor ratio; EGFR, epidermal growth factor receptor; FISH, fluorescence in situ hybridization; GGN, ground glass nodules; IAC, invasive adenocarcinoma; KRAS, Kirsten rat sarcoma viral oncogene homolog; LCSG, Lung Cancer Study Group; mGGN, mixed GGN; MET, mesenchymal-epithelial transition factor; NCCN, National Comprehensive Cancer Network; OS, overall survival; pGGN, pure GGN; RATS, robot-associated thoracic surgery; RET, rearranged during transfection proto-oncogene; ROS1, ROS proto-oncogene 1 receptor tyrosine kinase; SCLC, small cell lung cancer; SN, solid nodules; VATS, video-associated thoracic surgery; VDT, volume doubling time

                Article
                Publisher ID: MCO-20-4-02726
                DOI: 10.3892/mco.2024.2726
                PMC ID: 10895471
                PubMed ID: 38414512
                SO-VID: c74bc9cd-cfc4-428e-9bdd-76fb8e04d3d0
                Copyright © Copyright: © Wang et al.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                Date received : 16 September 2023
                Date accepted : 10 January 2024
                Funding
                Funding: No funding was received.
                Categories
                Subject: Review

                Keywords: sub-centimeter lung cancer,gene mutation,pulmonary nodules,genetic testing
                Data availability:
                Keywords: sub-centimeter lung cancer, gene mutation, pulmonary nodules, genetic testing

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